WO2019058397A1

WO2019058397A1 - Formulation and development of topical or transdermal film

Info

Publication number: WO2019058397A1
Application number: PCT/IN2018/050619
Authority: WO
Inventors: Purnima D AMIN; Vishal KATARIA; Bhavna BASU; Kailas Kalicharan MORAVKAR
Original assignee: Jubeln Lifesciences, Pvt. Ltd.
Priority date: 2017-09-21
Filing date: 2018-09-21
Publication date: 2019-03-28

Abstract

The present disclosure provides a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water-soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water first soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5:1 to 80,000:1. The topical or transdermal film can be used for burn healing, wound healing, skin lightening, and skin rejuvenation. The present disclosure, also describes a convenient process for preparation of the topical film.

Description

FORMULATION AND DEVELOPMENT OF TOPICAL OR TRANSDERMAL FILM

FILED OF INVENTION

[001] The present disclosure discloses a topical or transdermal film comprising at least one active and at least one water-soluble polymer. The film of the present disclosure relates to a combination of water-soluble polymers along with desired active to achieve best results in terms of the effect. The present disclosure further relates to the continuous manufacturing of water soluble bio- polymers based multipurpose biofilm/bio-strips using twin-screw hot melt extrusion process. The present disclosure further relates to a process of continuous manufacturing of biofilms/bio-cubes for topical applications, such as burn healing, wound healing, rejuvenation of skin, personal care herbal bio-cubes for hygienic bath.

BACKGROUND OF INVENTION

[002] Skin is the largest organ of the human body and it performs a wide variety of functions including acting as a physical barrier against unwanted germs as well as an insulating cover against climatic variations. An example would be the protection rendered by the skin and skin -based pigments against harmful UV radiations. As a consequence, the skin sustains a significant damage due to wear-tear. In accordance over the last decade, skin care has burgeoned into a billion-dollar market, mainly fuelled by ever- increasing consumer demand and breakthrough scientific research.

[003] Traditional wound dressings include cotton wool, natural or synthetic bandages, and gauzes. Unlike the topical pharmaceutical formulations, these dressings are dry and do not provide a moist wound environment. Also, such semi-solid preparations are not very effective at adhering on the wound area as they rapidly absorb fluid, lose their rheological characteristics and become mobile.

[004] Modern wound management involving 'wet-healing' has suggested quicker healing times by maintaining moisture around the wound [RG Geronemus et al J. Dermatol. Surg. Oncol., 8(10), 850, 1982]. In light of the same, hydrogel formulations have been explored, however these too suffer from a number of drawbacks including poor skin adhesive property, exudate leakage, providing an ineffective barrier against pathogenic organisms and losing structural rigidity over time. Almost all the dressings which have hitherto been applied for the wet healing cannot be said to sufficiently satisfy the preferred characteristics for the medical treatment of wounds. For example, since semi-occlusive polyurethane films do not have a moisture absorbing property, there is a tendency for the wound to get dry and develop a crusta. Furthermore, rubber-elastomer based hydrocolloid dressings have poor transparency, making physical observation and treatment management difficult.

[005] Growth factors encourage the proliferation and/or differentiation of the cells in the tissue within and around the wound. Attempts have been made to expedite healing by introduction of various growth factors directly into the wound [Plast. Reconstr. Surg, Vol 88(2), 189-194, 1991 ; Dijke, P, et al. Biotechnology, 7, 793-798, 1989; G Schultz J. of Cellular Biochemistry, 45, 346- 352, 1991]. However, such growth factor containing formulations have several drawbacks. Over time, the enzymes produced from the patient's own tissue can degrade the gel and/or the growth factors. Further, the isolation and purification of the growth factor can decrease its biological activity. Finally, the cost of the isolated, purified growth factors is extremely high.

[006] Conventional techniques for ensuring adhesion of bandages to the wound involve fixing surgical tapes and use of medical pressure-sensitive adhesive sheets, magnetic bandages and pressure-sensitive adhesive bandages. Such formulations frequently suffer from problems of loss of adhesion upon water/exudate uptake and also inflammation of wounds caused by excessive applied pressure. Hence, there is a need for a wound healing formulation that would ensure fast healing using wet-healing technique, while having stable and soft adhesion around the wound.

[007] Another aspect of skin-care has revolved around the consumer's desire to obtain and/or maintain a youthful appearance. One manner of doing so is to remove (or reduce) wrinkles. Additionally, it is desirable to rejuvenate the skin by removing an outer layer of skin. There are known techniques for removing wrinkles by peeling the skin. Also, there are known methods for rejuvenating the skin. Unfortunately, all known techniques suffer from lack of efficacy and offer significant health risks to the patient.

[008] Peeling most or all of the outer layer of the skin is known method of rejuvenating the skin. Peeling can be achieved chemically, mechanically or photothermally. Chemical peeling is often carried out using trichloroacetic acid and phenol. An inability to control the depth of the peeling, possible pigmentary change and risk of scarring are among the problems associated with chemical peeling. The mechanical method is called transcutaneous pharoplasty and involves shaving off the outer layer of skin. Such surgical procedures often result in undesirable side effects, especially ectropion and scleral show. Moreover, transcutaneous blepharoplasty rarely eradicates all of the wrinkle lines. More recently, the use of CO2 laser light for skin rejuvenation also has led to undesirable side effects. For example, CO2 lasers have small spot size (3 mm or less), and thus their use causes valleys and ridges, particularly when resurfacing large areas. Also, it is difficult to control heat diffusion, and thus the resultant necrosis is difficult to predict and control. Additionally, scar tissue absorbs CO2 laser light differently than normal skin and thus may adversely impact such a treatment.

[009] Thus, it is apparent there is a need for a new method and device with which it is possible to produce efficient wound healing, wrinkle removal, skin rejuvenation and antiseptic properties. This apparatus would preferably be able to control the treatment parameters according to characteristics of the affected tissue and be easily tunable. The new method and device would preferably provide efficient would healing, wrinkle smoothing, skin rejuvenation and herbal properties with minimal side effects.

OBJECTIVE OF THE INVENTION:

[0010] It has been already perceived that industrially scalable, continuous manufacturing of biofilms/bio cubes using water soluble polymers and their combinations has never been disclosed earlier. Additionally, the manufacturing of such formulation in one-step is added advantage. Also, the product can be directly packaged after manufacturing.

[0011] The principle object of the present disclosure is to develop biofilms/bio cubes containing various actives by twin-screw hot melt extrusion as industrially scalable, continuous manufacturing process.

[0012] Another object of the present disclosure is to develop various pharmaceutical and nutraceutical compositions of these self-adhesive biofilms formulations like wound healing water soluble biofilm, skin rejuvenation water soluble biofilm, and bio cubes for herbal hygienic bath etc.

[0013] Additional object of present invention is to develop the novel bio-film platform which is cost effective, less energy intensive, single step, industrially scalable, less foot print, continuous manufacturing process and overcomes the process limitations of current formulations on wound healing and skin rejuvenation property.

SUMMARY OF THE INVENTION [0014] Pharmaceutical composition of biofilm/bio cubes developed by twin-screw hot melt extrusion process is disclosed here. Various drugs/medicaments/herbal actives/nutraceuticals can be added to the product formula and can be prepared by: Mixing all of the powdered ingredients in one container (except surface active agent and plasticizer), adding glycerol, surface active agent, and plasticizer, and then processing the mixture through twin-screw hot melt extrusion. A uniform product can be obtained with desired attributes of film thickness and film width by optimization of process, formulation and equipment's parameters (chilled roller unit for stretching the films). Optionally other pharmaceutical acceptable excipients can also be added. The obtained formulations can then be directly packed into containers and can be used for consumer use.

[0015] In an aspect of the present disclosure, there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; b) at least one first water-soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one first water-soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1.

[0016] In another aspect of the present disclosure, there is provided a process for the preparation of a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one water-soluble polymeric layer, the process comprising: a) obtaining the at least one first active; b) obtaining the at least one first water-soluble polymeric layer; c) contacting the at least one first active and the at least one water-soluble polymeric later to obtain a first mixture; d) extruding the first mixture to obtain the topical or transdermal film, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1.

BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS

[0017] Figure 1 illustrates a graph depicting percentage release of iodine from povidone iodine wound healing film, in accordance with an embodiment of the present disclosure.

[0018] Figure 2 illustrates the povidone iodine film retained on the membrane after a period of 2 hours, during a Franz diffusion cell study, in accordance with an embodiment of the present disclosure.

[0019] Figure 3 illustrates povidone iodine in donar cell after a period of 2 hours, during a Franz diffusion cell study, in accordance with an embodiment of the present disclosure. [0020] Figure 4 illustrates the anti-bacterial activity observed through betadine PI ointment (control), in accordance with an embodiment of the present disclosure.

[0021] Figure 5 illustrates the anti -bacterial activity of povidone iodine wound healing film, in accordance with an embodiment of the present disclosure.

[0022] Figure 6 illustrates the contact angle of a transdermal hydrophilic wound healing biofilm containing povidone iodine as active antiseptic, in accordance with an embodiment of the present disclosure.

[0023] Figure 7 illustrates the tensile strength of a topical antioxidant film containing cocoa/ chocolate powder prepared using double screw hot melt extrusion, in accordance with an embodiment of the present disclosure.

[0024] Figure 8 illustrates the field emission scanning electron microscopic (FE-SEM) study of the topical antioxidant film containing cocoa/ chocolate powder prepared using double screw hot melt extrusion, in accordance with an embodiment of the present disclosure.

[0025] Figure 9 illustrates the atomic force microscopic (AFM) study of a topical antioxidant film containing green tea prepared using double screw hot melt extrusion, in accordance with an embodiment of the present disclosure.

