AU2021106678A4 - A method of preparation of Triamcinolone Acetonide encapsulated nanostructured lipid carriers for psoriasis treatment. - Google Patents
A method of preparation of Triamcinolone Acetonide encapsulated nanostructured lipid carriers for psoriasis treatment. Download PDFInfo
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- AU2021106678A4 AU2021106678A4 AU2021106678A AU2021106678A AU2021106678A4 AU 2021106678 A4 AU2021106678 A4 AU 2021106678A4 AU 2021106678 A AU2021106678 A AU 2021106678A AU 2021106678 A AU2021106678 A AU 2021106678A AU 2021106678 A4 AU2021106678 A4 AU 2021106678A4
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- lipid carriers
- nanostructured lipid
- triamcinolone acetonide
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Classifications
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- A—HUMAN NECESSITIES
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- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5123—Organic compounds, e.g. fats, sugars
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Abstract
:
A method of preparation of Triamcinolone Acetonide encapsulated
nanostructured lipid carriers for psoriasis treatment
This invention describes a Triamcinolone acetonide (TA) enriched Nanostructured
Lipid Carriers (NLC)s based topical formulation for psoriasis, where docosahexaenoic
acid (DHA) has been employed to play a dual role as formulation ingredient of
Nanostructured Lipid Carriers (NLC) as well as to exhibit anti-inflammatory activity.
For effective transepidermal delivery, the synergistic potential of the omega 3 fatty
acid-basedTriamcinolone acetonide (TA)-loaded Nanostructured Lipid Carriers
(NLC) system is used. The prepared drug is loaded into Nanostructured Lipid Carriers
(NLC)s to help viable infiltration of the medications across the skin for optimum
therapeutic benefits. The Nanostructured Lipid Carriers (NLC)s is further integrated
into a hydrogel matrix to get a longer contact time & for easy topical application,
proper spreading, and absorption on the skin.
Signatory
Manju Rawat Singh
Deependra Singh
K.K.Sahu
Madhulika Pradhan
Krishna Yadav
1
Description
TITLE A method of preparation of Triamcinolone Acetonide encapsulated nanostructured lipid carriers for psoriasis treatment
[0001] This invention relates to the pharmaceutical and medical sciences more particularly a method of synthesizing Nanostructured Lipid Carriers (NLC) encapsulated with Triamcinolone acetonide (TA) for treating proliferative skin diseases like psoriasis.
[0002] Here Triamcinolone acetonide (TA) enriched Nanostructured Lipid Carriers (NLC)s based topical formulation is developed for psoriasis, where docosahexaenoic acid (DHA) has been employed to play a dual role as formulation ingredient of Nanostructured Lipid Carriers (NLC) as well as to exhibit anti-inflammatory activity. For effective transepidermal delivery, the synergistic potential of the omega 3 fatty acid-basedTriamcinolone acetonide (TA)-loaded Nanostructured Lipid Carriers (NLC) system is used.
[0003] Psoriasis is a chronic skin disorder that is proliferative and widespread throughout the world, afflicting millions of humans and even domesticated animals having similar proliferative integument problems. The skin disorder is characterized by recurrent, elevated red lesions, plaques or rarely pustules on the skin. These plaques are the results of an excessively rapid growth and shedding of epidermal (skin) cells. No one knows what causes this abnormal cell proliferation. Its severity and course vary greatly from case to case, and also in the individual afflicted with the disease. Recurrences are almost the rule with intervals varying from one month to many years. One person may go through life with a single patch on the elbow, knee or scalp, while another will have repeated attacks of a generalized eruption of widespread chronic lesions lasting for years without remission. As discouraging as it may be, medical science and literature are replete with indications that patients exhibiting such lesions are destined for life to be "psoriatic." With all of the advances in medical science, no one knows what causes this abnormal cell proliferation. With some of it, it is felt that some type of biochemical stimulus triggers this abnormal cell growth. It is still unknown whether the origin of this biochemical malfunction resides in the skin, in the immune system, in the white blood cells, or is possibly psycho-neural. It is known that certain environmental factors can "trigger" the initial appearance or worsening of psoriasis. Conversely, the symptoms can spontaneously clear for reasons scientists do not understand. Treatment of psoriasis is aimed at clearing the lesions for as long as possible. This is what is meant by the term "remission" or "clearance." In any event, medical science has fairly well agreed that psoriasis is a heritable disease in which the specific defect seems to be unknown.
