WO2023131835A1

WO2023131835A1 - Psyllium formulation with delayed gelation property

Info

Publication number: WO2023131835A1
Application number: PCT/IB2022/061967
Authority: WO
Inventors: Rajat Shah; Vishal Shah; Shajahan Abdul
Original assignee: Inventia Healthcare Limited
Priority date: 2022-01-04
Filing date: 2022-12-09
Publication date: 2023-07-13

Abstract

The invention relates to granular psyllium formulation comprised of 10 to 60% by weight of gelation retardant, which exhibits delayed gelation property. The invention also relates to the process for preparation of granular formulation, wherein psyllium husk is treated with at least one gelation retardant and optionally one more excipient, using suitable granulation process. The formulation may be comprised of granules of varying particle size, ranging in size between 50 to 1000 microns. The granular formulation is readily dispersible with the liquid medium and maintains the viscosity of dispersion system below 1000 cP, thus making the administration convenient to the subjects in need thereof for use as a mild laxative and for the bulk formation in constipation and related conditions.

Description

Title: Psyllium formulation with delayed gelation property

Field of The Invention

The invention relates to a psyllium formulation which exhibits delayed gelation property. More specifically, the invention relates to the psyllium formulation comprised of about 10 to 60% by weight of at least one gelation retardant or the combination thereof, which delays the gelation in liquid medium and maintains viscosity of the dispersion below 1000 cP till the time of administration by the subject. The formulation may be optionally comprised of at least one excipient acceptable in nutraceutical, pharmaceutical or food industry. The invention also relates to the process for preparation of granular formulation, wherein psyllium husk is treated with at least one gelation retardant using suitable granulation process. The formulation may be comprised of granules of varying size, ranging in size between 50 to 1000 microns, which exhibit delayed gelation property. The granular formulation, as described herein, is readily dispersible with the liquid medium, and maintains viscosity of the dispersion medium within the acceptable limits, thus making the administration convenient to the subjects. Psyllium formulation exhibits delayed gelation property, thus enhancing the compliance in the subjects in need thereof.

Background

Psyllium, also referred to as Ispaghula, is derived from the husks of the seeds of Plantago ovata, which is a native herb from regions of Asia, Europe, and North Africa. It is comprised of a gel forming mucilage, which is an adhesive gelatinous substance like natural gums. Seed husk is also a rich source of water-soluble fiber, known as psyllium hydrocolloid or psyllium seed gum. Psyllium has been traditionally used in China and India as herbal medicine to treat bladder problems, high blood pressure and for treatment of skin irritations. Psyllium has also been reported to possess cholesterol-lowering abilities as well as wound healing properties. It is being utilized as part of many colon cleansing programs because of its bulk forming property and even in the prevention of colon cancer. The seed husks of psyllium commonly used as a laxative and to promote regular bowel function due to its swelling property. Psyllium seed husks promote taxation partially by increasing the mass and moisture content of the stool. Additionally, the excreta of animals and humans fed diets containing psyllium seed husk is gelatinous. This gelatinous property contributes to laxative properties of psyllium seed husks by decreasing friction in the gut. Observed increases in fecal mass and water retention also have been attributed to this gelatinous material.

The husk has been incorporated into variety of food products such as cookies, crackers and biscuits; however, these products have certain disadvantages, such as the tendency to begin to gel unpleasantly in the mouth. More precisely, psyllium seed husks can swell in the esophagus, producing an esophageal obstruction that can cause choaking. For this reason, psyllium seed husk preparations are not recommended for ingestion by persons who may have difficulty swallowing (e.g., elderly persons, children or those with specific health issues such as dysphagia condition). Finally, the recommended daily dose of psyllium husk of 3.5 - 11 g per day is inconvenient to ingest in any form and therefore there is a need to design the formulations comprising psyllium husk in a form that is convenient and pleasant to use.

Laxative preparations of psyllium seed husks are generally composed of ground husk and have coarse and unpleasant mouthfeel when administered in drinks. Psyllium forms a gelatinous mass on contact with water, and it exhibits poor dispersibility and mixability in water. Once dispersed in the aqueous solution, the psyllium husk begins to gel with an accompanying increase in the viscosity of the drink solution. Typically, the consumer of the psyllium husk suspension has to drink the liquid suspension within 5 minutes to avoid a drink with high viscosity, which becomes too thick and difficult to drink, which is aesthetically unacceptable in the subjects.