DETAILED DESCRIPTION OF THE INVENTION

[0026] Those skilled in the art will be aware that the present disclosure is subject to variations and modifications other than those specifically described. It is to be understood that the present disclosure includes all such variations and modifications. The disclosure also includes all such steps, features, compositions, and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any or more of such steps or features. Definitions

[0027] For convenience, before further description of the present disclosure, certain terms employed in the specification, and examples are delineated here. These definitions should be read in the light of the remainder of the disclosure and understood as by a person of skill in the art. The terms used herein have the meanings recognized and known to those of skill in the art, however, for convenience and completeness, particular terms and their meanings are set forth below.

[0028] The articles "a", "an" and "the" are used to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. [0029] The terms "comprise" and "comprising" are used in the inclusive, open sense, meaning that additional elements may be included. It is not intended to be construed as "consists of only".

[0030] Throughout this specification, unless the context requires otherwise the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated element or step or group of element or steps but not the exclusion of any other element or step or group of element or steps.

[0031] The term "including" is used to mean "including but not limited to". "Including" and "including but not limited to" are used interchangeably.

[0032] The term "at least one" is used to mean one or more and thus includes individual components as well as mixtures/combinations.

[0033] The term "labile active" and the term "first active" can be used interchangeably throughout the specification.

[0034] The term "non-labile active" and the term "second active" can be used interchangeably throughout the specification.

[0035] For the purposes of the present specification, the terms "wound healing agents", "antiseptics", "antioxidants", "antiaging agents", "whitening agents", "UV-protective agents", "skin conditioning agents", "analgesic agents", "bleaching agents", "desensitizing agents", "antifungal agents", and "anti-burn agents" refer to the well-known compounds of the respective categories recognized in the art.

[0036] Ratios, concentrations, amounts, and other numerical data may be presented herein in a range format. It is to be understood that such range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or subranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a temperature ranges of about 25-40 C should be interpreted to include not only the explicitly recited limits of about 25 C to about 40 C, but also to include sub-ranges, such as 25-30 C, 28-38 C, and so forth, as well as individual amounts, including fractional amounts, within the specified ranges, such as 25.2 C, and 38.5 C, for example.

[0037] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the disclosure, the preferred methods, and materials are now described. All publications mentioned herein are incorporated herein by reference.

[0038] The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended for the purposes of exemplification only. Functionally-equivalent products, compositions, and methods are clearly within the scope of the disclosure, as described herein.

[0039] Hot melt extrusion is an industrially feasible process for continuous manufacturing. A single-screw extruder consists of one rotating screw positioned inside a stationary barrel at the most fundamental level. The single-screw extrusion system has three zones with lots of disadvantages. It does not acquire the mixing capability of a twin-screw extruder and therefore is not the preferred approach for the production of most pharmaceutical formulations in industry. Moreover, a twin-screw extruder offers much greater versatility (process manipulation and optimization) in accommodating a wider range of pharmaceutical and nutraceutical formulations making it much more constructive.

[0040] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water- soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1. In another embodiment of the present disclosure, the at least one first water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.75: 1 to 400: 1. In yet another embodiment of the present disclosure, the at least one first water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.75: 1 to 100: 1.

[0041] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the topical or transdermal film optionally comprises a second water soluble polymeric layer.

[0042] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; b) at least one first water-soluble polymeric layer; and c) a second water soluble polymeric layer, wherein the first polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one first water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1.. In another embodiment of the present disclosure, the at least one first water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.75: 1 to 400: 1. In yet another embodiment of the present disclosure, the at least one first water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.75: 1 to 100: 1.

[0043] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the at least one first water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.75: 1 to 400: 1.

[0044] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the composition further comprises at least one additive selected from a group consisting of fragrance, flavor, plasticizer, stabilizer, preservative, surfactant, emulsifier, anti-caking agent, permeation enhancer, lubricant, adherent, dye, at least one second active, and combinations thereof.

[0045] In an embodiment of the present disclosure, there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; b) at least one first water-soluble polymeric layer; c) at least one additive selected from a group consisting of fragrance, flavor, plasticizer, stabilizer, preservative, surfactant, emulsifier, anti-caking agent, permeation enhancer, lubricant, adherent, dye, at least one second active, and combinations thereof, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one first water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1.

[0046] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the at least one first water-soluble polymeric layer comprises a water- soluble polymer selected from a group consisting of collagen derivatives, cellulose derivatives, pullulan, homo- and copolymers of vinyl pyrrolidone, homo- or copolymers of vinyl alcohol, homo- or copolymers of acrylic and/or methacrylic acids, and salts and esters thereof, starches and derivatives thereof, gums alginates, vegetable proteins, shellac, crotonic acid polymers, adipic acid polymers or carageenans, and combinations thereof.

[0047] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the at least one first water-soluble polymeric layer comprises a water- soluble polymer selected from a group consisting of collagen derivatives, cellulose derivatives, such as nitrocellulose, cellulose ether, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, pullulan, homo- and copolymers of vinyl pyrrolidone, such as PVP, PVP/PVA copolymers, homo- or copolymers of vinyl alcohol, such as polyvinyl alcohol, homo- or copolymers of acrylic and/or methacrylic acids, and salts and esters thereof, starches and derivatives thereof, gums such as xanthan gum, gum arabica, guar gum, carob bean gum, cellulose gum, alginates, vegetable proteins, shellac, crotonic acid polymers, adipic acid polymers or carageenans, and combinations thereof. In another embodiment of the present disclosure, the at least one first water-soluble polymeric layer comprises a combination of water soluble polymer maltodextrin, hydroxy propyl cellulose EF, and PVA copolymer.

[0048] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the at least one first active is selected from the group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV -protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti-burn agents, and combinations thereof.

[0049] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the at least one first active may be any pharmaceutical and cosmetic ingredients including, but not limited to, wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV-protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti-burn agents, and combinations thereof.

[0050] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water- soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1 , and wherein the at least one first active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV-protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti- burn agents, and combinations thereof, and wherein the at least one first active is an antiseptic, and wherein the antiseptic is zinc oxide. In another embodiment of the present disclosure, zinc oxide has a weight percentage in a range of 35-45% with respect to the film. [0051] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water- soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1, and wherein the at least one first active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV-protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti- burn agents, and combinations thereof, and wherein the at least one first active is an antioxidant, and wherein the antioxidant is green tea powder/green tea extract. In another embodiment of the present disclosure, green tea extract/green tea powder has a weight percentage in a range of 15- 25% with respect to the film.

[0052] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water- soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1, and wherein the at least one first active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV-protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti- burn agents, and combinations thereof, and wherein the at least one first active is an antiaging agent, and wherein the antiaging agent is cocoa powder. In another embodiment of the present disclosure, the antiaging agent is chocolate powder. In yet another embodiment of the present disclosure, cocoa powder has a weight percentage in a range of 15-25% with respect to the film.

[0053] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water- soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1, and wherein the at least one first active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV-protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti- burn agents, and combinations thereof, and wherein the at least one first active is wound healing agent, and wherein the wound healing agent is povidone iodine. In another embodiment of the present disclosure, povidone iodine has a weight percentage in a range of 5-15% with respect to the film.

[0054] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water- soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1, and wherein the at least one first active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV -protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti- burn agents, and combinations thereof, and wherein the at least one first active is whitening agent, and wherein the whitening agent is undecylenoyl phenylalanine. In another embodiment of the present disclosure, undecylenoyl phenylalanine has a weight percentage in a range of 0.1-2% with respect to the film. In yet another embodiment of the present disclosure, the whitening agent is a combination of vitamin A palmitate and hyaluronic acid having a combined weight percentage in a range of 1-4% with respect to the film.

[0055] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water- soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1, and wherein the at least one first active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV -protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti- burn agents, and combinations thereof, and wherein the at least one first active is skin conditioning agent, and wherein the skin conditioning agent is an anti-wrinkle agent dipalmitoyl hydroxyproline having a weight percentage in a range of 0.5-2% with respect to the film. In another embodiment of the present disclosure, the skin conditioning agent is an anti-acne agent adapalene having a weight percentage in a range of 0.05-1% with respect to the film. In yet another embodiment of the present disclosure, the skin conditioning agent is a hair removal agent calcium thioglycolate having a weight percentage in a range of 20-30% with respect to the film.

[0056] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water- soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1, and wherein the at least one first active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV -protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti- burn agents, and combinations thereof, and wherein the at least one first active is an analgesic agent, and wherein the analgesic agent is diclofenac sodium. In another embodiment of the present disclosure, diclofenac sodium has a weight percentage in a range of 5-20% with respect to the film.

[0057] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water- soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1, and wherein the at least one first active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV -protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti- burn agents, and combinations thereof, and wherein the at least one first active is a bleaching agent, and wherein the bleaching is hydrogen peroxide (30%). In another embodiment of the present disclosure, hydrogen peroxide (30%) has a weight percentage in a range of 5-20% with respect to the film.

[0058] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water- soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1, and wherein the at least one first active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV -protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti- burn agents, and combinations thereof, and wherein the at least one first active is a desensitizing agent, and wherein the desensitizing agent is potassium nitrate. In another embodiment of the present disclosure, potassium nitrate has a weight percentage in a range of 2-20% with respect to the film.

[0059] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water- soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1, and wherein the at least one first active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV -protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti- burn agents, and combinations thereof, and wherein the at least one first active is an antifungal agent, and wherein the antifungal agent is ciclopirox. In another embodiment of the present disclosure, ciclopirox has a weight percentage in a range of 2-20% with respect to the film.

