Technical Field:
The present invention relates to a novel organogel composition for Orobuccal drug delivery. The novel organogel composition of the present invention comprises of one or more active ingredients.
Background and Prior Art:
Organogels are semi-solid systems, in which an organic liquid phase is immobilized by a three-dimensional network composed of self-assembled, interwoven gelator fibers. This three-dimensional network holds micro domains of the liquid in a non-flowing state mainly through surface tension. Some common examples of gelators include sterol, sorbitan monostearate, lecithin and cholesteryl anthraquinone derivatives. The gel is said to be a hydrogel or an organogel depending on the nature of the liquid component. A hydrogel has water as its liquid phase, while an organogel has an organic solvent as its liquid phase.
Organogels can be distinguished from hydrogels by their predominantly organic/non aqueous continuous phase and can then be further subdivided based on the nature of the gelling molecule: polymeric or low molecular weight (LMW) organogelators. Polymers immobilize the organic solvent by forming a network of either crosslinked or entangled chains for chemical and physical gels, respectively. The latter is possibly further stabilized by weak inter-chain interactions such as hydrogen bonding, van der Waals forces, and 7c-stacking. Likewise, the self-assembly of LMW organogelators depends on physical interactions for the formation of aggregates sufficiently long to overlap and induce solvent gelation. Depending on the kinetic properties of aggregates, an important distinction amongst LMW organogels is made between those composed of solid (or strong) versus fluid (or weak) fiber networks.
Despite the numerous trends in gelling processes and the impressive variety of gelators identified, it is difficult to predict the molecular structure of a potential gelator, as well as one cannot readily foresee preferentially-gelled solvents. Today

still, the discovery of gelators remains serendipitous and is usually followed by investigative screening of different solvent systems potentially compatible with gelation. Prediction of gelation potential of a given molecule might seem possible by investigation of its propensity towards chemical or physical inter-molecular interactions, however no generalizations are so far possible. Many factors such as steric effects, rigidity, and polarity can counter the molecule's aggregating tendency. Control over the gelation process as well as the conception of new gelling molecules remain important challenges to face in the quest of new organogelators.
Macroscopically, conventional organogels range from white opaque to translucent systems, depending on aggregate size and the consequent gel's ability to scatter incoming light. Sometimes, a same gel system will change upon small variations in composition.
In the pharmaceutical field, organogels can be used for drug and vaccine delivery via different administration routes. They have been studied for delivery of active via transdermal, ophthalmic and rectal. Organogels that have been studied for drug delivery include in-situ forming organogels from L-alanine derivatives, Eudragit gels, lecithin gels, microemulsion based gels (MBGs) and sorbitan monostearate gels and sorbitan monostearate gels.
Lecithin organogels have emerged as one of the most potential carrier systems. The organogel matrix mainly consists of a surfactant (lecithin) as gelator molecules, a nonpolar organic solvent as external or continuous phase, and a polar agent, usually water. Lecithin organogels have been used as carriers for hydrophilic and hydrophobic drug molecules.
Sorbitan monostearate (Span 60) and sorbitan monopalmitate (Span 40) have been found to gel a number of organic solvents at low concentrations. The use of a microemulsion or nanoemulsion gel as vehicle may enhance transdermal penetration

by various mechanism. Microemulsions induce a change in the thermodynamic activity of the drug they contain, modifying their partition coefficient and thus favour penetration of the stratum corneum.
Organogels based on other low molecular weight gelators have been investigated for transdermal delivery of drugs. A few polyethylene organogels are studied for pharmaceutical applications. Supramolecular organogels, such as eudragit organogels, in-situ forming organogel of L-alanine derivative and pluronic lecithin organogels are currently under research.
As far as drug delivery is concerned, the absence of aqueous phase is beneficial as the non-aqueous medium is less likely to support microbial growth. The non-aqueous medium of organogels also indicates their potential suitability as carriers for oil soluble drugs, whereas soft, semi-solid consistencies point to their use for application to the skin. Drug incorporation into the gels is known to alter the gel properties; such as viscosity and in some cases, drug incorporation even destroys the gel. Thorough characterization of the gel is necessary when drugs are dissolved or suspended in organogels.
Organogels, especially lecithin organogels are widely studied for transdermal drug delivery. Lecitihin organogel systems are described in US7776349 and US2009285869 for transdermal drug delivery. EP2500038 describes a pharmaceutical organogel composition containing a fatty acid ester and a glycerin fatty acid ester for transdermal drug delivery.
US5976547 and US2007292493 describe pluronic lecithin organogels for topical and transdermal application respectively.
The use of organogel products is increasing due to inherent long term stability owing to non aqueous medium. They are fhermoreversible and have the ability to