The palatability of psyllium-containing products varies depending on the form used, and, of course, the user's particular preference. Frequently, however, psyllium containing products are viewed as having poor palatability. Psyllium-containing products to be mixed with a liquid to form a drink are considered by many to be aesthetically objectionable for one or more of several reasons such as texture (e.g., grittiness, general mouth feel), viscosity, visual appearance, etc. Therefore, improving the palatability of psyllium containing products by controlling gelation rate is a continuing need which would benefit a significant number of consumers., even those who are suffering from dysphagia conditions. More palatable products may result in improved compliance for dosing regimens involving several doses or extended duration therapy.

The efforts are being taken in designing the palatable formulations of psyllium and these are reflected in the patent and literature references. The prior art patent applications aim to control the rate of gelation by using acids to reduce the pH of the drink mix solution. However, typical acids can impart too strong a taste (e.g., a sour or bitter, especially at higher levels which may be desired to maximize the reduction in gelation rate) to the solution, and this must be consistent with the flavor system being used. Obviously, such an acidic medium is not suitable for flavor systems which require neutral or basic conditions. Also, except in certain controlled circumstances, acids are not suitable for use in unflavored systems.

By reducing the psyllium husk particle size, it is possible to eliminate the gritty texture of the psyllium husk yet maintain efficacy. However, the smaller the particle size of the psyllium husk, the more the rapid gelation rate is a consumer noticeable concern.

Dispersibility and mixability of psyllium husk in aqueous solutions have been shown to be improved by utilizing higher levels of sugar. However, it is not advisable to have sugar solution as psyllium husk is recommended for diabetic patients.

US patent 5445831 describes a dispersible psyllium husk composition comprising small particle size of psyllium husk distributed in a carrier system which comprises of sugar, maltodextrin, citric acid, flavoring agents, coloring agents, and combinations thereof.

US patent 5234687 relates to psyllium husk containing unflavored drink mix compositions which consist of small particle size psyllium husk comprising less than about 10% of psyllium husk having particle sizes larger than about 60 mesh screen. The composition consists of sugar and less than 2% of edible acid, which avoids raid gelling of psyllium husk.

US patent 6133237 relates to psyllium compositions comprising acid (e.g., citric acid) and less water- soluble base (e.g., calcium carbonate agglomerated with maltodextrin) to form the granulates. This is especially preferred when small particle size psyllium husk is utilized, when the pH of the drink mix in water is elevated and/ or when the composition is prepared as an unflavored composition.

US patent 5340580 describes maltodextrin-containing agglomerates of psyllium husk comprising citric acid uniformly dispersed throughout the maltodextrin coating. This agglomerated psyllium husk has improved mixability and dispersibility in liquids because edible acid is dispersed uniformly throughout the agglomerating material coating on psyllium husk.

Some of the marketed psyllium products make use of effervescent granules containing citric acid and carbonate salts (e.g., potassium bicarbonate; sodium bicarbonate; and/or calcium carbonate) which generate carbon dioxide upon mixing with water, which assists in the mixing process. The resulting product has a distinct tart/sour taste which is incompatible with the flavors used (lemon-lime; orange).

Korean patent application 2017116692 discloses a process of treatment of psyllium husk powder with xylitol by preparing liquid xylitol, introducing psyllium husk powder and xylitol into mixer, stirring and coating, performing secondary coating using chicory extract and cellulose derivative.

US patent 8895085 discloses a psyllium husk impregnated with thin layer of oil and then oil impregnated psyllium husk is coated with agglomerating material such as hydrolyzed starch oligosaccharide, monosaccharide, disaccharide, polyglucose, polymaltose, maltodextrin or the mixture. Agglomerating material helps to improve dispersibility of the product in the vehicle, however use of oil as impregnating material results in the oily after-taste or feel in the mouth which hampers the acceptance by the subjects.

Korean patent application 2005119964 claims a composition, wherein psyllium husk is coated with suitable excipient such as oatmeal, the rice flour, the wheat flour, the barley meal, the brown rice powder, the glutinous rice flour, the com flour, the potato flour, the sweet potato flour, the bean flour. The coating avoids swelling of psyllium in the mouth, also the coating material is selected in such a way that it doesn’t impart grittiness in the mouth.

There continues to be a need for psyllium husk drink mix compositions having longer or delayed gelation time and improved aesthetics, which would enhance the compliance and convenience for the subjects in need thereof. These formulations should be easily dispersible in liquid medium and should develop the viscosity within acceptable limits, so that it will be easy to swallow by subjects of all age groups and also the subjects who are facing problems like dysphagia, which is difficulty in swelling due to variety of reasons.

