DESC:FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See Section 10 and Rule 13)

Title of the Invention
PERMEATION ENHANCEMENT MATRIX COMPOSITION

Name and Address of the Applicant
ITC LIMITED
Corporate office at Thapar House, 2nd Floor, 124 Janpath, New Delhi 110001

Nationality
An Indian company

Preamble to the Description
The following specification particularly describes the invention and the manner in which it is to be performed.

FIELD OF THE INVENTION:
[001] The present invention relates to edible composition. More particularly the present invention relates to an edible composition comprising a permeation enhancement matrix to enhance the permeation coefficient of an active and a method thereof.
BACKGROUND OF THE INVENTION:
[002] In the field of pharmaceutical, nutraceutical, and consumer health products, there is an ongoing need to improve the permeation of active ingredients administered through non-invasive routes such as oral, buccal, and sublingual delivery. These routes offer several advantages over traditional oral dosage forms, including rapid onset of action and avoidance of first-pass metabolism. However, the primary challenge with these routes is the low permeability of certain active ingredients, particularly those that are temperature-sensitive or have limited solubility.
[003] The sublingual and buccal routes have been explored as alternatives to traditional oral administration due to their potential for rapid onset of action. However, these methods still suffer from limited permeation capabilities. Current approaches to improving permeation include the use of lipophilic agents, dehydration techniques, lyophilization, or complex formulation processes involving multiple steps that may not be suitable for all active ingredients.
[004] Several actives in existing edible compositions such as pouches, snus, snuff, lozenges, film, gum, chewing gum, tablets, strips, capsules, caplet, spray, food and combinations thereof, and non-edible formulations such as patches, nasal, etc., with actives which are naturally/synthetically derived, have low permeation coefficient. The sublingual and buccal routes of administration are an effective alternative to the traditional oral route and may be useful for users who might have some swallowing difficulties. Even though these routes have significant advantages over the other forms for superior delivery of active by providing fast onset of action, they suffer from suboptimal permeation.
[005] Several prior art documents disclose formulations aimed at enhancing permeability:
[006] WO2019245639A1: describes a process for making an edible product infused with a lipophilic active agent with enhanced delivery across the blood brain barrier in a subject, comprising: providing a therapeutically effective amount of a lipophilic active agent; providing a bioavailability enhancing agent; providing an edible substrate; contacting the edible substrate with an oil comprising the lipophilic active agent and the bioavailability enhancing agent; and dehydrating the edible substrate. The bioavailable enhancing agent comprises an edible oil comprising long chain fatty acids and/or medium chain fatty acids that enhance the bioavailability of the lipophilic active agent and enhance delivery across the blood brain barrier in the subject. Although effective for certain applications, this approach primarily relies on lipid-soluble actives and involves dehydration steps, which may not be suitable for temperature-sensitive compounds. Moreover, dehydrating step may adversely affect moisture-sensitive actives or ingredients during drying process due to the long period of exposure with moisture during combined water-thermal treatment.
[007] US11700875B1: titled “compositions and methods for sublingual delivery of nicotine” describes a composition of nicotine chosen from nicotine benzoate, nicotine polacrilex, or mixtures thereof; sunflower oil; sodium bicarbonate; and inulin, microcrystalline cellulose, or mixtures thereof; and wherein further the ratio of nicotine benzoate or nicotine polacrilex to sunflower oil is from about 1:1 to about 1:3 ingredients. The formulation includes a combination of nicotine benzoate, sunflower oil, and other excipients to enhance the absorption of nicotine. This approach is limited in scope to specific active ingredients and requires careful balancing of the formulation components to achieve the desired permeation enhancement.
[008] WO2019202396A1: Discloses enhancing the bioavailability of actives using a dehydrated powder approach. The process utilizes dehydration techniques to form a powdered product that can be reconstituted to enhance permeation. While dehydration can improve shelf life, it can also compromise the stability of certain temperature-sensitive actives during the preparation process. Moreover, dehydrating step may adversely affect moisture-sensitive actives or ingredients during drying process due to the long period of exposure with moisture during combined water-thermal treatment.