[0060] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one first water- soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1, and wherein the at least one first active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV -protective agents, skin conditioning agents, analgesic agents, bleaching agents, antiseptic agents, desensitizing agents, antifungal agents, anti- burn agents, and combinations thereof, and wherein the at least one first active is a wound healing agent, and wherein the wound healing agent is chitosan having a weight percentage in a range of 1-10% with respect to the film. [0061] The at least one first active of the present disclosure can be selected from polyphenol actives, green tea extracts, white tea extracts, red tea extracts, black tea extracts, licorice extracts, phytosphingosine, ethylbisiminomethylguaiacol manganese chloride, povidone iodine, cocoa powder, chitosan, adapalene, calcium thioglycolate, ciclopirox, potassium nitrate, hydrogen peroxide, hyaluronic acid, vitamin A palmitate, zinc oxide, diclofenac sodium, Dipalmitoyl hydroxyproline, undecylenoyl phenylalanine, white birch extract, hinokitiol, coffee extract, hoelen mushroom extract, ascorbic acid, siegesbeckia, rosemary extract, silymarin, boswellia extract, ubiquinone, retinoids, resveratrol, potassium cholesterol sulfate, protease enzymes, lipase enzymes, apigenin, vitamin E, grape seed extract, lutein, licochalcone, luteolin, ursolic acid, centella asiatica extract, ximenynic acid, ferulic acid, amentoflavone, dihydroxyacetone, conjugated Hnoleate, salicylic acid, 1, 3-beta glucan, triclosan, and combinations thereof. The effective amounts of the active as used in the system of the present application will vary depending on the active selected and the pharmaceutical/cosmetic benefit desired, but ordinarily will be within the range of known active concentrations for the selected material, or in some cases, may be lower because of the greater retained activity. Overall, as a guideline, the ranges will typically be from 0.001% to 60% by weight of the total composition. In one embodiment, the effective amounts of povidone-iodine are from 0.5% to 15%, preferably from 0.5 to 0.12% and most preferably from 0.5 to 0.10%. As another example, the effective amounts of antioxidants such as from green tea extracts, are from 0.001% to 2%. In another embodiment of the present disclosure the antioxidant ranges from 0.01 % to 1.5%. In yet another embodiment of the present disclosure, the antioxidant ranges from 0.1 % to 1 %. It should be noted that the actives may be used in combination in the system of the present disclosure as long as each active does not interfere with the stability of the other actives.

[0062] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the first active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV-protective agents, skin conditioning agents, analgesic agents, bleaching agents, desensitizing agents, antifungal agents, anti-burn agents, and combinations thereof.

[0063] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the second water-soluble polymeric layer comprises a water-soluble polymer selected from a group consisting of polyethylene glycol, hydrophilic siloxysilicates, hydrophilic silicone polyacrylates, and combinations thereof.

[0064] In an embodiment of the present disclosure, there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV- protective agents, skin conditioning agents, analgesic agents, bleaching agents, desensitizing agents, antifungal agents, anti-burn agents, and combinations thereof; b) at least one first water- soluble polymeric layer selected from a group consisting of collagen derivatives, cellulose derivatives selected from nitrocellulose, cellulose ether, carboxymethyl cellulose, hydroxymethyl cellulose, or hydroxypropyl cellulose, pullulan, homo- and copolymers of vinyl pyrrolidone selected from PVP or PVP/PVA copolymers, homo- or copolymers of vinyl alcohol selected from polyvinyl alcohol, homo- or copolymers of acrylic and/or methacrylic acids, and salts and esters thereof, starches and derivatives thereof, gums selected from xanthan gum, gum arabica, guar gum, carob bean gum, cellulose gum, alginates, vegetable proteins, shellac, crotonic acid polymers, adipic acid polymers or carageenans, and combinations thereof; c) a second water-soluble polymeric layer selected from a group consisting of polyethylene glycol, hydrophilic siloxysilicates, hydrophilic silicone polyacrylates, and combinations thereof; and d) at least one additive selected from a group consisting of fragrance, flavor, plasticizer, stabilizer, preservative, surfactant, emulsifier, anti-caking agent, permeation enhancer, lubricant, adherent, dye, and at least one second active, wherein the first polymeric layer forms a polymer matrix and the at least one first active, and the second active is dispersed throughout the polymer matrix, and the at least one first water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1.

[0065] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, comprising: a) a composition comprising at least one first active having weight percentage in a range of 0.001 - 60% with respect to the film; and b) at least one first water-soluble polymeric layer having weight percentage in the range of 30 - 80% with respect to the film, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix.

[0066] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV- protective agents, skin conditioning agents, analgesic agents, bleaching agents, desensitizing agents, antifungal agents, anti-burn agents, and combinations thereof, having weight percentage in a range of 0.001 - 60% with respect to the film; and b) at least one first water-soluble polymeric layer selected from a group consisting of collagen derivatives, cellulose derivatives, such as nitrocellulose, cellulose ether, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose; pullulan, homo- and copolymers of vinyl pyrrolidone such as PVP or PVP/PVA copolymers; homo- or copolymers of vinyl alcohol, such as polyvinyl alcohol, homo- or copolymers of acrylic and/or methacrylic acids, and salts and esters thereof, starches and derivatives thereof, or gums such as xanthan gum, gum arabica, guar gum, carob bean gum, cellulose gum, alginates, vegetable proteins, shellac, crotonic acid polymers, adipic acid polymers or carageenans, and combinations thereof, having weight percentage in a range of 30 - 80% with respect to the film, wherein the first polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one first water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1.

[0067] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the topical or transdermal film optionally comprising a second water- soluble polymeric layer having weight percentage in a range of 2 - 50% with respect to the film.

[0068] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, comprising: a) a composition comprising at least one first active having weight percentage in a range of 0.001 - 60% with respect to the film; and b) at least one first water-soluble polymeric layer having weight percentage in the range of 30 - 80% with respect to the film; c) a second water-soluble polymeric layer having weight percentage in a range of 2 - 50% with respect to the film, wherein the first polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix.

[0069] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, comprising: a) a composition comprising at least one first active selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV-protective agents, skin conditioning agents, analgesic agents, bleaching agents, desensitizing agents, antifungal agents, anti-burn agents, and combinations thereof, having weight percentage in a range of 0.001 - 60% with respect to the film; and b) at least one first water-soluble polymeric layer comprises a water-soluble polymer selected from a group consisting of collagen derivatives, cellulose derivatives, e.g., nitrocellulose, cellulose ether, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose; pullulan, homo- and copolymers of vinyl pyrrolidone, e.g., PVP or PVP/PVA copolymers; homo- or copolymers of vinyl alcohol, such as polyvinyl alcohol, homo- or copolymers of acrylic and/or methacrylic acids, and salts and esters thereof, starches and derivatives thereof, or gums such as xanthan gum, gum arabica, guar gum, carob bean gum, cellulose gum, alginates, vegetable proteins, shellac, crotonic acid polymers, adipic acid polymers or carageenans, and combinations thereof, having weight percentage in the range of 30 - 80% with respect to the film; and c) a second water-soluble polymeric layer selected from a group consisting of polyethylene glycol, hydrophilic siloxysilicates, hydrophilic silicone polyacrylates, and combinations thereof, having weight percentage in a range of 2 - 50% with respect to the film, wherein the first polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one first water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1.

[0070] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the composition further comprises at least one additive selected from a group consisting of: (a) fragrance having weight percentage in a range of 0-2% with respect to the film, and selected from a group of floral fragrances comprising essential oils such as essential rose oil or rose water, lemongrass, patchouli, sage, cypress and cedar-wood, wild geranium, spearmint, tea tree, juniper, aloe, cucumber, musk, , and combinations thereof; (b) flavor having weight percentage in a range of 0-2% with respect to the film, and selected from a group consisting of menthol, vanilla, orange, cocoa, citric acid, butter scotch, pista, strawberry, aloe vera, amla, neem extract, cucumber, and combinations thereof; plasticizer having weight percentage in a range of 2 - 20% with respect to the film, and selected from a group consisting of sorbitol, glycerine, propylene glycol, diisobutyl adipate, acetyl tri-n-butyl citrate, di(2-ethyl hexyl) azelate, 2-ethyl hexyl diphenyl phosphate, diisoctyl isophthalate, isooctyl benzyl phthalate, butyl stearate, tri-2- ethyl hexyl trimellitate, N-octyl neopentanoate, diisostearyl malate, glycerol, and colloidal fumed silica; (c) stabilizer having weight percentage in a range of 0.001- 0.05% with respect to the film, and selected from a group consisting of natural, artificial gums, and combinations thereof; (d) preservative having weight percentage in a range of 0.001-0.05% with respect to the film, and selected from a group consisting of vitamin C, vitamin E, butylated hydroxytoluene (BHT), butylated hydroxy anisole (BHA), benzoates, parabens, sorbate, citric acid, polyphosphates, ethylenediaminetetraacetic acid (EDTA), sodium chloride, lemon, neem oil, honey, propionates, nitrites, and combinations thereof ; (e) surfactant having weight percentage in a range of 0.01-1% with respect to the film, and selected from a group consisting of sodium lauryl sulphates, and combinations thereof; (f) emulsifier having weight percentage in a range of 0.001-1% with respect to the film, and selected from a group consisting of emulsifying wax, polysorbate 80, tween 20, tween 80, and combinations thereof; (g) dye having weight percentage as much as is necessary, and is selected from a group consisting of xanthine, pyrazolone, indigoid, triphenyl methane, and combinations thereof; (h) at least one second active having weight percentage in a range of 10- 80% with respect to the film, and selected from a group consisting of monosaccharides, disaccharides, polysaccharides, carbohydrates selected from a group consisting of lactose, dextrose, starch, mannitol, maltose, sucrose, and combinations thereof, and combinations thereof; (i) at least one anti-caking agent having a weight percentage of 0.5-10% with respect to the film, and selected from a group consisting of microcrystalline cellulose (MCC 101), sodium lauryl sulfate, silicon dioxide, tween, polyoxyethylene alkylethers, benzethonium chloride, dibutyl tartrate, and combinations thereof, j) at least one lubricant having a weight percentage of 0.5-10% with respect to the film, and selected from a group consisting of talc, magnesium silicate, stearic acid, , sucrose esters, and combinations thereof (j) at least one adherent having a weight percentage of 0.5-52% with respect to the film, and selected from a group consisting of carboxymethyl cellulose sodium, sodium alginate, agar, xantham gum, carrageenan, locust bean gum, guar gum, gum tragacanth, and combinations thereof, and (k) at least one penetration enhancer having a weight percentage in a range of 0.1 - 30% in the film, and selected from a group consisting of a- hydroxyacids, fatty acid esters and amides thereof, fatty alcohols, fatty acids and esters of glycerol, saturated polyglycerides, decylmethylsulfoxide, dimethyl sulfoxide (DMSO), pyrrolidones, salicyilic acid, lactic acid, isopropyl myristate, dimethylformamide, dimethylacetamide, sodium dodecylsulfate, phospholipids, mixtures of oleic acid and 2-(2-ethoxyethoxy)-ethanol, fatty acids, enzymes, compounds made from urea, alkylsulfoxides, and combinations thereof.