accommodate both hydrophilic and hydrophobic compounds within the gel structure. The gelators which compose the major skeleton of an organogel are generally amphiphilic substances.
Today, it is a challenge to develop organogel using the existing gamut of excipients. The inventors of the present invention have developed a novel organogel system suitable for orobuccal drug delivery using cellulose which readily gels in organic solvent. The present invention provides organogel composition comprising of one or more active ingredients suitable for orobuccal drug delivery.
Object of the Invention:
The object of the present invention is to provide an orally safe solvent based transparent novel organogel system suitable for orobuccal drug delivery.
Another object of the present invention is to provide an organogel system suitable for orobuccal drug delivery using cellulose which readily gels in organic solvent.
Another object of the present invention is to provide an organogel composition comprising of one or more active ingredients.
Summary of the Invention:
The present invention relates to a novel organogel system suitable for oral/orobuccal drug delivery containing solvent composition that is safe for orobuccal use in large quantities.
The present invention also relates to an organogel composition comprising one or more active ingredients.
Description of the Present Invention:
The inventors of the present invention provide a novel pharmaceutical organogel system suitable for oral/orobuccal drug delivery. The present organogel composition is

a relatively simple and easy to prepare organogel system that can incorporate a wide variety of pharmaceutical active ingredients. Owing to the properties of the novel organogel system, it can incorporate hydrophilic as well as hydrophobic active ingredients for oral/orobuccal drug delivery.
The novel organogel composition of the present invention fulfils the unmet need of a suitable pharmaceutical organogel system for oral/orobuccal drug delivery. The said organogel system comprises of pharmaceutically acceptable excipients which belong to GRAS (generally regarded as safe) category for oral/orobuccal drug delivery.
The organogel composition of the present invention comprises of an organogelator, organic solvent, preservative and optionally comprising of co-solvent. The said organogel composition can optionally comprise of pharmaceutically acceptable additives. The said organogel composition may comprise of one or more pharmaceutically active ingredients.
In one embodiment, the present invention provides a novel Organogel composition comprising active ingredient, organogelator, organic solvent, preservative and pharmaceutically acceptable excipients.
In one embodiment, the present invention provides the novel Organogel composition comprising active ingredient, organogelator, organic solvent, optionally co-solvent and pharmaceutically acceptable excipients.
In one embodiment, the present invention provides the novel Organogel composition comprising active ingredient, organogelator, organic solvent and pharmaceutically acceptable excipients.
In one embodiment, the present invention provides the novel Organogel composition comprising one or more active ingredients, organogelator, organic solvent, preservative and pharmaceutically acceptable excipients.

In one embodiment, the present invention provides the novel Organogel composition comprising one or more active ingredients, organogelator, organic solvent and pharmaceutically acceptable excipients.
In one embodiment, the present invention provides the novel Organogel composition comprising one ore more active ingredient, one or more organogelator, one or more organic solvent, one or more preservative and pharmaceutically acceptable excipients.
In one embodiment, the present invention provides the novel Organogel composition comprising hydrophilic active ingredient.
In one embodiment, the present invention provides the novel Organogel composition comprising hydrophobic active ingredient.
In one embodiment, the present invention provides the novel Organogel composition comprising combination of hydrophilic and hydrophobic active ingredient.
The novel organogel composition of the present invention is a clear, transparent gel having viscosity in the range of 30,000 to 50,000 cps and pH of 4-5.
The pharmaceutically active ingredient which can be incorporated in the organogel system of the present invention can be selected from group comprising of Antibacterials, Anaesthetics, Antiseptics and combinations thereof.
Antibacterials which may be used according to the present invention include but are not limited to Metronidazole, Ornidazole, Clindamycin, Azithromycin and mixtures thereof.
Anaesthetics which may be used according to the present invention include but are not limited to Lignocaine, Benzoic acid, Bupivacine, Cinchocaine, Articaine and mixtures thereof.