[009] Despite these advancements, the preparation techniques used are either complex or energy intensive that may adversely affect temperature-sensitive or moisture- sensitive ingredients. Hence, there remains a need for a more efficient, scalable, and less intensive process for enhancing the permeation of active ingredients while maintaining stability during manufacturing and storage.
[010] Existing methods, including those mentioned above, involve either complex multi-step processes such as lyophilization or dehydration, or rely on specific lipid carriers, which may limit the types of actives that can be incorporated. Furthermore, the need for thermal processing during preparation can degrade temperature-sensitive ingredients, reducing their efficacy. So there remains a need for a formulation that can effectively enhance the permeation of a wide range of active ingredients, including temperature-sensitive compounds, without relying on energy-intensive dehydration or high thermal processes.
[011] An improved composition should provide a scalable manufacturing process, maintain the stability of the active ingredients, and facilitate rapid and efficient delivery of the actives through non-invasive routes such as buccal and sublingual administration.
[012] Present inventors have formulated prosomes which are free-flowing granular products like solid particles/powder that have the potential to form liposome in a self-assembly matrix upon hydration or contact with water. Preparation of such prosomes involves a non-aqueous-based slurry and mild thermal route which provides a less energy-intensive process. This results in prosomes that are stable during while storage. It is advantageous to prepare prosomes with temperature-sensitive or moisture-sensitive active ingredients using the present process.
OBJECTIVE OF THE INVENTION:
[013] It is an object of the present invention to overcome the limitations associated with existing lyophilization or dehydration-based techniques.
[014] It is another object of the present invention to provide a free-flowing prosome composition comprising an alkaloid resin and a permeation enhancement matrix. To provide a composition that enhances the permeability of active substances through a non-aqueous, mild to moderate thermal preparation method.
[015] It is another object of the present invention to enable the preparation of a composition that can be used in edible formats like pouches, gums, tablets, caplets, capsules and other delivery forms.
[016] It is yet another object of the present invention to provide an easily scalable method for the preparation of said prosome composition which is a non-aqueous based slurry approach using rotary evaporation.
[017] It is yet another object of the present invention to provide a prosome composition that is thermally stable and has a high entrapment efficiency.
[018] It is yet another object of the present invention to provide a prosome in various forms of active (for example alkaloid resin, alkaloid salt) that exhibits a higher permeation coefficient factor.
[019] It is yet another object of the present invention to provide an edible composition to increase the permeation coefficient of an active substance.
[020] It is yet another object of the present invention to provide a permeation enhancement matrix composition.
SUMMARY OF THE INVENTION:
[021] The present invention herein relates to a composition, comprising prosomes a type of free-flowing granular product. These prosomes have the ability to form liposomes spontaneously in a self-assembly matrix upon hydration or contact with water. The composition of the present invention includes a permeation enhancement matrix, incorporating a lipid matrix, at least one solvent, and suitable excipients. The lipid matrix consists of saturated and unsaturated fatty acids or esters. The active ingredient, which can be naturally and/or synthetically derived alkaloids or other temperature-sensitive actives, is present in an amount up to 75% by weight of the prosome formulation.
[022] The method of the present invention includes a non-aqueous-based slurry approach using rotary evaporation for the scalable preparation of the prosome composition. The process includes the steps of providing an active ingredient, a lipid matrix, and a solvent; contacting the active ingredient with the lipid matrix and solvent; and evaporating the solvent from the mixture at any of the temperature ranging from ambient temperature of 25°C to the respective boiling point temperature of the selected solvent, depending on the sensitivity of active to thermal conditions. The pressure at which the evaporation takes place at a given temperature ranges from vacuum pressure of 16 mbar to atmospheric pressure depending on the selected solvent. This results in the formation of a free-flowing prosome formulation.
[023] Upon hydration, the prosome exhibits enhanced permeability of the active ingredient buccal mode when compared against the control mode. The method offers advantages such as scalability, a non-lyophilization, a non-dehydration approach, and the ability to prepare stable prosomes with temperature-sensitive active ingredients.