[0004] For years there have been many attempts to treat the disease, and several topical and systemic treatments for psoriasis which inhibit cell division have been with limited success in clearing the skin for short periods. Yet, the reason why these treatments work is not yet clearly understood. Treatments that have been suggested in the art appear to be symptomatic and palliative. Lesions may disappear spontaneously or as a result of the therapy, but recurrences are likely. There is a tendency for each remedy gradually to lose its effectiveness or develop dangerous accumulative toxicity. Rarely, however, is the disease cured, showing no evidence for years.
[0005] In the treatment of the disease, medical science has suggested low fat or low protein diets. Drugs such as systemic corticosteroids and ACTH are effective but limited to patients who are in great distress and do not respond to other measures. Such drugs may produce dangerous side effects; and in some instances, once the drugs are discontinued, the eruption may show a marked exacerbation. Folic acid antagonists have been found to have some beneficial treatments but are a dangerous form of therapy. Although other drugs have been suggested, for the most part, the serious side effects associated therewith have not made them successful. Ionizing radiation therapy, e.g. Grenz-ray treatment, has provided only temporary benefit, but the danger(s) of addiction to such radiation-producing radiodermatitis and subsequent carcinoma is not worth continued treatment. Corticosteroid ointment in combination with polyethene film has had some success, but systemic effects may be caused by extensive use. Ointments are more beneficial than lotions. A typical ointment may contain anthralin or tar. A hydrophilic ointment containing salicylic acid and sulfur is also found to be beneficial, especially for scalp treatment. Here again, the side effects and the absorption within the human system of these chemicals must be guarded. Other treatments including sunlight baths or ultraviolet (UV) baths with the lesions painted with a solution of coal tar, anthralin or psoralens are helpful.
[0006] Ongoing studies in the art concern the use of vitamin D3 (1,25-dihydroxy vitamin D3). Etretin and Etretinate are new generation retinoids presently being studies for treating psoriasis, but again, the side effects must be carefully monitored. Other ongoing studies include the use of the drug cyclosporine, (a non-steroidal, anti-inflammatory drug), fish oil, hypothermia, and anti-yeast agents. There is no known cause, although many theories are advanced. They have no known cure, although many similar temporary remedies are known. All of these conditions are known to worsen with stress. Finally, there seems to be a hereditary basis or tendency for the development of each of these skin diseases, although this is not a strict finding
[0007] To resolve the above problem Triamcinolone acetonide (TA)-loaded Nanostructured Lipid Carriers (NLC)s are developed and optimized empirically for effective transepidermal delivery. The prepared drug is loaded into Nanostructured Lipid Carriers (NLC)s to help viable infiltration of the medications across the skin for optimum therapeutic benefits. The Nanostructured Lipid Carriers (NLC)s is further integrated into a hydrogel matrix to get a longer contact time & for easy topical application, proper spreading, and absorption on the skin.
[0008] Psoriasis is a chronic inflammatory skin disease of unknown cause, characterized by the development of reddish patches of skin covered with silvery-white imbricated scales. The disease generally affects the extensor surfaces of the body, along with the back and scalp. It is believed that the disease is determined in part by a genetically dominant trait. Psoriasis is not passed from person to person but is probably genetically linked. Although psoriasis is incurable, it can be managed to varying degrees by applying one or more treatment schemes.