[0071] In an embodiment of the present disclosure there is provided a topical or transdermal film comprising: a) a composition comprising at least one first active selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV- protective agents, skin conditioning agents, analgesic agents, bleaching agents, desensitizing agents, antifungal agents, anti-burn agents, and combinations thereof, having weight percentage in a range of 0.001 - 60% with respect to the film; and b) at least one first water-soluble polymeric layer comprises a water-soluble polymer selected from a group consisting of collagen derivatives, cellulose derivatives, e.g., nitrocellulose, cellulose ether, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose; pullulan, homo- and copolymers of vinyl pyrrolidone, e.g., PVP or PVP/PVA copolymers; homo- or copolymers of vinyl alcohol, such as polyvinyl alcohol, homo- or copolymers of acrylic and/or methacrylic acids, and salts and esters thereof, starches and derivatives thereof, or gums such as xanthan gum, gum arabica, guar gum, carob bean gum, cellulose gum, alginates, vegetable proteins, shellac, crotonic acid polymers, adipic acid polymers or carageenans, and combinations thereof, having weight percentage in the range of 30 - 80% with respect to the film; c) a second water-soluble polymeric layer comprises a water-soluble polymer selected from a group consisting of polyethylene glycol, hydrophilic siloxysilicates, hydrophilic silicone polyacrylates, and combinations thereof, having weight percentage in a range of 2 - 50% with respect to the film; and d) at least one additive selected from a group consisting of: (i) fragrance having weight percentage in a range of 0-2% with respect to the film, and selected from a group consisting of floral fragrances, essential oils such as essential rose oil or rose water, lemongrass, patchouli, sage, cypress and cedar-wood, wild geranium, spearmint, tea tree, juniper, aloe, cucumber, musk,, and combinations thereof; (ii) flavor having weight percentage in a range of 0-2% with respect to the film, and selected from a group consisting of menthol, vanilla, orange, cocoa, citric acid, butter scotch, pista, strawberry, aloe vera, amla, neem extract, cucumber, and combinations thereof; (iii) plasticizer having weight percentage in a range of 2 - 15% with respect to the film, and selected from a group consisting of sorbitol, glycerine, propylene glycol, diisobutyl adipate, acetyl tri-n-butyl citrate, di(2-ethyl hexyl) azelate, 2-ethyl hexyl diphenyl phosphate, diisoctyl isophthalate, isooctyl benzyl phthalate, butyl stearate, tri-2-ethyl hexyl trimellitate, N- octyl neopentanoate, diisostearyl malate, glycerol, and colloidal fumed silica; (iv) stabilizer having weight percentage in a range of 0.001- 0.05% with respect to the film, and selected from a group consisting of natural, artificial gums, and combinations thereof; (v) preservative having weight percentage in a range of 0.001-0.05% with respect to the film, and selected from a group consisting of vitamin C, vitamin E, butylated hydroxytoluene (BHT), butylated hydroxy anisole (BHA), benzoates, parabens, sorbate, citric acid, polyphosphates, ethylenediaminetetraacetic acid (EDTA), sodium chloride, lemon, neem oil, honey, propionates, nitrites, and combinations thereof ; (vi) surfactant having weight percentage in a range of 0.01-1% with respect to the film, and selected from a group consisting of benzoates, sodium lauryl sulphates, and combinations thereof; (vii) emulsifier having weight percentage in a range of 0.001-1% with respect to the film, and selected from the group consisting of emulsifying wax, polysorbate 80, tween 20, tween 80, and combinations thereof; (viii) dye having weight percentage as much as is necessary, and selected from a group consisting of xanthine, pyrazolone, indigoid, triphenyl methane, and combinations thereof; and (ix) at least one second active having weight percentage in a range of 10-80% with respect to the film, and selected from a group consisting of monosaccharides, disaccharides, polysaccharides, and carbohydrates selected from a group consisting of lactose, dextrose, starch, mannitol, maltose, sucrose, and combinations thereof; and combinations thereof, (ix) at least one anti-caking agent having a weight percentage of 0.5-10% with respect to the film, and selected from the group consisting of microcrystalline cellulose (MCC 101), sodium lauryl sulfate, silicon dioxide, tween, polyoxyethylene alkylethers, benzethonium chloride, dibutyl tartrate, cocoa powder, and combinations thereof, (x) at least one lubricant having a weight percentage of 0.5- 10% with respect to the film, and selected from a group consisting of talc, magnesium silicate, stearic acid, sucroesters, sucrose esters, and combinations thereof (xi) at least one adherent having a weight percentage of 0.5-52% with respect to the film, and selected from the group consisting of carboxymethyl cellulose sodium, sodium alginate, agar, xantham gum, carrageenan, locust bean gum, guar gum, gum tragacanth, and combinations thereof, and (xii) at least one penetration enhancer having a weight percentage of 0.1 - 30% in the film, and selected from the group consisting of a-hydroxyacids, fatty acid esters and amides thereof, fatty alcohols, fatty acids and esters of glycerol, saturated polyglycerides, decylmethylsulfoxide, pyrrolidones, salicyilic acid, lactic acid, isopropyl myristate, dimethylformamide, dimethylacetamide, sodium dodecylsulfate, phospholipids, mixtures of oleic acid and 2-(2-ethoxyethoxy)-ethanol, fatty acids, enzymes, compounds made from urea, alkylsulfoxides, and combinations thereof; wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer has a weight that is at least 0.5 times the weight of at least one first active but not more than 80,000 times the weight of the at least one first active. In another embodiment of the present disclosure, the at least one first water-soluble polymeric layer comprises a combination of maltodextrin, hydroxy propyl cellulose EF, and PVA, the plasticizer is selected from a group consisting of sorbitol, glycerine, propylene glycol, and combinations thereof.

[0072] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the film has: (a) thickness in the range of 0.02 - 0.2 mm for transdermal film and thickness in the range of 0.2 - 5mm; (b) folding endurance of topical film in the range of 1-2; (c) tensile strength in the range of 1-10 N/m²; (d) percentage elongation in the range of 10-60%; (e) surface pH in the range of should be 5 - 6.5; and (f) contact angle in the range of 0-90 degree.

[0073] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the film is transformed into a product selected from the group consisting of topical or transdermal patch, mask, and biocube. In another embodiment of the present disclosure the biocube is directly extruded into any desired shape using hot melt extrusion technique.

[0074] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the patch on application onto the skin of a subject, followed by dissolution of the at least one water-soluble polymeric layer, leads to the transfer of the at least one first active to skin. In another embodiment of the present disclosure the transfer of the at least one first active to skin is beneficial in skin repair and rejuvenation.

[0075] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the film is used as a topical or transdermal product for burn healing, wound healing, skin lightening, and skin rejuvenation.

[0076] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the biocube is used as a bath product.

[0077] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the film can be used to yield numerous benefits. The water-soluble polymeric film incorporating an active may be applied to the skin and adhered using the simple tap water. The film therefore serves as an excellent means of delivering active to the skin. The film carrying the active may be made in any shape or size to accommodate the treatment/or personnel care needed. Therefore, the appropriately shaped film/ or cubes could be used for spot treatment or as a mask for a larger area of treatment/or personnel care. A specific example is the use of the system for delivering actives that provide a whitening effect. Rather than application of a whitening composition to an entire skin surface, a film patch can deliver whitening agents directly to age spots or discolored areas. For this purpose, whitening agents such as nano-curcumin, kojic acid, hydroquinone, ascorbic acid, magnesium ascorbyl phosphate, and ascorbyl glucoside may be incorporated into the film and adhere using simple tap water to transfer the whitening agent to the areas of the skin where whitening is desired.

[0078] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the film may be used on various parts of the skin such as corners of the eyes, along the upper lips, and other areas in need of an intense direct treatment, for example, with an anti-aging or anti- wrinkle treatment. In an embodiment of the present disclosure, the use of the present inventive system is for spot wrinkle treatment. A patch containing one or more anti- wrinkle actives can be applied directly to the area to be treated, for example, on crow's feet, under eyes, around the lips, neck area, deep furrows on the forehead, and brow area. Examples of first actives, anti- wrinkle or anti-aging actives include cocoa powder, retinoids, vitamin C, curcumin, lipoic acids, resveratrol, 2- hydroxyalkanoic acids, prostaglandins, ceramides and their derivatives.

[0079] In an embodiment of the present disclosure there is provided a process for the preparation of a topical or transdermal film comprising: a) a composition comprising at least one first active; b) at least one first water-soluble polymeric layer, the said process comprising the steps of a) obtaining the at least first active; b) obtaining the at least one first water-soluble polymeric layer; c) contacting the at least one first active and the at least one first water-soluble polymeric later to obtain a first mixture; d) extruding the first mixture to obtain the topical or transdermal film, wherein the polymeric layer forms a polymer matrix and the at least one active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer has a weight that is at least 0.5 times the weight of at least one first active but not more than 80,000 times the weight of the at least one active.

[0080] In an embodiment of the present disclosure there is provided a process for the preparation of a topical or transdermal film as described herein, wherein contacting the at least one first active and the at least one water-soluble polymeric later to obtain a first mixture is carried out in a kneading zone at a temperature in the range of 45-115 °C.