DETAILED DESCRIPTION OF THE INVENTION:
[024] The present invention may be embodied in several forms, and the details of embodiments of the present invention will be described in the following content. The embodiments described below are merely illustrative of the technical solutions of the present disclosure but are not to be construed as limited to the technical solutions of the present disclosure.
[025] The terms and words used in the following description and claims are not limited to the bibliographical meanings but are merely used by the inventor to enable a clear and consistent understanding of the invention. Accordingly, it should be apparent to those skilled in the art that the following description of the present invention is provided for illustration purposes only and not for the purpose of limiting the invention as defined by the appended claims. As used in the description of the invention and the appended claims, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.
[026] Unless otherwise defined, all terms (including 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 pertains. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.
[027] The term “prosomes” refers to dry, free-flowing particles with a dispersed system that can instantaneously form a liposomal suspension upon hydration.
[028] The term, “free flowing particles” as per USP 1174 means, particles having either Hausner ratio in the range of 1.12-1.18 or compressibility index in the range of 11-15. Further, it was noted that the prosome powder upon hydration forms liposomes in less than a minute, as detected by particle size analyzer (with particle size range of 140-180 nm).
[029] In an embodiment of the invention the prosome composition includes at least one active ingredient, and the permeation enhancement matrix.
[030] As stated hereinabove, the currently available edible compositions of alkaloids, particularly the buccal and oral compositions such as pouches, snus, snuff, lozenges, film, gum, chewing gum, tablets, strips, capsules, caplet, spray, food and combinations thereof with actives which are naturally / synthetically derived, have low permeation coefficient.
[031] The suitable active ingredient is selected from naturally or synthetically derived alkaloid(s) or any suitable active(s), active with polymer/resin (e.g. alkaloid resinate), Salts (e.g. pyruvate, bitartrate, tartrate, citrate, maleate, etc) and/or a combination thereof.
[032] Actives can be selected from the group consisting of naturally or synthetically derived alkaloid such as nicotine, nicotine salt(s), nicotine polymer/resin (e.g. nicotine polacrilex), vitamin, caffeine and also any other temperature-sensitive actives.
[033] Said active ingredients can be present in an amount up to 75 % by weight; and preferably up to 37% by weight of the prosome formulation.
[034] The permeation enhancement matrix comprises a lipid matrix; at least one solvent; and suitable excipients.
[035] The lipid matrix comprises one or more saturated and unsaturated fatty acid or fatty ester. Solvents are non-aqueous and include but are not limited to various hydrocarbons (for example hexane, pentane, heptane, toluene, etc.), halogenated solvents (chloroform, dichloromethane, etc.), esters (for example ethyl acetate, propyl acetate, butyl acetate, etc.), ethers (diisopropyl ether, diethyl ether, ketones, acetone, propanone, etc.) and alcohols (ethyl alcohol, methanol, isopropyl alcohol, etc. ) One or more excipients can be selected from surfactants, fillers, carriers, and a combination thereof.
One or more saturated and unsaturated fatty acid or fatty ester can be selected from a host of medium-chain and long-chain fatty acids, or their respective esters of mono, di, tri glycerides, and combinations thereof. The group consists of medium chain saturated fatty acid C6-C10 (such as caproic acid, caprylic acid, capric acid, etc.) or long chain saturated fatty acid C12-C24 (such as lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, etc.) or long chain unsaturated fatty acid (such as oleic acid, a-linolenic acid, linoleic acid, arachidonic acid, palmitoleic acid, etc.) or their respective esters of fatty mono-, di- or tri- glycerides thereof. Preferably the lipid matrix comprises palmitic acid, lauric acid, myristic acid, palmitoleic acid, stearic acid, linoleic acid, a-linolenic acid, oleic acid and arachidonic acid and their corresponding esters.