Antiseptics which may be used according to the present invention include but are not limited to Benzalkonium chloride, Cetyl pyridinium chloride, Choline salicylate, Tannic acid, Glycerin, Chlorhexidine gluconate and mixtures thereof.
In accordance with the present invention, organogel comprising of active ingredient and one or more of organogelator, co-solvents, preservatives, flavors, sweeteners, and taste-masking ingredients.
Organogelator which may be used according to present invention include but are not limited to Methyl cellulose, Ethyl cellulose, Hydroxy propyl cellulose, Hydroxy ethyl cellulose, Hydroxy propyl methyl cellulose, Sodium carboxy methyl cellulose and mixtures thereof.
Solvents which may be used according to present invention include but are not limited to Propylene glycol, Polyethylene glycol, Glycerin, Sorbitol, Ethanol and mixtures thereof.
Preservatives which may be used according to present invention include but are not limited to Methyl paraben, Ethyl paraben, Propyl paraben, Sodium benzoate, Benzoic acid, Sorbic acid, Potassium carbonate, Priopionic acid, methyl paraben, sodium benzoate and mixtures thereof.
Flavours which may be used according to present invention include but are not limited to Citrus flavours, Liquorice, Root bear, Raspberry, Vanilla, fruit & berry, butter scotch, apple, apricot, peach, wild cherry, walnut, chocolate and mixtures thereof.
Sweeteners which may be used according to present invention include but are not limited to Sucrose, Sucralose, Neotane, Aspartame, Saccharin sodium, Glycerine, Sorbitol, Mannitol, Xylitol and mixtures thereof.

Taste masking agents which may be used according to present invention include but are not limited to Sodium Chloride, Sodium acetate, Sodium gluconate and mixtures thereof.
In accordance with the present invention, the organogel composition contains 0.1% to 5% Active ingredient, 0.5% to 4% Organogelator, 0.1% - 98.09% Solvent, 1% to 70% Co-solvent, 0.1% to 5% Preservative, 0.1 to 3% Flavour, 6.1% to 5% Sweetner, and 0.1 % to 10% Taste masking agent.
Although the invention has been described with reference to specific embodiments, this description is not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternate embodiments of the invention, will become apparent to person skilled in the art upon reference to the description. It is therefore contemplated that such modification can be made without departing from the spirit or scope of the present invention as defined.
The invention is further exemplified with the following examples and is not intended to limit the scope of the invention.
Example 1

Sr. No. Ingredient % w/w
1. Metronidazole benzoate 1
2. Lignocaine hydrochloride 2
3. Chlorhexidine gluconate solution 0.2
4. Hydroxypropyl cellulose (HPC) 2
5. Polyethylene glycol 20
6. Propylene glycol 72.8
7. Methyl paraben 0.1
8. Propyl paraben 0.01

Manufacturing process
1. In a clean S.S. vessel, Propylene glycol was heated to 60°C.
2. Methyl paraben and Propyl paraben were added to step 1 and stirred for 5 minutes.
3. Metronidazole benzoate was dissolved in Polyethylene glycol under stirring and was added to step 2, stirred for 5 minutes, followed by addition of Lignocaine hydrochloride and stirred for 5 minutes.
4. Chlorhexidine gluconate solution was added to step 3 and stirred for 5 minutes.
5. Hydroxypropyl cellulose (HPC) was dispersed in step 4 and the dispersion thus formed was cooled to room temperature to form a gel.
Example 2