[0081] In an embodiment of the present disclosure there is provided a process for the preparation of a topical or transdermal film as described herein, wherein extruding the first mixture is done by hot melt extrusion process-flow comprising the following parts: a) an opening/hopper through which the at least one first active and the at least one water-soluble polymer layer enter the barrel or alternatively these may be continuously supplied in a controlled manner by one or more external feeder; b) a conveying section comprising the barrel and the screw(s) that transport, and where applicable, mix/homogenize the first mixture; c) an orifice/die for shaping the first mixture as it leaves the extruder; and d) downstream ancillary equipment for cooling, cutting and/or collecting the finished product. In another embodiment of the present disclosure the processing time is in the range of 0.1-5 min.

[0082] In an another embodiment of the present disclosure there is provided a process for the preparation of a topical or transdermal film as described herein, wherein extruding the first mixture is done by twin-screw hot melt extrusion and shaping the extruding material is done by single screw hot melt extrusion process-flow comprising the following parts: a) an opening/hopper through which the at least one first active and the at least one water-soluble polymer layer enter the barrel or alternatively these may be continuously supplied in a controlled manner by one or more external feeder; b) a conveying section comprising the barrel and the screw(s) that transport, and where applicable, mix/homogenize the first mixture; c) orifice of the twin-screw extruder passes the homogenize mixture into an opening/hopper of single-screw hot melt extruder d) homogenize mixture enter the barrel or alternatively these may be continuously supplied in a controlled manner by the orifice of the twin-screw extruder; e) a conveying section of single-screw extruder comprising the barrel and the screw that transport homogenize mixture; f) an orifice/die for shaping the homogenize mixture as it leaves the extruder; and d) downstream ancillary equipment for cooling, cutting and/or collecting the finished product. In another embodiment of the present disclosure the processing time is in the range of 0.1 -5 min.

[0083] In an embodiment of the present disclosure there is provided a process for the preparation of a topical or transdermal film as described herein, wherein the finished product is cut to size. In another embodiment, the film composition will be further packaged, for example in a plastic or foil packet, in the form of a patch, or in other protective enclosures.

[0084] In an embodiment of the present disclosure, there is provided a system that delivers an effective amount of an active to the skin in a protected manner. In another embodiment of the present disclosure, the system comprises a composition comprising an effective amount of a first active agent incorporated into a water-soluble polymeric film and an additive composition capable of dissolving the water-soluble polymeric film. [0085] In an embodiment of the present disclosure, there is provided a system comprising a water- soluble polymer/ combination of polymer film, further comprising at least one water-soluble film- forming agent in which the active is incorporated. The water-soluble polymer such as maltodextrin also aid the property of actives with maintaining a moist environment beneficial for granulation tissue growth and epithelial proliferation for wound healing. Specifically, the water-soluble polymeric film does not contain any water or water-based ingredient, thereby avoiding the solubility and stability issues encountered when attempting to incorporate the actives within a film composition. Upon application of the water-soluble polymeric film to the skin and subsequent dissolution of the film, the active is effectively transferred to the skin in a substantially unaltered state to provide the desired pharmaceutical/cosmetic benefits.

[0086] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the water-soluble polymeric film should be inherently tacky or sticky/adhesive such that the film is capable of adhering to the skin upon application of the water- soluble polymeric film to the skin. Examples of the water-soluble film-forming agents that can produce a tacky, water- soluble polymeric film include but are not limited to collagen derivatives, cellulose derivatives, e.g., nitrocellulose, cellulose ether, carboxymethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose; pullulan, homo- and copolymers of vinyl pyrrolidone, e.g., PVP or PVP/PVA copolymers; homo- or copolymers of vinyl alcohol, such as polyvinyl alcohol, homo- or copolymers of acrylic and/or methacrylic acids, and salts and esters thereof, starches and derivatives thereof, or gums such as xanthan gum, gum arabica, guar gum, carob bean gum, cellulose gum, alginates, vegetable proteins, shellac, crotonic acid polymers, adipic acid polymers or carageenans, and mixtures thereof. In general, methods of making films from these water-soluble film-forming agents is well known in the art. It should be noted that more than one water-soluble polymeric film-forming agent may be used in combination to form a first layer in which the active is incorporated. Following water-soluble polymers were used for producing biofilm/bio cubes films with flexibility using tween screw hot melt extrusion: maltodextrin, hydroxypropyl methyl cellulose (HPMC-low viscosity), polyvinyl pyrrolidone (PVP K30 and PVP K12) and hydroxypropyl cellulose (HPC-low viscosity).

[0087] In an embodiment of the present disclosure there provided a wound healing biofilm, the composition comprises at least two layers of polymeric films. Preferably, a second water-soluble polymeric film is also used to provide physical stability to the final composition, thereby providing more lubrication and spreadability for the adhesive water-soluble polymeric film layer incorporating the first active. Such a second film should be used in such amounts so as not to interfere with the dissolvability of the composition on the skin. In an embodiment of the present disclosure, the second water-soluble polymeric film be different from the first water soluble polymeric film containing the at least one first active, and optionally the at least one second active, so that two discrete layers may be maintained.

[0088] Examples of useful water-soluble film- forming agents for this purpose, include, but are not limited to, polyethylene, high molecular weight polyethylene glycols (PEGs), hydrophilic siloxysilicates, hydrophilic silicone polyacrylates and combinations thereof. It should be noted that more than one water-soluble film-forming agent may be used in combination to form the second layer of water-soluble polymeric film, with the limitation that each of the agents of the second layer must be different from the water-soluble film-forming agent or agents of the first layer to maintain the two distinct layers. In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the water-soluble film-forming polymer/ combination of polymer of the first adhesive film layer is used in an amount of 30% to 80% by weight of the film composition preferably from 35% to 75%, and most preferably from 40% to 70%. In yet another embodiment for wound healing, the water-soluble film-forming agent of the second film layer is present in an amount of from 2% to 50% by weight of the wet composition, preferably from 4% to 40%, and most preferably from 6% to 30%.

[0089] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the film/ bio cube incorporating the active is made with a tween screw hot melt extrusion technology. Various drugs/medicaments/herbal actives/nutraceuticals/ cosmetics can be added to the product formula and can be prepared as follows: Mixing all of the powdered ingredients in one container (except surface active agent and plasticizer), adding glycerol, surface active agent and plasticizer and then processing the mixture through twin-screw hot melt extrusion. A uniform product can be obtained with desired attributes of film thickness and film width by optimization of process, formulation and equipment's parameters (chilled roller unit for stretching the films). Optionally other pharmaceutical acceptable excipients can also be added.

[0090] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the film comprises two layers for wound healing, the second layer of water-soluble polymeric film is adjacently adhered to a side opposite the active in the first water- soluble polymeric film by methods known to those skilled in the art, such that the second polymeric film does not interfere with the active. The second layer of water-soluble polymeric film is adhered by methods to those skilled in the art for creating polymeric layers, such as by roller laminating the second layer of water-soluble polymeric film upon the first layer of water-soluble polymeric film so that the second layer is adjacently adhered to the first layer, thereby creating two distinct layers. The second layer of water-soluble polymeric film may be roller laminated onto the first layer of water-soluble polymeric film by methods known in the art. In an embodiment, the water soluble polymeric film is composed of maltodextrin and HPC.

[0091] In an embodiment of the present disclosure, there is provided a topical or transdermal film as described herein, wherein the first water soluble polymeric layer comprises a combination of water soluble polymer maltodextrin, hydroxy propyl cellulose EF (HPC), and PVA, and wherein maltodextrin to HPC has a weight ratio in a range of 0.5: 1 to 7.5: 1. In another embodiment of the present disclosure, maltodextrin to HPC has a weight ratio in a range of 0.7: 1 to 7: 1.

[0092] In an embodiment of the present disclosure, there is provided a topical or transdermal film as described herein, wherein the first water soluble polymeric layer comprises a combination of water soluble polymer maltodextrin, hydroxy propyl cellulose EF (HPC), and PVA, and wherein the plasticizer is sorbitol, and wherein maltodextrin to HPC to sorbitol has a weight ratio in a range of 7-8: 1.25-15:0.4-4. In another embodiment of the present disclosure, maltodextrin to HPC to sorbitol has a weight ratio in a range of 7-7.5: 1.5-10:0.4-4.

[0093] The foregoing paragraphs describe the basic elements of the composition comprising a first active incorporated in to a water-soluble polymeric film. However, it may be desirable to incorporate other components into the film. In an embodiment of the present disclosure there is described a topical or transdermal film as described herein, wherein the film may further comprise a plasticizer incorporated therein to provide additional lubrication and spread for the water-soluble film-forming polymer. The plasticizer may be any material which does not interfere with the active, as would be known to those skilled in the art. If a plasticizer is used, the active or actives incorporated directly into the plasticizer and water-soluble film forming polymer using the methods described hereinabove. A nonlimiting list of exemplary materials which may act as plasticizers for the film forming polymers of the present disclosure includes sorbitol, glycerine, propylene glycol, diisobutyl adipate, acetyl tri-n-butyl titrate, di(2-ethyl hexyl) azelate, 2-ethyl hexyl diphenyl phosphate, diisoctyl isophthalate, isooctyl benzyl phthalate, butyl stearate, tri-2- ethyl hexyl trimellitate, N-octyl neopentanoate, diisostearyl malate, colloidal fumed silica (such as Cab-O-Sil®) and most perfume materials. In another embodiment of the present disclosure the plasticizer is a polyol such as glycerol, because of its known properties of providing plasticizing effects at minimal concentrations. The plasticizer, if used, is present in an amount from 2% to 15%, of the film composition.

[0094] Those skilled in the art will readily recognize that the foregoing components represent the preferred elements of the inventive film, but that other optional elements that constitute the cosmetic/therapeutic effect may be included. These optional elements are selected so as not to disturb and, in some cases, will preferably enhance the stability of the actives. Such optional components include but are not limited to, stabilizers, preservatives, surfactants, emulsifiers, dyes, anti-caking agents, absorption promoters or penetration enhancers, adherent, lubricant, and a second active.