[036] Surfactants include but are not limited to polysorbate 20 (i.e. polyoxyethylene (20) sorbitan monolaurate); polysorbate 60 (i.e. polyoxyethylene (60) sorbitan monostearate); polysorbate 80 (i.e. polyoxyethylene (20) sorbitan monooleate); and polysorbate 65 (i.e. polyoxyethylene (20) sorbitan tristearate).
[037] Fillers include but are not limited to microcrystalline cellulose (MCC), arabic gum, inulin, starch, modified starches, xanthan gum, carboxymethyl cellulose, methylcellulose, hydroxypropylmethyl cellulose, konjac, chitosan, tragacanth, karaya, ghatti, larch, carageenan, alginate, chemically modified alginate, agar, guar, locust bean, psyllium, tara, gellan, curdlan, pullan, gelatin, pectin, and combinations thereof.
[038] Carriers include but are not limited to sugar alcohols, for example, sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol, hydrogenated starch hydrolysates, isomaltose, or any combination thereof.
[039] In an aspect of the invention the composition of prosomes, which are free-flowing granular products capable of forming liposomes upon hydration, enhancing the permeability of active ingredients. The invention includes the formulation of the prosomes using a non-aqueous slurry approach and rotary evaporation to achieve a scalable, mild to moderate thermal, and non-dehydration-based preparation method suitable for temperature-sensitive or moisture-sensitive active substances.
1. Prosome Composition consists of:
Active Ingredient: The active ingredient can be naturally or synthetically derived.). The active may also be present in the form of resins or other derivatives of polymer/resin e.g., alkaloid-polacrilex or salts such as pyruvate, bitartrate, tartrate, citrate, maleate, etc. The active ingredient is present in an amount up to 75% by weight of the total composition.
Lipid Matrix: The lipid matrix comprises a combination of saturated and unsaturated fatty acids or their esters. The lipid matrix helps facilitate the formation of liposomes upon hydration, thereby enhancing the permeability of the active ingredient. The lipid matrix can constitute 10-25% by weight of the total composition.
Solvent: A non-aqueous solvent such as isopropyl alcohol, hexane, ethyl acetate or chloroform is used to prepare the slurry. The solvent aids in dissolving the lipid matrix and dispersing the active ingredient. The solvent is used in an amount sufficient to dissolve the lipid matrix and evenly distribute the active ingredient.
Excipients: Excipients may include surfactants, fillers, and carriers to stabilize the composition. Surfactants like polysorbate 80 (Tween 80) can be used to improve the dispersion of the active. Fillers such as microcrystalline cellulose (MCC), inulin, or starch may be included to improve the flow properties and handling of the formulation. Carriers like sorbitol or mannitol can be used to aid in the processing of the composition. Surfactants are used in an amount of 5–10% by weight of the total composition, fillers are used in an amount of 30–50% by weight of the total composition, and carriers are used in an amount of 10–20% by weight of the total composition.
[040] In a preferred embodiment, the prosome composition comprises
i) alkaloid resin at a weight percent of about 37%, and
ii) permeation enhancement matrix composition comprising
lipid matrix at a weight percent of about 14%,
Tween (80) at a weight percent of about 5 %, and
Microcrystalline cellulose (MCC) at a weight percent of about 44% by weight of the total composition.
Wherein, said lipid matrix composition comprises saturated fatty acid at a weight percent of about 9-90%, and unsaturated fatty acid at a weight percent of less than 10% by weight of the lipid matrix composition.
[041] Described herein is also a method for preparation of the prosome formulation comprising the steps of:
i. providing an active ingredient;
ii. providing a lipid matrix;
iii. providing a solvent;
iv. contacting the active ingredient with lipid matrix and solvent; and evaporating the solvent from the mixture at any of the temperature ranging from ambient temperature of 25°C to the respective boiling point temperature of the selected solvent, depending on the sensitivity of active to thermal conditions. The pressure at which the evaporation takes place at a given temperature ranges from vacuum pressure of 16 mbar to atmospheric pressure depending on the solvent, to obtain the free-flowing prosome formulation.
v. Alkaloid resin based and alkaloid salt-based prosome composition:
vi.