Summary

The researchers of the present invention have carried out extensive work for selection of the suitable excipients in optimum amounts, which can be used in psyllium formulation, to delay or prolong the gelation time, improve the aesthetics and convenience in the subjects in need thereof. It has been surprisingly found that treatment of psyllium husk with optimum amount of at least one gelation retardant has resulted in the formulation comprised of mixed population of granules belonging to two different size range, which exhibits longer or delayed gelation time and maintains viscosity of the dispersion medium below 1000 cP till the time of administration by the subject. The granular formulation is having larger particles than unformulated psyllium husk. The formulation may be comprised of about 10 to 60% by weight of at least one gelation retardant or the combination thereof.

Granular psyllium formulation prevents the formation of immediate gelatinous mass of psyllium husk in liquid medium and it exhibits good dispersibility and mixability in the said medium for a longer time. The larger particle size of granular psyllium husk, which is less readily suspended, gets settled to the bottom of the glass, exhibits improved aesthetics such as lower viscosity, due to delayed or longer gelation rate, till the last portions of the drink. The smaller size population of granules are more readily suspended, thus exhibiting improved aesthetics in the liquid suspension having a relatively higher gelation rate than larger particles. Thus, the different particle size of formulated psyllium husk improves aesthetics, including texture, mouth feel, palatability, grittiness, and/or visual appearance, resulting into improved palatability and compliance in the subjects in need thereof, for use as a mild laxative and for the bulk formation in constipation and related conditions.

Objectives

The main objective of the present invention is to provide a granular psyllium formulation which exhibits delayed gelation property.

Other objective of the invention is to provide psyllium formulation comprised of about 10 to 60% by weight of at least one gelation retardant or the combination thereof.

Still one more objective of the invention is to provide psyllium formulation which delays the gelation in water and maintains viscosity of the dispersion below 1000 cP over a duration of 30 minutes, making it convenient for administration by the subject.

One more objective of the invention is to provide psyllium formulation which may be optionally comprised of at least one excipient acceptable in nutraceutical, pharmaceutical or food industry. Another important objective is to provide process for preparation of granular formulation, wherein psyllium husk is treated with at least one gelation retardant using suitable granulation process.

One more objective of the invention is to provide psyllium formulation comprised of granules of varying particle size, ranging from about 50 to 1000 microns, preferably in the range of 100 to 800 microns.

One important objective is to provide a granular formulation, which is readily dispersible with the liquid medium, and maintains viscosity of the dispersion medium within the acceptable limits, thus making the administration convenient to the subjects of all age groups in need thereof. Such formulation should be useful to even those subjects who are having difficulty in swelling.

One more objective of the present invention is to provide psyllium formulation for oral administration, which exhibits longer gelation time and improved aesthetics, including texture, mouth feel, palatability, grittiness and/or visual appearance, thus enhancing compliance in the subjects, for use as a mild laxative and for the bulk formation in the condition of constipation.

Detailed Description

The present invention relates to psyllium formulation comprising at least one gelation retardant or the combination thereof. The formulation is comprised of mixed population of granules ranging in size from 50 to 1000 microns. The granular formulation is readily dispersible with the liquid medium and remains suspended for longer time, thus making the administration convenient to the subjects of all age groups. The formulation may be optionally comprised of at least one excipient, acceptable in nutraceutical, pharmaceutical or food industry. The invention also relates to the process for preparation of granular formulation, wherein psyllium husk is treated with at least one gelation retardant using suitable granulation process. The psyllium formulation, comprised of granules of varying size, exhibits delayed gelation property. The psyllium husk powder used in the present invention is from psyllium seeds, from plants of the Plantago genus. Various species such as Plantago lanceolate, P.ruqelii, and P.major are known. Commercial psyllium husk includes the French (black; Plantago indica), Spanish (P. psyllium) and Indian (blonde; P. ovata). Indian psyllium husk is preferred for use herein. Also preferred is psyllium husk which is at least about 85% pure, more preferably at least about 90% pure, and most preferably at least about 95% pure.

The psyllium husk is obtained from the coat of the psyllium seeds. It is typical to remove the seed coat from the rest of the seed by, for example, slight mechanical pressure, and then to use only the seed coat. The husk powder is pale buff in colour and lacks any specific odour. The particle size of the psyllium husk (unformulated) as used herein is such that more than 95% of the particles pass through 250 microns sieve.

The formulation, as described herein, preferably contains from about 20% to about 95%, more preferably from about 30% to about 90%, of psyllium husk.