[0095] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the film may further comprise a wetting solution such as simple tap water. Since the actives are relatively unstable when exposed to factors such as water or air, it is recommended that such actives be sheltered from such factors until the actives are transferred into the skin. However, in order to function on the skin, the water-soluble polymeric film is preferably wetted with an additive composition using a wetting solution. The wetting solution is used to wet the water-soluble polymeric film so that when the biofilm contacts with the skin, it is can adhere to the skin, while ensuring that the active is maintained, as part of the film, in a relatively stable state until the actual moment of application to the user's skin.

[0096] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the film may further comprise a number of additives and actives as long as such additives and actives are not of a nature or used in an amount to interfere with the aqueous nature of the additive composition, including, but not limited to such ingredient classes as described in The CTFA Cosmetic Ingredient Handbook, Tenth Edition (2004), including abrasives, absorbents, aesthetic components such as fragrances, pigments, colorings/colorants, essential oils, skin sensates, astringents, etc., anti-acne agents, anti-caking agents, antifoaming agents, antimicrobial, antioxidants, binders, biological additives, buffering agents, bulking agents, chelating agents, chemical additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, drug astringents, external analgesics, film formers or materials, e.g., polymers, for aiding the film-forming properties and substantivity of the composition, opacifying agents, pH adjusters, propellants, reducing agents, sequestrants, skin bleaching and lightening agents, skin- conditioning agents (e.g., moisturizers, emollients or humectants), skin soothing and/or healing agents, skin treating agents, thickeners, and vitamins and derivatives thereof. Although categorized by benefit, it should be noted that the actives useful herein can in some instances provide more than one benefit or operate via more than one mode of action.

[0097] The penetration enhancers or absorption promoters include, but not limited to, a- hydroxyacids, fatty acid esters and amides thereof, fatty alcohols, fatty acids and esters of glycerol in particular 2-(2-ethoxyethoxy)-ethanol, glycerolmonolaurate, propylene glycol, polyethylene glycols, polyglycosylic glycerides, unsaturated polyglycols, saturated polyglycerides, decylmethylsulfoxide, pyrrolidones, salicyilic acid, lactic acid, isopropyl myristate, dimethylformamide, dimethylacetamide, sodium dodecylsulfate, phospholipids, mixtures of oleic acid and 2-(2-ethoxyethoxy)-ethanol, enzymatic compounds, such as proteolytic enzymes, fatty acids including capric, lauric, myristic, palmitic, stearic, arachidic, behenic, lignoceric, myristoleic, palmitoleic, petroselinic, oleic, linoleic and linolenic acids.

[0098] Other known absorption promoters for nail drug delivery work by virtue of hydrolysis, keratolysis, denaturation or other equivalent mechanism which destroy the nail or the membrane. By way of example of absorption promoters that work in this manner, mention may be made of urea, amino acids including sulfydryl groups, alkylsulfoxides, and any equivalent compound which works by destroying or denaturing the nail and/or the membrane thereby enabling the pharmaceutical compound to penetrate the deeper layers of the membrane.

[0099] In an embodiment of the present disclosure, the absorption promoters are dissolved uniformly in the polymeric matrix layer. The quantity of each absorption promoter is from 0.1 to 30% by weight of the adhesive matrix layer, more preferably from 1 to 20% by weight and even more preferably from 2 to 10% by weight. More specifically, when the absorption promoter is DMSO, it is particularly preferred that the DMSO represent 2 to 6% by weight of the polymeric matrix.

[00100] Therefore, classifications herein are made for the sake of convenience and are not intended to limit the active to that particular application or applications listed. More specific examples of useful additional components in the additive composition include retinoids such as retinol, and esters, acids, and aldehydes thereof; ascorbic acid, and esters and metal salts thereof, tocopherol and esters and amide derivatives thereof; shark cartilage; milk proteins; alpha- or beta- hydroxy acids; DHEA and derivatives thereof; topical cardiovascular agents; clotrimazole, ketoconazole, miconozole, griseofulvin, hydroxyzine, diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine, monobenzone, erythromycin, tetracycline, clindamycin, meclocyline, hydroquinone, minocycline, naproxen, ibuprofen, theophylline, cromolyn, albuterol, hydrocortisone, hydrocortisone 21-acetate, hydrocortisone 17-valerate, hydrocortisone 17- butyrate, betamethasone valerate, betamethasone diproprionate, triaminolone acetonide, fluocinonide, clobetasol, proprionate, benzoyl peroxide, crotamiton, propranol, promethazine, and mixtures thereof. In another embodiment of the present disclosure, the formulations of the system are skin care patches used as a whitening product, incorporating actives such as undecylenoyl phenylalanine.

[00101] It should be noted that the ingredients in the additive composition may overlap those identified as actives in the water-soluble film forming polymer. However, the actives in the additive composition are used in the manner commonly used in cosmetic formulations and not to provide the surprisingly effective cosmetic benefit provided by delivering the first active in a relatively better protected state, as is found in the present inventive system.

[00102] In an embodiment of the present disclosure there is provided a topical or transdermal film as described herein, wherein the film may be applied to the skin, and thereafter adhere the film by application of simple tap water. In one embodiment, the package may be adapted to further stabilize the components by reducing exposure to environmental factors, i.e., it may be airtight or darkened to avoid exposure to light. The elements provided in the package may also be presented in different forms. For example, the film may be provided in a convenient dispenser, or may be individually packaged in plastic, foil, paper, cellophane, or glassine packets or envelopes in the form of a patch.

EXAMPLES

[00103] The disclosure will now be illustrated with working examples, which is intended to illustrate the working of disclosure and not intended to take restrictively to imply any limitations on the scope of the present disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice of the disclosed methods and compositions, the exemplary methods, devices and materials are described herein. It is to be understood that this disclosure is not limited to particular methods, and experimental conditions described, as such methods and conditions may vary.

[00104] The present disclosure aims at providing a transdermal or topical film that is easy to fabricate and modify based on the end-use. The films comprising at least one water-soluble polymeric layer and at least one first active. Furthermore, the HME-based fabrication allows rapid production of the films.

[00105] A nonlimiting list of possible first actives and corresponding benefits are provided in Table 1. In the case of inclusion of more than one first active into the present disclosure, the active(s) will be incorporated in an amount sufficient to deliver the known effective dosage of each particular first active.

Table 1

Zinc oxide Mild astringent and antiseptic

Diclofenac sodium Analgesic/anti-inflammatory.

[00106] The following examples further illustrate the invention, but the invention is not limited thereto. In the user's hands, the patch is applied to skin, where it is re-dissolved by means described hereinbelow. Examples 1 - 15 as provided below provide examples of formulations bearing various actives, expressed as percent weight/weight of the composition. Each of these topical or transdermal film forming formulations are prepared by a hot melt extrusion process. The process of the present disclosure is a versatile process allowing the preparation of a variety of topical or transdermal film compositions for various functions such as wound healing and personal care as exemplified in Examples 1- 15. In brief, the process followed for preparing the Examples as listed below comprising at least one first active and at least one first water-soluble polymer, is: (1) contacting the at least one first active and the at least one water-soluble polymeric later to obtain a first mixture was carried out in a kneading zone at a temperature in the range of 45-115 °C; and (2) extruding the first mixture was done by twin-screw hot melt extrusion and shaping the extruding material was done by single screw hot melt extrusion process-flow comprising the following parts: a) an opening/hopper through which the at least one first active and the at least one water-soluble polymer layer enter the barrel or alternatively these may be continuously supplied in a controlled manner by one or more external feeder; b) a conveying section comprising the barrel and the screw(s) that transport, and where applicable, mix/homogenize the first mixture; c) orifice of the twin-screw extruder passes the homogenize mixture into an opening/hopper of single-screw hot melt extruder d) homogenize mixture enter the barrel or alternatively these may be continuously supplied in a controlled manner by the orifice of the twin-screw extruder; e) a conveying section of single-screw extruder comprising the barrel and the screw that transport homogenize mixture; f) an orifice/die for shaping the homogenize mixture as it leaves the extruder; and d) downstream ancillary equipment for cooling, cutting and/or collecting the finished product. The thickness of all the Examples of the film is in a range of 0.02-5mm.

[00107]

[00108] Example 1: Water soluble antiaging biofilms with actives

Hydroxy propyl cellulose EF 10.0

Sodium alginate 2

Sodium lauryl sulphate 0.3

Sorbitol 14

Menthol 0.5

Citric acid 0.8

Cocoa powder/ chocolate 20

Diethylene glycol monoethyl ether 5

PVA 2

[00109] Example 2: Water soluble first layer biofilm (hydrophilic) for with actives

Ingredients (% w/w)

Maltodextrin 40.48

Hydroxy propyl cellulose EF 22.72

Sodium alginate 7

Sodium lauryl sulphate 0.3

Sorbitol 14

Menthol 0.5

Chitosan 2

Glucominan 1

Povidone iodine 10

PVA 2

[00110] Example 3: Water soluble second layer film for wound healing

Ingredients (% w/w)

Stelliester ester 15 SE 50

EVA 50

Example 4: Chitosan based matrix film for wound healing

Ingredients (% w/w)

Maltodextrin 21.95

Hydroxy propyl cellulose EF 41.05

Sodium alginate 2

Sorbitol 14

Chitosan 2 Sucroesters 10

Example 5: Antiwrinkle film for personnel care with actives

Example 7: Skin Whiting film for personnel care with actives

Diethylene glycol monoethyl ether 5

colloidal silicon dioxide 2

PVA 2

[00115] Example 8: Topical antioxidant film containing green tea powder/extract

[00116]

[00117] Example 10: Topical nail drug delivery film for treatment of onychomycosis

Menthol 1

Na Benzoate 0.8

colloidal silicon dioxide 2

Microcrystalline cellulose 1.2

DMSO 3

Sodium alginate 3

PVA 2

[00118] Example 11: Topical drug delivery film for tooth sensitivity treatment

[00119]

[00120] Example 13: Topical film for skin pigmentation/dark circle

[00121]