Example 1: Alkaloid resin based Prosome composition Weight percent Example 2: Alkaloid salt based Prosome composition Weight percent
Alkaloid resin 37% Alkaloid salt 37%
Permeation enhancement matrix composition Permeation enhancement matrix composition
lipid matrix 14% Lipid matrix 13.7%
Tween (80) 5 % Tween (80) 5.4%
Microcrystalline cellulose (MCC) 44% Microcrystalline cellulose (MCC) 43.7%
vii.

Prosome powder composition prepared by evaporating the solvent as per example 1 was subjected to stability study as follows:
The prosome powder was kept under accelerated stability condition of 40°C temperature & 75% Relative humidity for 6 months’ time period. Post this, sample was analyzed to measure the assay of alkaloid content by UV method and found to be 98.2% indicating good stability of prosome powder.
[042] In an exemplary embodiment of the invention the following provides the process of preparation:
[043] 1. Preparation of the Lipid Matrix and Active Ingredient:
a. The lipid matrix components are mixed in a specified ratio, typically with the total lipid content being between 10-25% of the total composition.
b. The active ingredient is added to the lipid matrix in amounts ranging up to 75% by weight of the total composition, depending on the specific active used and desired release profile.
[044] 2. Formation of the Non-Aqueous Slurry:
The lipid matrix and active ingredients are combined with the selected solvent to form a homogeneous slurry. The solvent is used in an amount sufficient to dissolve the lipid matrix and evenly distribute the active ingredient.
[045] 3. Rotary Evaporation:
The slurry is subjected to rotary evaporation, by evaporating the solvent from the mixture at any of the temperature ranging from ambient temperature of 25°C to the respective boiling point temperature of the selected solvent, depending on the sensitivity of active to thermal conditions. The pressure at which the evaporation takes place at a given temperature ranges from vacuum pressure of 16 mbar to atmospheric pressure depending on the solvent. Mild temperature options ensure that the active ingredient remains stable and avoids the use of high temperatures that could degrade temperature-sensitive compounds. The evaporation process results in a free-flowing granular prosome formulation.
Formulations are tabulated below w.r.t their free-flowing characteristics:
Example No Prosome Compressibility
Index CI (%) Hausner ratio (HR) Comments as per USP 1174
1 Alkaloid resin prosome 13.63 1.15 Good flow
2 Alkaloid salt prosome 13.95 1.16 Good flow

The flow property of the prosome formulation was evaluated using USP 1174 method. Study resulted in Hausner ratio (HR) and compressibility index (CI) values derived from the bulk and tapped density of prosome formulation. The resulted values indicated good powder flowability with compressibility index value of 13.63 and Hausner ratio of 1.15 for alkaloid resin and compressibility index value of 13.95 and Hausner ratio of 1.16 for alkaloid salt respectively.
As per USP 1174, particles having either Hausner ratio in the range of 1.12-1.18 or compressibility index in the range of 11-15, can be considered as “free flowing particles”.
[046] 4. Storage and Handling:
The prosomes are stored in a dry environment, dark room free from light, typically in a vacuum-sealed container, in low to ambient temperature condition to maintain stability. The formulation remains stable over extended periods under standard storage conditions.
[047] The free-flowing prosome formulation upon hydration leads to a formulation that shows enhanced permeability of the active in buccal model in comparison to the control active. Such instantaneous self-assembly of the active loaded liposome forms the desired particle size and contributes to enhanced permeation.
[048] In a specific embodiment of the invention the following gives the specific steps for preparation of composition:
Examples:
Example 1: Alkaloid Resin Prosome components
i. Alkaloid resin - 37% by weight.
ii. Lipid matrix - 14% by weight (comprising of saturated fatty acid at 9-90% and unsaturated fatty acid at less than 10% by weight)
iii. Surfactant (polysorbate 80) - 5% by weight.
iv. Filler (microcrystalline cellulose) - 44% by weight.
Process
[049] The ingredients are mixed to form a slurry with hexane. The slurry is subjected to evaporating the solvent from the mixture starting at a mild temperature at 25°C (at a vacuum pressure of 77 mbar) to a maximum moderate temperature of 55° C (at a vacuum pressure of 295 mbar).