[0009] It has already been proposed wherein the application of emollients, vitamin D or derivatives thereof (calcipotriol), and cortisone is suggested by the specialist. Cortisone may also be injected in specific locations in which the disease is especially persistent. Another type of topical treatment utilizes retinoids which are related to vitamin A. Such may be applied locally alone or in combination with cortisone. Systemic treatments used for psoriasis are drugs that affect the whole body. For example, cyclosporine is used in cases of widespread psoriasis. This treatment is potentially harmful and must be monitored carefully.
[0010] The principal objective of the invention is the synthesis of Nanostructured Lipid Carriers (NLC) encapsulated with Triamcinolone acetonide (TA) for treating proliferative skin diseases like psoriasis.
[0011] Another objective of the invention is that docosahexaenoic acid (DHA) has been employed to play a dual role as formulation ingredient of Nanostructured Lipid Carriers (NLC) as well as to exhibit anti-inflammatory activity.
[0012] The further objective of the invention is that for effective transepidermal delivery, the synergistic potential of the omega 3 fatty acid-based Triamcinolone acetonide (TA)-loaded Nanostructured Lipid Carriers (NLC) system is used.
[0013] The further objective of the invention is that the Nanostructured Lipid Carriers (NLC)s is further integrated into a hydrogel matrix to get a longer contact time & for easy topical application, proper spreading, and absorption on the skin.
[0014] Psoriasis is a chronic disease of unclear pathogenesis, affecting skin and joints in -2% of the population in developed countries. The disease causes significant morbidity. Some of its main characteristics are inflamed, scaly and frequently disfiguring skin lesions and arthritis of the joints in hands and feet. Typically, in skin lesions, altered differentiation of epidermal keratinocytes accompanies keratinocyte hyperproliferation. Marked infiltrates of T-cells and neutrophils are characteristic of psoriatic skin and are directly involved in the inflammatory state of the affected tissue. In addition, a distinct increase in skin capillaries is a typical phenomenon in psoriasis. Psoriatic arthritis appears in 10-30% of patients. In addition, the disease causes psoriatic skin lesions which are very itchy and which can result in severe scratching and disfigurement. The various manifestations of the disease make it more than a dermatologic nuisance as it interferes with many daily activities of the afflicted. As a consequence, the disease also causes considerable psychological morbidity in many patients. Current therapy for psoriasis includes anti-inflammatory agents such as steroids, specific anti inflammatory cytokines and chemokines, and agents acting as anti autoimmune therapies. While several of these therapies provide relief, many have undesirable side effects and none provide a cure.
[0015] So here Triamcinolone acetonide (TA) enriched Nanostructured Lipid Carriers (NLC)s based topical formulation is developed for psoriasis, where docosahexaenoic acid (DHA) has been employed to play a dual role as formulation ingredient of Nanostructured Lipid Carriers (NLC) as well as to exhibit anti-inflammatory activity. For effective transepidermal delivery, the synergistic potential of the omega 3 fatty acid-basedTriamcinolone acetonide (TA)-loaded Nanostructured Lipid Carriers (NLC) system is used. The prepared drug is loaded into Nanostructured Lipid Carriers (NLC)s to help viable infiltration of the medications across the skin for optimum therapeutic benefits. The Nanostructured Lipid Carriers (NLC)s is further integrated into a hydrogel matrix to get a longer contact time & for easy topical application, proper spreading, and absorption on the skin.
[0016] While the present invention is described herein by way of example, using various embodiments and illustrative drawings, those skilled in the art will recognize that the invention is neither intended to be limited to the embodiment of drawing nor drawings described nor designed to represent the scale of the various components. Further, some components that may form a part of the invention may not be illustrated with specific figures, for ease of illustration, and such omissions do not limit the embodiment outlined in any way. The drawings and a detailed description of it are not intended to restrict the invention to the form disclosed, but on the contrary, the invention covers all modifications, equivalents, and alternatives falling within the spirit and scope of the present invention as defined by the appended claims. The headings are used for organizational purposes only and are not meant to limit the scope of the description or the claims. As used throughout this specification, the word "may" be used in a permissive sense (i.e., meaning having the potential to), rather than the mandatory sense (i.e., meaning, must).