The term ‘gelation retardant’ as used herein relates to the polymeric excipient, which aids in prolonging the gelation rate of psyllium granules. The gelation retardant is used to treat, coat or granulate the psyllium husk particles, such that the granules exhibit delayed or longer gelation time, after dispersing in the liquid medium. The gelation retardant allows the viscosity of the dispersion medium to be maintained below 1000 cP over a period of 30 minutes, which is considered to be the maximum time of consumption by the subject in the home or hospital set-up, thus offering the convenience for administration and for enhancing the palatability. The excipient is insoluble in water and forms the coating over psyllium husk, which prevents immediate gelation of psyllium husk on contact with water and it exhibits good dispersibility and mixability in water.

The formulation with limited viscosity is useful to the subjects who are suffering from dysphagia which is the medical term for swallowing difficulties. According to the information by National Dysphagia Diet Task Force (NDDTF), four level of thickened liquids were decided based on measurement of viscosity (thin, nectarlike, honey-like, and spoon-thick). Viscosity describes a liquid’s thickness -more specifically its resistance to flow and is reported in centipoise (cP). Viscosity ranges for the NDD liquid categories are: thin (1-50 cP), nectar-like (51-350 cP), honey-like (351- 1,750 cP), and spoon-thick (greater than 1,750 cP). The viscosity limit acceptable for a drink formulation should be ideally the one which represents the viscosity of honey, so that it will not cause any choaking hazards in the subjects of all age groups, or even in those who might be suffering from dysphagia like conditions.

The formulation of the present invention exhibits viscosity of dispersion in water or any other suitable liquid medium, which is preferably about 5 to 1500cP and more preferably about lOOOcP, which is a drinkable viscosity as compared to unformulated Psyllium Husk, which may exhibit viscosity of about 5000 cP after dispersion in liquid medium. According to the important embodiment of the present invention, at least one gelation retardant may be selected from the group of, but not limited to cellulose polymers and derivatives, phthalic acid and succinic acid derivatives of cellulose, starch derivatives and modified starch polymers, acrylic and methacrylic copolymers, maleic copolymer, maleic copolymer, amylose acetate phthalate, polyvinyl derivates, alginates and the combination thereof.

Cellulose based gelation retardant can be selected from hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, hydroxymethyl ethylcellulose phthalate, cellulose acetate, cellulose acetate phthalate, cellulose acetate succinate, cellulose acetate maleate, cellulose acetate phthalate, cellulose acetate succinate, cellulose acetate maleate, cellulose acetate trimelliate cellulose benzoate phthalate, cellulose propionate phthalate, methylcellulose phthalatem carboxymethyl ethyl cellulose, sodium carboxymethylcellulose cellulose acetate, ethyl hydroxyethyl cellulose phthalate and the combination thereof. Acrylic and methacrylic acid copolymer based gelation retardant can be selected from styrene, acrylic acid copolymer, methyl acrylate-acrylic acid copolymer, methyl acrylate methacrylic acid copolymer, butyl acrylate styrene acrylic acid copolymer, methacrylic acid methyl methacrylate copolymer (e.g. Trade-names: Eudragit L 100 and Eudragit S, available from Rohm Pharma), methacrylic acid ethyl acrylate copolymer (e.g. Trade- name: Eudragit L 30-D 55, available from Rohm Pharma), methyl acrylate- methacrylic acid octyl acrylate copolymer and combination thereof.

Maleic copolymer-based gelation retardant include vinylacetate maleic acid anhydride copolymer, styrene maleic acid anhydride copolymer, styrene maleic acid monoester copolymer, vinyl ethylether maleic acid anhydride copolymer, ethylene maleic acid anhydride copolymer, vinylbutylether maleic acid anhydride copolymer, acrylonitrile, methyl acrylate maleic acid anhydride copolymer, butyl acrylate, styrene maleic acid anhydride copolymer and combination thereof.

Polyvinyl derivative-based gelation retardant include polyvinyl acetate, polyvinyl alcohol phthalate, polyvinyl acetate phthalate, polyvinyl butylate phthalate, polyvinyl acetoacetic phthalate and combination thereof.

Among these examples, gelation retardant selected from starch derivatives, acrylic copolymer and polyvinyl derivates, either alone or in combination, are preferable for treating psyllium husk particles to get granules of varying particle size, to achieve longer gelation time.