Buccal permeability
Buccal permeability is analyzed using commercially available membrane called PermeaPad®. It consists of two cellulose membranes based on a novel biomimetic barrier unit with phospholipid bilayer for permeation screenings. The effective pore size of the buccal mucosa was in the same order of magnitude as other biological membranes.
[050] Buccal permeability of alkaloid from alkaloid resin and alkaloid resin prosomes.
[051] The permeability coefficient of alkaloid from alkaloid resin is 5.7± 0.25*10-6 cm/s, which is medium permeable.
[052] The permeability coefficient of alkaloids from alkaloid resin prosomes is 30 ± 0.36 *10-6 cm/s, which is highly permeable (Enhancement from medium to high).
[053] Outcome: Significant increase in permeability co-efficient (Papp factor) of alkaloid from prosomes when compared to alkaloid from alkaloid resin is established. Upon hydration, the prosomes form liposomes, demonstrating a significant increase in the permeability coefficient (Papp factor) to 30 ± 0.36 × 10?6 cm/s compared to the control.
Example 2: Alkaloid salt with alkaloid as an active ingredient.
Alkaloid Salt Prosome Formulation
i. Alkaloid salt – 37.2% by weight.
ii. Lipid matrix 13.7% by weight (comprising of saturated fatty acid at 9-90% and unsaturated fatty acid at less than 10% by weight).
iii. Filler (Microcrystalline cellulose) – 43.7% by weight.
iv. Surfactant (polysorbate) – 5.4% by weight.

Process:
The ingredients are mixed to form a slurry with hexane. The slurry is subjected to evaporating the solvent from the mixture starting at a mild temperature at 25°C (at a vacuum pressure of 77 mbar) to a maximum moderate temperature of 55° C ( at a vacuum pressure of 295 mbar).
Buccal permeability
Details of in-vitro permeability studies of prosome-based formulations are presented below:
[054] Buccal permeability of alkaloid from alkaloid salt and alkaloid salt prosomes.
[055] The permeability coefficient of alkaloid from alkaloid salt is 5.4±0.56*10-6 cm/s, which is medium permeable.
The permeability coefficient of alkaloids from alkaloid salt prosome is 25±0.29*10-6cm/s, which is highly permeable (Enhancement from medium to high).
[056] Outcome: Significant increase in permeability co-efficient (Papp factor) of alkaloid from prosomes when compared to alkaloid from alkaloid salt is established.
[057] These embodiments provide a comprehensive and versatile approach for enhancing the delivery of active ingredients, making the invention applicable to a wide range of therapeutic, nutraceutical, and consumer health products.
[058] In certain embodiments, the prosome formulations are formulated into an edible composition such as a pouch which is capable of retaining the suitable active in the oral cavity and providing enhanced permeation and fast absorption. To increase absorption, the active must be localized to the mucosal surface and ideally, a delivery system will release the active where it is absorbed.
[059] Prosome composition enhances the lipophilicity of the molecule and in turn enhances the permeability of the active and offers superior functional characteristics to the user when incorporated in various edible compositions such as pouches, snus, snuff, lozenges, film, gum, chewing gum, tablets and non-edible formulations such as patches, nasal, etc.
[060] The invention may be applied to various formulations and delivery methods, including:
Edible Products: Prosome formulations can be incorporated into products such as pouches, lozenges, films, gums, tablets, and strips for buccal or sublingual administration.
Non-Edible Products: The composition can also be used in topical formulations like patches or transdermal devices.
Custom Lipid Matrix Compositions: Different ratios of saturated and unsaturated fatty acids can be used to tailor the liposome formation properties and optimize permeation characteristics for specific actives.
Dual or Multiple Actives: The formulation can incorporate multiple active ingredients to achieve synergistic effects in enhancing permeability.