[0017] Further, the words "an" or "a" means "at least one" and the word "plurality" means one or more unless otherwise mentioned. Furthermore, the terminology and phraseology used herein are solely used for descriptive purposes and should not be construed as limiting in scope. Language such as "including," "comprising," "having," "containing," or "involving," and variations thereof, is intended to be broad and encompass the subject matter listed thereafter, equivalents and any additional subject matter not recited, and is not supposed to exclude any other additives, components, integers, or steps. Likewise, the term "comprising" is considered synonymous with the terms "including" or "containing" for applicable legal purposes. Any discussion of documents acts, materials, devices, articles, and the like are included in the specification solely to provide a context for the present invention.
[0018] In this disclosure, whenever an element or a group of elements is preceded with the transitional phrase "comprising", it is also understood that it contemplates the same element or group of elements with transitional phrases "consisting essentially of, "consisting", "selected from the group comprising", "including", or "is" preceding the recitation of the element or group of elements and vice versa.
[0019] Before explaining at least one embodiment of the invention in detail, it is to be understood that the present invention is not limited in its application to the details outlined in the following description or exemplified by the examples. The invention is capable of other embodiments or of being practised or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for description and should not be regarded as limiting.
[0020] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Besides, the descriptions, materials, methods, and examples are illustrative only and not intended to be limiting. Methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention.
[0021] The present invention provides a method of synthesizing Nanostructured Lipid Carriers (NLC) encapsulated with Triamcinolone acetonide (TA) for treating proliferative skin diseases like psoriasis.
[0022] Triamcinolone acetonide (TA) is the most widely used, diverse therapeutically-efficient glucocorticosteroid in the therapy for psoriasis. This is an anti-inflammatory, vasoconstrictive, immunosuppressive, and anti proliferating drug in cutaneous diseases. Pharmacodynamically, the corticosteroids block phospholipase A2, a key regulatory factor for arachidonic acid, prostaglandin production, and leukotrienes that is one of the key routes for the pathogenesis of psoriasis
[0023] For the transdermal delivery conveyance of medications, Nanostructured Lipid Carriers (NLC)s has shown prominence. The Nanostructured Lipid Carriers (NLC) are enriched with cardinal highlights including better infiltration of medication and high capture of the drug. It is highly dispersible in a fluid medium, and efficient in controlling the release rate of captured moiety synchronized by solid and liquid lipid combination covering.
[0024] Here in the embodiment, Triamcinolone acetonide (TA) enriched Nanostructured Lipid Carriers (NLC)s based topical formulation for psoriasis, where docosahexaenoic acid (DHA) has been employed to play a dual role as formulation ingredient of Nanostructured Lipid Carriers (NLC) as well as to exhibit anti-inflammatory activity. The method uses an omega 3 fatty acid-based Triamcinolone acetonide (TA)-loaded Nanostructured Lipid Carriers (NLC) system for effective transepidermal delivery. The drug is loaded into Nanostructured Lipid Carriers (NLC)s to help viable infiltration of the medications across the skin for optimum therapeutic benefits.
[0025] For the preparation of Triamcinolone acetonide (TA) containing Nanostructured Lipid Carriers (NLC)s, the materials consisted of docosahexaenoic acid (DHA) and the dialysis membrane (D9652-OOFT), cetostearyl alcohol (CSA), Carbopol 934, Poloxamer 188, Triethanolamine, and Haematoxylin and Eosin (H&E) dye. The Lipoid S100, ultra-clean water.