Starch is a carbohydrate polymer consisting of a large number of glucose units linked together primarily by alpha 1 -4 glucosidic bonds. The starch polymers come in two forms: linear (amylose) and branched through alpha 1-6 glucosidic bonds (amylopectin), with each glucose unit possessing a maximum of three hydroxyls that can undergo chemical substitution. Starch acetate is a modified starch, which may be obtained by esterification of food starches with acetic anhydride or vinyl acetate in accordance with good manufacturing practice. The esterification/acetylation results in substitution of hydroxyl groups with acetyl esters. Starch acetate may additionally be subjected to acid, alkali, enzyme, or bleaching treatment for proposed use in nutraceutical, food or pharmaceutical industry.

In principle, all starches, selected from native barley, oats, wheat, potato, tapioca and corn starch are suitable for the preparation of formulation according to the present invention, but acid hydrolysed starches are especially suitable for the preparation of the formulation according to the present invention. It is, however, especially preferable to use the starch acetate in the form of modified starch or chemically modified food starch refined from tapioca, for the purpose of present invention.

Another preferred polymeric gelation retardant suitable for the preparation of psyllium formulation with delayed gelation rate, according to the present invention, is selected from polyvinyl acetate based dispersion. Polyvinyl acetate based polymeric excipient may be also used in modified release formulations in the form of coat or matrix for the active ingredient.

As per one more embodiment, preferred polymeric gelation retardant may also be selected from methacrylic acid copolymers, such as methacrylic acid- ethyl acrylate copolymer, which may be available in the form of aqueous coating dispersion.

The gelation retardant as used according to the present invention may be polymeric or non-polymeric in nature, although the polymeric gelation retardant is preferred for the purpose of the formulation described herein.

According to one embodiment of this invention, the polymeric gelation retardant may be used in the range of 5 to 65% by weight of the psyllium formulation. More preferably, the gelation retardant may be used in the range of 10 to 60% by weight of the formulation. The term ‘delayed gelation’ as used in the present invention may relate to the phenomenon, by virtue of which the formulated psyllium exhibits slower gelation or swelling after dispersing in the liquid medium, which is beneficial for maintaining the viscosity of the resulting dispersion within the acceptable limit, thus making it convenient for administration to the subjects in need thereof. Psyllium formulation, as described herein is formulated to comprise mix population of granules of varying particle size, such that the larger particle size of granular psyllium husk will get settled to the bottom of the glass. As a result of this, the larger size granules are less readily suspended in the dispersion medium. At the same time, the granules of smaller particle size remain suspended and undergo rapid gelation on contact with liquid medium. As a combined effect of slow or rapid gelation due to difference in the granule size, the formulation results into delayed gelation, thus providing a formulation, which maintains lower viscosity (below 1000 cP) over 30 minutes, till consumption by the subjects in need thereof. The formulation thus exhibits lower viscosity values of the resulting dispersion, due to delayed or longer gelation rate, till the last portions of the drink. Granular psyllium formulation, as described herein, thus improves aesthetics, including texture, mouth feel, palatability, grittiness, and/or visual appearance, resulting into improved palatability and compliance in the subjects in need thereof.

The term ‘subjects in need thereof’ as used herein may relate to the humans, pets or livestock, while pets or livestock may be selected from the group consisting of dogs, cats, guinea pigs, rabbits, pigs, cattle, sheep, goats, horses and/or poultry. In some embodiments, the subject is a male or female subject. The subjects in need thereof may be those subjects, who are in need of use of a bulk forming agent, a mild laxative which can be used as a gut cleansing agent. The formulation of the invention comprising psyllium granules with delayed gelation property can be also used in such subjects for gaining appetite control and taking care of digestive health, to maintain or protect cardiovascular health by managing cholesterol levels as well as blood sugar levels. The subjects in need thereof can be of any age group, ranging from pediatric to geriatric group, within the scope of present invention.

As per one more embodiment of the invention, the formulation may be comprised of psyllium husk particles which is treated with gelation retardant and optionally one excipient acceptable in nutraceutical, food or pharmaceutical industry. The formulation may thus be comprised of about 0 to 30% by weight of the excipient such as carriers, diluents, sweetening agents, flavoring agents, coloring agents and the like, which are acceptable in nutraceutical and food industry, which may be added as processing aid or for facilitating the aesthetic features. These excipients may be selected by employing general understanding and science of formulation technology.

The formulation may be comprised of mixed population of granules, which may range in size varying from 50 to 1000 microns. The granular psyllium formulation, comprised of granules of varying size, exhibits delayed gelation property.

According to important embodiment of the invention, the process for the preparation of the formulation may be comprised of treating psyllium husk with gelation retardant using suitable granulation process. Psyllium husk may be mixed well with gelation retardant and optionally one excipient acceptable in nutraceutical, food and pharmaceutical industry, following which it may be granulated using sufficient amount of solvent in suitable granulating equipment. The wet mass may be dried and screened to get the granules of varying size, suitable for achieving the longer gelation time.