[00122] Example 15: Diclofenac sodium topical film for pain relief

Talc 2

colloidal silicon dioxide 2

Diethylene glycol monoethyl ether 5

PVA 2

Example 16: Physico-spectral characterization

[00123] To obtain satisfactory flexibility and endurance, a two-polymer film was developed. Following water-soluble polymers were used for producing biofilm/bio cubes films with flexibility using tween screw hot melt extrusion: maltodextrin, hydroxypropyl methyl cellulose (HPMC-low viscosity), polyvinyl pyrrolidone (PVP K30) and hydroxypropyl cellulose (HPC-low viscosity). The details of the optimization ratio are given in Table 2 as follows:

Table 2

[00124] Based on the observations made in the Table 2, the polymer combination for preparation of biofilms/bio cubes was selected for twin-screw hot melt extrusion. The Maltodextrin to HPC (low viscosity) in the weight ratio range of 0.5: 1 to 7.5: 1 was used as final polymer combination for producing adhesive biofilms of various actives and cosmetics at high dose loadings. Alternatively, a ratio of 58:29 was found to be effective for low dose loading. In an embodiment, the ratio of maltodextrin to HPC is 7: 1.25. In another embodiment, the ratio of maltodextrin to HPC is 7: 13. In yet another embodiment, the ratio of maltodextrin to HPC is 7:2.02. The films made with twin screw extrusion were evaluated for parameters like thickness, folding endurance, tensile strength, % elongation, surface pH, contact angle, drug distribution in the film, film thickness uniformity from the die, film flexibility and topographical studies to observe the surface of the film in detail. It should be noted that when maltodextrin and HPC weight ratio is considered the working range is 0.5:7.5: 1, in a case when maltodextrin, HPC, and sorbitol are considered, 7: 1 : 1-3 is non-working, whereas a range of 7: 1.25-14:0.4-4 is working with respect to the type of film formed. Thus, a combined weight ratio of maltodextrin, HPC, and sorbitol is crucial for obtaining films with desired qualities.

Example 17: Selection of plasticizer

[00125] The flow of polymer will be improved with the use of plasticizer that enhances the strength of the polymer. Plasticizers such as glycerol, propylene glycol etc are generally used. The Plasticizer employed should impart the permanent flexibility to the film which depends on the volatility of the plasticizer and the type of interaction with the polymer. Maltodextrin and PVP were used in combination as the film formers and the amount of plasticizer was optimized. Three plasticizers propylene glycol (PG), glycerine and sorbitol were screened.

Table 3

Table 5 Maltodextrin : HPC: Sorbitol

Ratio Physical characteristics

7:1:1 The films formed were sticky and lost

7:1:2 flexibility

7:1:3 Sticky films were formed

7-8:1.25-14:0.4-4 Films with desired flexibility and thickness were formed

[00126] From the results enlisted in Tables 3-5, it is evident that the optimization of plasticizer revealed that both glycerine and PG performed well. Both the plasticizers provided a flexible film, whereas the films obtained with sorbitol were found to be sticky and undesirable. However, sorbitol was found to provide acceptable result in combination with an anti-sticking agent. The ratio of the Maltodextrin: HPC: Sorbitol is in a ratio range of 7-8: 1.25-14:0.55-5. In a preferred embodiment, the ratio of the Maltodextrin: HPC: Sorbitol is 7: 1.25:2.25. In another embodiment, the ratio of the Maltodextrin: HPC: Sorbitol is 7: 1.25:0.4. In another embodiment of the present disclosure, the plasticizer employed was glycerine as it performed a dual function of being a sweetening agent.

Example 18: Franz Diffusion Cell Study for Povidone Iodine wound healing film

[00127] The Franz Cell apparatus consists of two chambers separated by a membrane of animal or human skin. The test product was applied to the membrane via the top chamber. The bottom chamber contains fluid from which samples are taken at regular intervals for analysis to determine the amount of active that has permeated the membrane at set time points. Povidone iodine was used as an active for representative of all the actives in the film which supposed to penetrate the skin. Povidone iodine was chosen due to its color forming property and easy UV characterization.

[00128] For this purpose, 1.2 grams of povidone iodine wound healing film sample was applied to the cellulose membrane mounted on the Franz diffusion cell and 20mL of simulated fluid was introduced to the lower cell. A water jacket of the permeation cell maintained the system at 32°C. The rate of increase of iodine concentration in the receptor compartment was assumed to be in proportion to the iodine concentration in the donor compartment. The permeability of iodine through cellulose membrane with a thickness of 0.1mm, pore size 0.45micron and permeation cell commercially available was measured at 32°C. The percent of free-iodine concentration released from film was estimated. The experimental conditions while performing the study are herewith indicated below in Table 6.

Table 6

From Figure 1 , it can be observed that the concentration of iodine in the receptor compartment has not increased linearly over time. Fig. 2 shows that prepared film formulation retained on the membrane in receptor cell during the diffusion study and Figure 3 represent no significant color change due to povidone iodine in donor cell during diffusion study. From a combined reading of Figure 1, 2 and 3, it can be inferred that the prepared povidone iodine wound healing film retarded the diffusion of povidone iodine which prevents iodine toxicity in the body.

Diffusion study on two different membranes: Povidone iodine was used as an active for representative of all the actives in the film which supposed to penetrate the skin. Povidone iodine was used due to its colour forming property and easy UV characterization. Prepared topical film formulation gradually diffuse through both the membrane PVDF and Cellulose nitrate with time. The percentage release of iodine on use of two different membranes was studied for 4 hours, and the results are presented in Table 7.

Table 7

From Table 7, it can be understood that the prepared topical film formulation gradually diffused through both the membrane PVDF and Cellulose nitrate with time. At 4hr time point release of iodine was measured as more than 85% after diffusion through both the membrane. The results reveal that povidone iodine successfully diffused through both the membrane equivalent to skin pore size from prepared topical film for skin penetration.

Example 19: In vitro antimicrobial agar disc diffusion efficacy method

[00129] Agar plates were inoculated with a standardized inoculum of the test microorganism i.e. Staphylococcus aureus. Then, filter paper discs (about 6 mm in diameter), containing the test compound at a desired concentration (povidone iodine, 10%), were placed on the agar surface. The petri dishes were incubated under suitable conditions, povidone iodine (antimicrobial agent) diffused into the agar and inhibits the growth of the microorganism. Further, the diameters of inhibition growth zones were measured, and the results are depicted in Figure 4 and 5. Test were done by Bangalore Analytical Research Centre (P.) Ltd. As shown in Figure 5 the inhibition growth zone was observed as 2.3 cm for the povidone iodine, and the results were found to be comparable to that of the control (Betadine PI ointment), wherein the inhibition growth zone was 2.5cm. The results suggest that the povidone iodine film shows antimicrobial efficacy. Example 20: Evaluation of the topical or transdermal film forming actives

[00130] The film forming actives, as described in Example 1-15, were further subjected to

Franz diffusion cell study to determine the percentage release of actives through the cell membrane (modelling real skin) to screen the effect of the actives on the skin. All the tests were conducted by Bangalore Analytical Research Centre (P.) Ltd. The results show that a) the percent purity of povidone iodine in wound healing topical film was found to be 108.0%; b) the percent purity of hydrogen peroxide (30%) in tooth whitening film was found to be 102.77%; c) the percent purity of Potassium nitrate in tooth sensitivity topical film was found to be 90.6%; d) the percent purity of adapalene in anti-acne topical film was found to be 116%; e) the percent purity of ciclopirox olamine in nail drug delivery topical film was found to be 116.5%.

Example 20: Dissolution study of topical film formulation prepared for skin penetration

[00131] Dissolution study were done at Bangalore Analytical Research Centre (P.) Ltd.

Topical film for tooth sensitivity were used as reference sample for dissolution study. Results are shown in Table 8.

Table 8 Result in

Test Sample name Method

percentage

Sample 1 114.7%

Colorimetric method

Dissolution test at 5 Sample 2 119.5%

(wavelength

min Sample 3 112.0%

measured at 540nm)

Sample 4 115.8%

To represent the dissolution of topical films, tooth sensitivity topical film containing potassium nitrate act as an active was chosen for study. Table 8 reveals that whole active released within 5 min during dissolution in simulated buffer. All the prepared samples released more than 100% active. Release was greater than 100% because of average weight of the film was ±5mg than actual weight of the film i.e. lOOmg. The results conclude that the prepared topical film platform released more than 100% active in 5minutes.

Example 21: Measurement of physical parameters:

[00132] The thickness of the formulated biofilms was measured using Mitutoyo absolute digital vernier calliper. This is essential to ascertain uniformity in the thickness of the film. The thickness of the film sample is measured at five locations (centre and four corners), and the mean thickness. The values reported below are mean of 5 repeated values. Also determined are the folding endurance, tensile strength, percentage elongation, surface pH and contact angle. These have been enlisted in Table 9 below. Table 9 below refers to the properties of hair removal film comprising calcium thioglycolate as an active.

Table 9

Contact angle: [00133] Contact angle measurement predicts the wetting behavior, disintegration time, and dissolution of oral film. These measurements are performed with help of goniometer and the measurements were done at room temperature. The water used to determine contact angle should be double distilled water. A drop of double distilled water is placed on the surface of dry film. Images of water droplet are recorded within 10 s of deposition by means of digital camera. Digital pictures can be analyzed by image J 1.28v software (NIH, USA) for angle determination (Figure 6). Contact angle of film represent the all first layer water soluble topical film. It will change for matrix and second layer.

[00134] Generally, if the water contact angle is smaller than 90°, the solid surface is considered hydrophilic and if the water contact angle is larger than 90°, the solid surface is considered hydrophobic. Most polymers exhibit hydrophobic surfaces. However, the films described in the present disclosure were hydrophilic with a contact angle of 20°.

Tensile Strength:

[00135] The mechanical testing of the films using American Society for Testing and

Materials (ASTM) standards protocol (ASTM D882). Tensile testing determines the amount of stress each material can sustain prior to failure as well as the amount of elongation at the time of failure. Each specimen measured 80 mm (length) x 5 mm (width) x 2 mm (thickness). The tests were conducted using Brookfield Engineering CT3 texture analyzer with tensile jig and with a crosshead speed of 1 mm/s. The films were placed in the tensile jig holder, parallel to the direction of analysis. The analysis was repeated in 10 samples each and the average values are reported (Figure 7).