ADVANTAGE OF THE INVENTION
[061] Formation of prosomes formulation increases the permeation coefficient of any suitable active (both naturally/synthetically derived) through any suitable routes of administration. Matrix arising out of prosome mimics natural cell membranes, and they can better adhere to bio-membranes, and increase permeation at the site of the active delivery.
[062] The prosome formulation is a non-lyophilisation, non-dehydration approach to arrive at pro-liposome powder.
[063] The preparation method is a non-aqueous-based slurry approach employing suitable rotary evaporation (i.e. mild to moderate -thermal route) to arrive at a free-flowing prosome, powder and is a readily scalable method.
[064] In summary the following are the advantages of the present invention:
Non-Lyophilization and Non-Dehydration Approach: The method avoids the complex and energy-intensive processes typically used in traditional formulations.
Stability for Temperature-Sensitive Actives: The mild to moderate-temperature rotary evaporation process ensures that sensitive ingredients remain stable throughout preparation.
Scalability and Commercial Viability: The use of rotary evaporation enables large-scale production without compromising the quality of the formulation.
Improved Permeability: The prosome composition significantly increases the permeability of active ingredients across mucosal membranes compared to conventional formulations.
Dated this 16th Day of January 2025

Signature:
-Digitally Signed-
Name: Santosh Vikram Singh
IN PA 414
Agent For the Applicant
,CLAIMS:We claim:
1. A prosome composition, comprising:
(a) at least one, naturally or synthetically derived active ingredient;
(b) a lipid matrix comprising a combination of saturated and unsaturated fatty acid(s) or their ester(s);
(c) a non-aqueous solvent;
(d) an excipient;
wherein the prosome composition forms liposomes upon hydration, enhancing the permeation coefficient of at least one active ingredient.
2. The prosome composition as claimed in claim 1, wherein the active ingredient is at least one, naturally or synthetically derived alkaloid, alkaloid resin/polymer, alkaloid salt, vitamin, or a combination thereof, in an amount up to 75% by weight of the composition.
3. The prosome composition as claimed in claim 1, wherein the lipid matrix is selected from saturated and unsaturated fatty acids and combinations thereof, constituting 10–25% by weight of the composition.
4. The prosome composition as claimed in claim 1, wherein the non-aqueous solvent is selected from isopropyl alcohol, hexane, chloroform, ethyl acetate or a combination thereof.
5. The prosome composition as claimed in claim 1, wherein the excipient includes surfactants, fillers, and carriers.
6. The prosome composition as claimed in claim 1, wherein the surfactant in an amount of 5–10% by weight is polysorbate 80, the filler in an amount of 30–50% by weight is microcrystalline cellulose, and the carrier in an amount of 10–20% by weight is selected from sugar alcohol(s).
7. The prosome composition as claimed in claim 1, wherein upon hydration, the prosome formulation forms liposomes with enhanced permeation coefficient of at least one active ingredient.
8. The prosome composition as claimed in claim 1, wherein the composition is used in edible delivery formats such as a pouch, gums, tablet, lozenge, strip, film, or a combination thereof.
9. The prosome composition as claimed in claim 1, wherein the composition is used in non-edible delivery formats such as patch, nasal spray, or transdermal device(s).
10. A method for preparing a prosome composition, comprising:
(a) providing at least one active ingredient;
(b) providing a lipid matrix about 14% by weight of the composition comprising a combination of saturated and unsaturated fatty acids or their ester(s);
(c) providing a non-aqueous solvent;
(d) contacting the active ingredient with the lipid matrix and solvent to form a slurry;
(e) subjecting the slurry to rotary evaporation and evaporating solvent from the mixture at the temperature ranging from 25°C- 55°C and at a pressure ranging from vacuum pressure of 16 mbar to atmospheric pressure, to remove the solvent and obtain a free-flowing granular prosome formulation.
11. The process as claimed in claim 10, wherein the rotary evaporation process is carried out at a preferred temperature of about 40°C to preserve the stability of temperature-sensitive active ingredients.

Dated this 16th Day of January 2025
Signature:
-Digitally Signed-
Name: Santosh Vikram Singh
IN PA 414
Agent For the Applicant