As per the further embodiment, the solvent used in the process for preparation of psyllium granules may be selected from the group of aqueous or organic group, such as water, alcohol, hydroalcoholic mixture, isopropyl alcohol, higher alcohols, dicholoromethane, ethyl acetate, hexane and the combination thereof. The formulation as described herein, should have residual solvents within acceptable limit, in order to be used for the subjects in need thereof.

According to one embodiment, the psyllium husk may be mixed with gelation retardant using a suitable mixer such as ribbon blender, vertical blender, tumble blender, sigma blade mixer, double planetary mixer, twin-screw continuous blender, continuous processor, cone screw blender, screw blender, double cone blender, impinging mixer, jet mixer, drum blenders and the like or the combination thereof. The blend may be granulated using sufficient amount of solvent employing process such as fluidized-bed granulation, high-shear granulation, extrusion, or other suitable wet granulation processes. The resulting wet granules can be dried and sized to get mixed population of granules, varying from 50 to 1000 microns. The process for preparation is simple, convenient, economic, and also makes use of commonly available industrial equipment.

According to one important embodiment of this invention, the formulation may be comprised of granules of varying particle size, which range in size from 50 to 1000 microns, more preferably 100 to 800 microns. The smaller and the larger granules may be mixed in various ratios in the formulation, in order to control the viscosity of the resulting dispersion in liquid medium.

The population of granules of varying size, obtained by treatment with gelation retardant, may contribute to longer gelation time. The larger particle size of formulated psyllium husk, which is less readily suspended, may result in settling down the husk, thus eventually may exhibit improved aesthetics in the form of lower viscosity. This may result into longer or delayed gelation time for the last portions of the drink when the psyllium formulation is dispersed in the liquid medium. Further, the smaller particles of formulated psyllium husk, may get suspended more readily, thus may result into relatively higher gelation rate than larger particles. Thus, mixed population of varying particle size of psyllium granules may maintain the viscosity of the aqueous system below 1000 cP till the time of administration by the subject, thus this may improve aesthetics, including texture, mouth feel, palatability, grittiness, and/or visual appearance. Granular psyllium formulation may prevent the formation of immediate gelatinous mass of psyllium husk on contact with water and it exhibits good dispersibility and mixability in water for longer time.

The granular formulation is evaluated for particle size distribution and compared with unformulated psyllium husk for comparative information on particle size before and after the formulation. The granules prepared by treatment with gelation retardant are also evaluated for gelation property and viscosity in comparison with the unformulated psyllium husk to check for the time required for gelation. Psyllium formulation, as described herein may be suspended in liquid medium such as water and can be observed for its dispersibility property and aesthetics such as texture, mouth feel, palatability and visual appearance. Viscosity of the formulation, as described herein is also evaluated in variety of liquid media to understand effect of varying pH on viscosity built- up over a period of 30 minutes, to demonstrate the convenience of the administration of the formulation of present invention in all age groups.

The granular formulation is readily dispersible with the liquid medium and remains suspended for longer time, also providing longer gelation time without forming quick gelatinous mass, thus making the administration convenient to the subjects in need thereof. The formulation as described herein can be in the form of drink mix composition comprising the granules of varying size. It can be formulated in any form suitable for mixing with a liquid to form a psyllium husk suspension for oral consumption. Psyllium formulation can be filled in sachets or suitable container as a bulk or unit dosage form for dispersing in liquid medium. The formulation can be also incorporated in other nutraceutical or food products, for gaining benefits related to its intended use. The formulation may be used in the young as well as old subjects in need thereof, who may belong to vast age group, for its application as mild laxative and for the bulk formation in the condition of constipation. The formulation may also be useful for protection and management of cardiovascular and digestive health, weight and appetite control and the related conditions.

Psyllium formulation as described herein is granular in nature and exhibits longer gelation time, which makes it palatable and convenient for administration to the subject in need thereof, belonging to all age groups. The product is designed to improve compliance and it may help to reduce the choaking hazards in the subjects who have the difficulty in swallowing because of age, other physical conditions, and illness conditions such as dysphagia. The details of the present invention are described in the Examples given below which are provided to illustrate the invention and therefore should not be construed to limit the scope of the present invention. Examples

Example 1: Psyllium granular formulation

Table 1: Composition of Formula 1

*q.s. implies quantity sufficient Process for the preparation

Psyllium husk is passed through a vibratory sifter. The mixture is then introduced in a ribbon blender. The blend is granulated using purified water and the wet granules are milled using suitable equipment. The granules are dried and screened.