[00136] Tensile strength is a property which is characteristic for each material/ingredient.

From Figure 2, it can be observed that tensile strength for twin-screw extruded topical antioxidant film containing cocoa/ chocolate powder with average tensile strength of 532g (5.2 IN), the films developed using HME are durable enough to sustain the physical or environmental shocks.

FE SEM Micrograph study:

[00137] The cross-sectional area and surface morphology of topical film was observed using

FE-SEM study (Figure 8). It was observed that surface of the film had minimal defects and the film was smooth and shiny.

Topographical study using AFM: [00138] The uniform distribution of the actives was observed by using topographical AFM analysis (Figure 9). The AFM analysis revealed a smooth and coherent film. It was observed that the distribution of active was uniform in the antioxidant film.

[00139] Although the subject matter has been described with reference to specific embodiments, this description is not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternate embodiments of the subject matter, will become apparent to persons skilled in the art upon reference to the description of the subject matter. It is therefore contemplated that such modifications can be made without departing from the present subject matter as defined.

Advantages of the present disclosure

[00140] The present disclosure reveals a topical or transdermal film comprising: a) a composition comprising at least one first active; and b) at least one water-soluble polymeric layer, wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one water soluble polymeric layer has a weight that is at least 0.5 times the weight of at least one first active but not more than 80,000 times the weight of the at least one first active. The topical films of the present disclosure are capable of delivering a wide range of actives into the skin and possess excellent activity against burn healing, wound healing, skin lightening, and skin rejuvenation. Also, the topical or the transdermal films of the present disclosure can be prepared by a single step, thereby saving a substantial amount of time, cost, and energy. Further, the ease of preparation of the films make the whole process industrially scalable with less foot print. Overall, the results demonstrate that the films of the present disclosure can be used effectively for administration of actives through the skin, thereby making the entire process of administration less painful and convenient to the patient/the user.

Claims

I/We Claim:

1. A topical or transdermal film comprising:

a) a composition comprising at least one first active; and

b) at least one first water-soluble polymeric layer,

wherein the polymeric layer forms a polymer matrix and the at least one first active is dispersed throughout the polymer matrix, and the at least one first water soluble polymeric layer and the at least one first active has a weight ratio in a range of 0.5: 1 to 80,000: 1.

2. The topical or transdermal film as claimed in claim 1, optionally comprising a second water-soluble polymeric layer.

3. The topical or transdermal film as claimed in any one of the claims 1 and 2, wherein the composition further comprises at least one additive selected from a group consisting of fragrance, flavor, plasticizer, stabilizer, preservative, surfactant, emulsifier, anti-caking agent, permeation enhancer, lubricant, adherent, dye, and at least one second active.

4. The topical or transdermal film as claimed in any one of the claims 1 - 3, wherein the at least one first water-soluble polymeric layer comprises a water-soluble polymer selected from a group consisting of collagen derivatives, cellulose derivatives, pullulan, homo- and copolymers of vinyl pyrrolidone, homo- or copolymers of vinyl alcohol, starches and derivatives thereof, gums, alginates, vegetable proteins, shellac, crotonic acid polymers, adipic acid polymers or carageenans, and combinations thereof.

5. The topical or transdermal film as claimed in any one of the claims 1 - 4, wherein the at least one fist active is selected from a group consisting of wound healing agents, antiseptics, antioxidants, antiaging agents, whitening agents, UV -protective agents, skin conditioning agents, analgesic agents, bleaching agents, desensitizing agents, antifungal agents, anti-burn agents, and combinations thereof.

6. The topical or transdermal film as claimed in claim 2, wherein the second water-soluble polymeric layer comprises a water-soluble polymer selected from a group consisting of polyethylene glycol, hydrophilic siloxysilicates, hydrophilic silicone polyacrylates, and combinations thereof.

7. A topical or transdermal film as claimed in claim 1, comprising: a) at least one first active having weight percentage in a range of 0.001 - 60% with respect to the film; and

b) at least one first water-soluble polymeric layer having weight percentage in a range of 30 - 80% with respect to the film,

wherein the polymeric layer forms a polymer matrix and the at least first one active is dispersed throughout the polymer matrix.

8. The topical or transdermal film as claimed in claim 7, optionally comprising a second water-soluble polymeric layer having weight percentage in a range of 2 - 50% with respect to the film.

9. The topical or transdermal film as claimed in any one of the claims 7 and 8, wherein the composition further comprises at least one additive selected from a group consisting of: (a) fragrance having weight percentage in a range of 0-2% with respect to the film, and selected from a group consisting of floral fragrances, essential oils, spearmint, tea tree, juniper, aloe, cucumber, musk, and combinations thereof; (b) flavor having weight percentage in a range of 0-2% with respect to the film, and selected from a group consisting of menthol, vanilla, orange, butter scotch, pista, strawberry, aloe vera, amla, neem extract, cucumber, and combinations thereof; (c) plasticizer having weight percentage in a range of 2 - 20% with respect to the film, and selected from a group consisting of sorbitol, propylene glycol, glycerol, diisobutyl adipate, acetyl tri-n-butyl citrate, di(2-ethyl hexyl) azelate, 2-ethyl hexyl diphenyl phosphate, diisoctyl isophthalate, isooctyl benzyl phthalate, butyl stearate, tri-2-ethyl hexyl trimellitate, N-octyl neopentanoate, diisostearyl malate, and colloidal fumed silica; (d) stabilizer having weight percentage in a range of 0.001- 0.05% with respect to the film, and selected from a group consisting of natural gums, artificial gums, and combinations thereof; (e) preservative having weight percentage in a range of 0.001- 0.05% with respect to the film, and selected from a group consisting of vitamin C, vitamin E, butylated hydroxytoluene (BHT), butylated hydroxy anisole (BHA), benzoates, parabens, sorbate, citric acid, polyphosphates, ethylenediaminetetraacetic acid (EDTA), sodium chloride, lemon, neem oil, honey, propionates, nitrites, and combinations thereof ; (f) surfactant having weight percentage in a range of 0.01-1% with respect to the film, and selected from a group consisting of, sodium lauryl sulphates, and combinations thereof; (g) emulsifier having weight percentage in a range of 0.001-1% with respect to the film, and selected from a group consisting of emulsifying wax, polysorbate 80, tween 20, tween 80, and combinations thereof; (h) dye selected from a group consisting of xanthine, pyrazolone, indigoid, triphenyl methane, and combinations thereof; (i) at least one second active having weight percentage in a range of 10-80% with respect to the film, and selected from a group consisting of monosaccharides, disaccharides, polysaccharides, carbohydrates selected from a group consisting of lactose, dextrose, starch, mannitol, maltose, sucrose, and combinations thereof, and combinations thereof, (j) at least one anti- caking agent having a weight percentage of 0.5-10% with respect to the film, and selected from a group consisting of microcrystalline cellulose, sodium lauryl sulfate, silicon dioxide, polyoxyethylene alkylethers, benzethonium chloride, dibutyl tartrate, and combinations thereof, (k) at least one lubricant having a weight percentage of 0.5-10% with respect to the film, and selected from a group consisting of talc, magnesium silicate, stearic acid, , sucrose esters, and combinations thereof (1) at least one adherent having a weight percentage of 0.5-52% with respect to the film, and selected from a group consisting of carboxymethyl cellulose sodium (sodium CMC)/sodium alginate, agar, xantham gum, carrageenan, locust bean gum, guar gum, gum tragacanth, and combinations thereof, and (m) at least one penetration enhancer having a weight percentage in a range of 0.1 - 30% in the film, and selected from a group consisting of dimethyl sulfoxide (DMSO), a- hydroxyacids, fatty acid esters and amides thereof, fatty alcohols, fatty acids and esters of glycerol, saturated polyglycerides, decylmethylsulfoxide, pyrrolidones, salicyilic acid, lactic acid, isopropyl myristate, dimethylformamide, dimethylacetamide, sodium dodecylsulfate, phospholipids, mixtures of oleic acid and 2-(2-ethoxyethoxy)-ethanol, fatty acids, enzymes, urea, alkylsulfoxides, and combinations thereof.

10. The topical or transdermal film as claimed in any one of the claims 1 - 9, wherein the film has: (a) thickness in a range of 0.02 - 5 mm for the film; (b) folding endurance of topical film in a range of 1-2; (c) tensile strength in a range of 1-lON/m²; (d) percentage elongation in a range of 10-60%; (e) surface pH in a range of 5 - 6.5; and (f) contact angle in a range of 0-90 degree.

11. The topical or transdermal film as claimed in any one of the claims 1 - 10, wherein the film is transformed into a product selected from a group consisting of topical or transdermal patch, mask, and biocube.

12. The topical or transdermal film as claimed in claim 11, wherein the film is transformed into a patch, and wherein the patch on application onto skin of a subject, followed by dissolution of the at least one water-soluble polymeric layer, leads to the transfer of the at least one first active to skin.

13. The topical or transdermal film as claimed in any one of the claims 1 - 11, for use as a topical or transdermal product for burn healing, wound healing, skin lightening, and skin rejuvenation.

14. A process for the preparation of the topical or transdermal film as claimed in claim 1, said process comprising:

a. obtaining a composition comprising at least one first active;

b. obtaining at least one first water soluble polymeric layer;

c. contacting the at least one first active with the at least one first water soluble polymeric layer to obtain the first mixture; and

d. extruding the first mixture to obtain the topical or transdermal film.

15. The process for preparation of the film as claimed in claim 14, wherein contacting the at least one first active with the at least one first water soluble polymeric layer is carried out a temperature in a range of 45-115 °C.

16. The process for preparation of the film as claimed in claim 14, wherein extruding the first mixture is carried out through a twin screw hot melt extrusion method.