[0026] Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s were produced utilizing a melt dispersion technique. The lipid phase was produced by melting the CSA and DHA in a water bath at 70°C, after which the appropriate amount of the Triamcinolone acetonide (TA) was dispersed into the molten lipid phase. An aqueous solution containing poloxamer 188 and lipoid S100, was developed by heating at 70°C and adding the ingredients. It took around 3 hours to produce an emulsion when the aqueous phase was progressively added to the liquid lipid mixture under the regulation of a high speed homogenizer (Ultra turrax basic IKA 18) operating at 10000 revolutions per minute, at 70°C. Then, the emulsion was immediately chilled to approximately 20°C by immersion in an ice bath and then sonicated (with a Frontline sonicator, India) at an amplitude of 90 pm and a frequency of 20 kHz to produce a uniform dispersion. The ultrasound probe was submerged to a depth of 20 mm in the samples. The sonication was done in a succession of 60 seconds with a pause of 30 seconds after each cycle for 10 minutes. The resultant pre-concentrate was lyophilized (Heto power dry LL 3000 Lyophilizer, Germany) to get Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s. All the particle characterizations of Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s were performed post lyophilization. Similarly, Nanostructured Lipid Carriers (NLC)s without Triamcinolone acetonide (TA) were also prepared following the same method for an in-vivocomparative study.
[0027] Carbopol was used to develop a homogenous gel system for the preparation of the hydrogel matrix containing Triamcinolone acetonide (TA) Nanostructured Lipid Carriers (NLC)s. For the most part, the carpool dispersion (1 percent w/v) was produced by dissolving it in distilled water until the polymer was completely wetted out, which took about an hour. A 3.5 percent v/v glycerin of the total aqueous dispersion was introduced to this polymer solution to achieve a final aqueous dispersion. Following that, Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s was added to the polymer solution to get the desired dispersion of the solute. Thereafter, 30 minutes were spent stirring the dispersed mixture at 800 rpm to achieve the desired homogeneity of the Triamcinolone acetonide (TA) Nanostructured Lipid Carriers (NLC)s hydrogel. The developed hydrogel was neutralized (pH 5.8-6.5) by gentle addition of triethanolamine with continuous stirring for 15-20 minutes.
[0028] Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s were formulated using the melt dispersion technique and then optimized using statistical design. Following that, the optimized formulation was put into several in-vitro investigations for subsequent evaluation. According to the results of the DLS experiments done on an optimized batch of Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s, mean PS and PDI were 168.9±4.32 nm, 0.247±0.82], respectively. It was discovered that the zeta potential was -26.6 4.35 mV. A higher zeta potential value (positive or negative) in the picked batch implied the formation of a stable formulation because strongly charged particles avoid the accumulation of particles due to the electric repulsion. A lower zeta potential value (negative or positive) in the chosen batch implied the fabrication of a stable formulation because highly charged particles avoid the accumulation of particles due to the electric repulsion. The %EE and % DL of the optimized Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s were calculated to be 81.121.87% and 21.61.32%, respectively. The lipophilic character of the medication, which ensures a stronger affinity for the selected lipid matrix, might be a contributing factor to the significant entrapment.
[0029] To identify the behaviour and characteristics of Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC) hydrogel, multiple tests were performed on the composition. To study Rheological behaviour, the rheology of the developed hydrogel was determined at 25 degrees Celsius using a rheometer.
[0030] The sheer pressure testing was used to assess the rheological characteristics of Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s hydrogels as well as Plain Triamcinolone acetonide (PTA) hydrogels. The sheer pressure testing process ranged from 80 to 250 Pa in 60 points with a 10 s equilibration interval at each point. This proposed that both the shear rate (1/s) and the viscosity as a module of shear pressure (Pa) are significantly higher in comparison to the baseline. A comparison of the Ostwald and Bingham model [Eq. 2 and 3] with the programs was adopted that it offered the best fit [24]. T = K y .......................................... (2) T =To + 7 .............................. (3)
where to denotes the yield pressure, r denotes the viscosity, n denotes flow index, K is the consistency index, - denotes the sheer pressure, and y denotes the shear rate.