The granular formulation can be suspended in suitable liquid medium and dispersed well for consumption.

Example 2: Psyllium granular formulation Table 2: Composition of Formula 2

Process for the preparation

Psyllium husk and starch acetate are passed through a vibratory sifter. The mixture is then introduced in a ribbon blender. The blend is granulated using purified water and the wet granules are milled using suitable equipment. The granules are dried and screened to obtain population of desired size. The granular formulation can be suspended in suitable liquid medium and dispersed well for consumption. Example 3: Psyllium granular formulation

Table 3: Composition of Formula 03-05

Process for the preparation of granular formulation

Psyllium husk, and gelation retardant (starch acetate or methacrylic acid-ethyl acrylate copolymer or polyvinyl acetate) are passed through a vibratory sifter. The mixture is then introduced in a ribbon blender. The blend is granulated using purified water and the wet granules are milled using suitable equipment. The granules are dried and screened to obtain population of desired size in the range of 150 to 600 micron.

Example 4: Viscosity measurement of Formula 01 to Formula 05

The granular psyllium formulation was evaluated for viscosity to determine the gelation rate and to understand the effect of gelation retardant using Brookfield DV-II+PRO viscometer. 5 gm of psyllium granular formulation was added in 250 ml water and the resulting suspension was subjected to viscosity measurement at the initial time point followed by 15mins and 30 mins respectively. Viscosity was measured in centipoise units (cP) for psyllium husk granules of Formula 1, which is devoid of any gelation retardant and the values were compared with other formulations comprising various polymeric gelation retardant excipients as documented in Table 4. Table 4: Viscosity measurement (cP) using Brookfield viscometer

Once dispersed in the aqueous system, Formula 1 begins to gel in gradual manner with an accompanying increase in the viscosity of the resulting drink suspension. Typically, the subject may consume the suspension over a relatively long period of time (more than about thirty minutes) in hospital set-up or even at home. The viscosity built-up in Formula 1 aqueous system was found to be about 5300 cP, while the viscosity measurement for Formula 02 to Formula 05 was significantly less, ranging from 118 to 1345 cP. Thus the viscosity for unformulated psyllium husk was significantly higher than the formulated psyllium husk comprising at least one gelation retardant. Treatment of psyllium husk with gelation retardant prevents formation of immediate gelatinous mass of psyllium husk on contact with water and it exhibits good dispersibility and mixability in water, thus enhancing the convenience of administration to the subjects in need thereof.

Example 5: Psyllium granular formulation

Table 4: Composition of Formula 06 to Formula 11 (Percent content)

Process for the preparation of granular formulation

The process of preparation is similar to the process mentioned in Example 2 wherein the psyllium husk, and gelation retardant agent along with the other excipient is passed through a vibratory sifter. The mixture is then introduced in a ribbon blender. The blend is granulated using purified water and the wet granules are milled using suitable equipment. The granules are dried and screened to obtain population of desired size in the range of 150 to 600 micron. The granular formulation can be suspended in suitable liquid medium and dispersed well for consumption.

The granular formulations were evaluated for viscosity measurement at various time points to understand the effect of addition of varying percentage of gelation retardant and optional excipients on rate of gelation process. The viscosity measurement was done at initial, 15 min and 30 min time interval. It was observed that viscosity of the resulting aqueous system was maintained between 40 to 550 cP over the period of 30 minutes.

Thus, the formulation exhibits delayed gelation property and enhances compliance in subjects of all age group, by maintaining viscosity below 1000 cP.

Example 6: Psyllium granular formulation

Table 5: Composition of Formula 12-17 (Percent content)

Process for preparation of the formulation

The process of preparation is similar to the process mentioned in example 2 wherein the psyllium husk, and starch acetate, along with optional excipient such as maltodextrin is passed through a vibratory sifter. The mixture is then introduced in a ribbon blender. The blend is granulated using purified water and the wet granules are milled using suitable equipment. The granules are dried and screened to obtain population of desired size. The granular formulation can be suspended in suitable liquid medium and dispersed well for consumption by the subject in need thereof.

The formulation was evaluated for particle size, total fiber content and the viscosity measurement and the results are documented in Table 5. The total fiber content of the psyllium formulation was found to be more than 80%.

The granular formulation is found to be comprised of mixed population of particles, which exhibit viscosity ranging from 10 to 1000 cP. The larger particle size of formulated psyllium husk (300 to 600 microns), which is less readily suspended, may result in settling down the husk, thus eventually may exhibit improved aesthetics in the form of lower viscosity (19-300 cP). This may result into longer or delayed gelation time for the last portions of the drink when the psyllium formulation is dispersed in the liquid medium.

Further, the smaller particles of formulated psyllium husk (150 to 300 microns), may get suspended more readily, thus may result into higher viscosity values (50 to 900 cP), indicating relatively higher gelation rate than larger particles. The population of granules of varying size, obtained by treatment with gelation retardant, may contribute to longer gelation time. Thus, mixed population of varying particle size of psyllium granules may maintain the viscosity of the aqueous system below 1000 centipoises till the time of administration by the subject, thus this may improve aesthetics, including texture, mouth feel, palatability, grittiness, and/or visual appearance.

Example 7: Viscosity of psyllium formulation in various liquid medium

Psyllium granular formulation (Formula 17) was subjected for dispersion in 250 ml of different pH solution and the viscosity was measured using Brookfield Viscometer at different time intervals, as shown in the table below.

Table 6: Viscosity measurement of Psyllium formulation at varying pH

It was observed that the granular psyllium formulation exhibits delayed gelation property in dispersion media irrespective of pH. Thus the formulation can be administered by dispersing in desired medium of choice, without any impact on viscosity of the resulting system, over a period of 30 minutes, thus enhancing the compliance and ease of administration.

Example 8: Psyllium formulation with optional excipients Formula no. 17 (92%w/w) was blended with optional excipients such as 4.5% edible acid (citric acid monohydrate), 1% colouring agent (Turmeric), 1.5% flavouring agent (Orange powder mix), and 1% sweetening agents (Stevia) to get psyllium formulation.

The formulation was dispersed in suitable medium, and the viscosity was measured at different time points. The initial viscosity, after 15 and 30 mins was observed to be 4.5cP,

8cP and 15cP respectively.

The granular psyllium formulation, as described herein, is readily dispersible with the liquid medium, and maintains viscosity of the dispersion medium within the acceptable limits, thus making the administration convenient to the subjects. Psyllium formulation, as described herein exhibits delayed gelation property and improved texture as well as visual appearance, thus enhancing the compliance in the subjects in need thereof.

Claims

We Claim;

1. A psyllium formulation, comprised of psyllium husk and at least one gelation retardant, wherein the formulation exhibits delayed gelation property.

2. Psyllium formulation as claimed in claim 1, which may be comprised of 40 to 90% by weight of psyllium husk.

3. Psyllium formulation as claimed in claim 1, which may be comprised of 10 to 60% by weight of at least one gelation retardant or the combination thereof.

4. Psyllium formulation as claimed in claim 1, which may be optionally comprised of at least 0-30% by weight of at least one excipient acceptable in nutraceutical, pharmaceutical or food industry.

5. Psyllium formulation as claimed in claim 3, which may be comprised of at least one gelation retardant selected from the group of, but not limited to cellulose polymers and derivatives, phthalic acid and succinic acid derivatives of cellulose, starch polymers, starch derivatives and modified starch polymers, acrylic copolymers, maleic copolymer, amylose acetate phthalate, polyvinyl derivates, ethyl cellulose, pectin, alginates and the combination thereof.

6. Psyllium formulation as claimed in claim 5, which may be comprised of at least one gelation retardant selected from the group of, but not limited to starch acetate, alginic acid, methacrylate polymers, polyvinyl acetate polymers, HPMC derivatives of succinic acids, phthalic acids, and the combination thereof.

7. Psyllium formulation as claimed in claim 1, which may be comprised of mixed population of granules varying in the range of 100 to 800 microns.

8. Psyllium formulation as claimed in claim 1, which is readily dispersible in liquid medium, exhibits delayed gelation property and maintains viscosity of the resulting dispersion medium below 1000 cP till the time of administration, thus enhancing convenience to the subjects.

9. The process for preparation of psyllium formulation, wherein

• psyllium husk is blended with at least one gelation retardant,

• the blend may be optionally mixed with at least one excipient, acceptable in nutraceutical, pharmaceutical or food industry

• the blend may be granulated and/ or coated using aqueous or hydroalcoholic solvent

25 • the wet granules may be milled using suitable equipment, followed by drying and screening to obtain granules of desired size. Psyllium formulation of claim 1, which can be filled in sachets or suitable container as a bulk or unit dosage form for dispersing in liquid medium for use in the subjects in need thereof.