[0031] The spreadability of hydrogel was estimated by applying a parallel plate technique with few modifications[25]. An amount of sample equal to 500mg was put to the bottom surface of the device to get a homogeneous layer of the formulation. After that, a 5 g weight was placed on the pan, previously tied to the top slide. The time taken for the top plate to move across the length of the bottom plate was measured in seconds, and the result was reported. The spreadability refers to the easiness with which a formulation may be smeared to the skin. Afterwards, spreadability was estimated by applying the stated formula: S=M.L/T Where, S = Spreadability M= Weight tensed to the upper slide L= Length of the glass slide T= Time taken to separate the slide from each other Unit =g.cm/sec
[0032] The dialysis membrane technique was used to evaluate the in-vitro release of Triamcinolone acetonide (TA) from Triamcinolone acetonide (TA) Nanostructured Lipid Carriers (NLC)s dispersion, PTA, and Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s hydrogel in a controlled environment. To determine drug release, a dialysis bag (D9652 1OOFT, Sigma-Aldrich) was loaded with 1ml of Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s dispersion and 1ml of Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s hydrogel, individually. Subsequently, PTA hydrogel (drug equivalent to 1 mg) was placed in a vial containing 10 ml of release buffer. When it comes to releasing medium, a 70:30 combination of phosphate buffer saline (PBS, pH 5.8) and methanol (70:30 v/v) was used. Vials were placed on a shaking bath at 85 rpm and 37 degrees Celsius. 1 ml of the sample was taken out from the receptor part and supplanted with an equal quantity of fresh release media at a regular interval (1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours). In the case of Triamcinolone acetonide (TA), the validated UV-spectrophotometry technique was used to estimate the amount of medication at 239 nm that was released. The final results were the mean of three different estimations. The curve-fitting approach was used to determine the release profiles of Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s dispersion, PTA, and Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s hydrogel, among other things.
[0033] Triamcinolone acetonide (TA)-Nanostructured Lipid Carriers (NLC)s hydrogel has the potential to correct the phenotypic features of psoriatic skin by facilitating the conveyance of antipsoriatic medicines over the epidermal barrier and restricting their distribution to the dermis layer.
[0034] While there has been illustrated and described embodiments of the present invention, those of ordinary skill in the art, to be understood that various changes may be made to these embodiments without departing from the principles and spirit of the present invention, modifications, substitutions and modifications, the scope of the invention being indicated by the appended claims and their equivalents.
[0035] The accompanying drawings, which are incorporated in and constitute a part of this disclosure, illustrate an exemplary embodiment and, together with the description, explain the disclosed embodiment. In the figures, the left and rightmost digit(s) of a reference number identify the figure in which the reference number first appears. The same numbers are used throughout the figures to reference features and components. Some embodiments of the system and methods of an embodiment of the present subject matter are now described, by way of example only, and concerning the accompanying figures, in which:
[0036] Figure - 1 illustrates the Invitro and Exvivo Characterization of the formulation. (i) Rheological Evaluation, A. Shear rate against Shear stress plot for TA-NLCs and plain hydrogel; B. Viscosity against Shear stress plot for TA-NLCs and plain hydrogel; (ii) In vitro release study of TA from PTA gel, TA-NLCs dispersion, and TA-NLCs gel; (iii) Drug distribution experiments depicting the quantity of TA (pg/cm 2)delivered from PTA gel and TA-NLCs gel into various parts of the skin and the receptor compartment.
[0037] Table 1.Scheme of Box-Behnken design for optimization of TA-NLCs with their experimental variables and responses.
[0038] Table 2. The in-vitro release findings for developed formulations.
Claims (4)
1. A method of synthesis of Nanostructured Lipid Carriers (NLC) encapsulated with Triamcinolone acetonide (TA) for treating proliferative skin diseases like psoriasis.
2. The method of synthesis as claimed in claim - 1, in the making docosahexaenoic acid (DHA) has been employed to play a dual role as formulation ingredient of Nanostructured Lipid Carriers (NLC) as well as to exhibit anti-inflammatory activity.
3. The method of synthesis as claimed in claim - 1, for effective transepidermal delivery, the synergistic potential of the omega 3 fatty acid-based Triamcinolone acetonide (TA)-loaded Nanostructured Lipid Carriers (NLC) system is used.
4. The method of synthesis as claimed in claim - 1, the Nanostructured Lipid Carriers (NLC)s is further integrated into a hydrogel matrix to get a longer contact time
& for easy topical application, proper spreading, and absorption on the skin.
SIGNATORY
Manju Rawat Singh
Deependra Singh
K.K.Sahu
Madhulika Pradhan
Krishna Yadav
Sheet 1 of 3
APPLICANT 23 Aug 2021
Manju Rawat Singh Deependra Singh K.K.Sahu Madhulika Pradhan Krishna Yadav 2021106678
Figure – 1
SIGNATORY
Manju Rawat Singh
Deependra Singh
K.K.Sahu
Madhulika Pradhan
Krishna Yadav
Sheet 2 of 3
APPLICANT 23 Aug 2021
Manju Rawat Singh Deependra Singh K.K.Sahu Madhulika Pradhan Krishna Yadav
Formulation Coded value of variables Response values code X1 X2 X3 Particle size Entrapment efficiency (nm) (%) F1 -1 1 0 289.17 ± 1.53 78.21 ± 0.85 2021106678
F2 1 0 1 308.32 ± 5.25 71.23 ± 0.94 F3 0 0 0 257.31 ± 3.59 74.63 ± 1.46 F4 0 0 0 255.13 ± 4.47 76.91 ± 0.99 F5 0 -1 1 204.32 ± 8.55 65.21 ± 1.33 F6 0 0 0 249.18 ± 5.69 73.23 ± 0.67 F7 0 1 -1 168.91 ± 5.42 80.82 ± 0.90 F8 1 1 0 324.83 ± 4.35 75.68 ± 0.75 F9 0 0 0 233.25 ± 0.89 76.12 ± 0.77 F10 0 1 1 214.32 ± 8.65 81.14 ± 1.18 F11 1 -1 0 304.11 ± 9.60 71.32 ± 0.75 F12 1 -1 0 306.14 ± 7.89 70.17 ± 0.98 F13 0 0 0 239.22 ± 6.28 77.14 ± 0.85 F14 1 0 -1 314.35 ± 6.10 75.69 ± 0.83 F15 -1 0 1 275.14 ± 5.93 73.21 ± 0.82 F16 -1 0 -1 235.35 ± 5.76 69.12 ± 0.80 F17 0 -1 -1 232.32 ± 5.59 73.22 ± 0.78
Independent variables Levels -1 0 +1 X1 = CSA: DHA 1:1 2:1 3:1 X2 = CS: CCS 1:2 2:2 3:2 X3= Amount of drug (w/v) 0.025 0.050 0.075 Dependent variables Constraints Y1 = Particle size (PS) Minimize Y2 = Entrapment efficiency (%EE) Maximize Where, X1 = Ratio of solid to liquid lipid, X2 = Ratio of surfactant concentration: Co-surfactant concentration and X3 = Amount of drug (w/v)
Table – 1
SIGNATORY
Manju Rawat Singh
Deependra Singh
K.K.Sahu
Madhulika Pradhan
Krishna Yadav
Sheet 3 of 3
APPLICANT 23 Aug 2021
Manju Rawat Singh Deependra Singh K.K.Sahu Madhulika Pradhan Krishna Yadav 2021106678
Formulation The correlation coefficient (R2) Slope Value Korsmeyer- Higuchi Model Korsmeyer- Higuchi Model Peppas model Peppas model TA-NLCs 0.9528 0.9173 0.3167 7.2367 TA-NLCs gel 0.8926 0.9063 0.3706 5.6911
Table - 2
SIGNATORY
Manju Rawat Singh
Deependra Singh
K.K.Sahu
Madhulika Pradhan
Krishna Yadav
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