Sr. No. Ingredient % w/w
1. Metronidazole benzoate 0.75
2. Lignocaine 5
3. Hydroxypropyl cellulose (HPC) 2
4. Propylene glycol 92.09
5. Menthol 0.05
6. Methyl paraben 0.1
7. Propyl paraben 0.01
Manufacturing process
1. In a clean S.S. vessel, Menthol was dissolved in Propylene glycol and kept aside.
2. In another clean S.S. vessel, Propylene glycol was heated to 60°C.
3. Methyl paraben and Propyl paraben was added to step 2 and stirred for 5 minutes.
4. Metronidazole benzoate was added to step 3 with continuous stirring, followed by Lignocaine and the said solution was stirred for 5 minutes.
5. Hydroxypropyl cellulose (HPC) was dispersed in step 4 and the dispersion was cooled to room temperature to form a gel.

6. Solution from step 1 was added to gel from step 5 and stirred for 45 minutes.
Example 3

Sr. No. Ingredient % w/w
1. Ornidazole 1
2. Lignocaine 2
3. Hydroxypropyl cellulose (HPC) 2
4. Propylene glycol 94.2
5. Sodium saccharin 0.15
6. Menthol 0.1
5. Methyl paraben 0.5
6. Propyl paraben 0.05
Manufacturing process
1. In a clean S.S. vessel, Menthol was dissolved in Propylene glycol and kept aside.
2. In another clean S.S. vessel, Propylene glycol was heated to 60°C.
3. Methyl paraben and Propyl paraben were added to step 2 and stirred for 5 minutes.
4. Ornidazole was added to step 3 with continuous stirring, followed by Lignocaine and the said solution was stirred for 5 minutes.
5. Sodium saccharin was added to step 4 and stirred for 5 minutes.
6. Hydroxypropyl cellulose (HPC) was dispersed in step 5 and the dispersion was cooled to room temperature to form a gel.
7. Solution from step 1 was added to gel from step 7 and stirred for 45 minutes.
Example 4

Sr. No. Ingredient % w/w
1. Ornidazole 1
2. Hydroxypropyl cellulose (HPC) 2

3. Propylene glycol 76.13
4. Sorbitol 20
5. Menthol 0.1
6. Methyl paraben 0.7
7. Propyl paraben 0.07
Manufacturing process
1. In a clean S.S. vessel, Menthol was dissolved in Propylene glycol and kept aside.
2. In another clean S.S. vessel, Propylene glycol was heated to 60°C.
3. Methyl paraben and Propyl paraben were added to step 2 and stirred for 5 minutes.
4. Ornidazole was added to step 3 and stirred for 5 minutes.
5. Hydroxypropyl cellulose (HPC) was dispersed in step 4 and the dispersion was cooled to room temperature to form a gel.
6. Sorbitol was added to gel from step 5.
7. Solution from step 1 was added to gel from step 6 and stirred for 45 minutes.
Example 5

Sr. No. Ingredient % w/w
1. Metronidazole benzoate 2
2. Hydroxypropyl cellulose (HPC) 2
3. Propylene glycol 75.79
4. Glycerine 5
5. Sorbitol 15
6. Menthol 0.1
7. Methyl paraben 0.1
8. Propyl paraben 0.01
Manufacturing process
A
1. In a clean S.S. vessel, Menthol was dissolved in Propylene glycol and kept aside.

2. In another clean S.S. vessel, Propylene glycol was heated to 60°C.
3. Methyl paraben and Propyl paraben were added to step 2 and stirred for 5 minutes.
4. Metronidazole benzoate was added to step 3 and stirred for 5 minutes.
5. Hydroxypropyl cellulose (HPC) was dispersed in step 4 and cooled to room temperature to form a gel.
6. Sorbitol and Glycerin were added to gel from step 5.
7. Solution from step 1 was added to gel from step 6 and stirred for 45 minutes.
Stability Data of Example 1 :
Table 1.
Batch No :RMFD1
Storage Condition: 40° C ± 2° C / 75% ± 5% RH

Tests Specification Rexidin M Forte gel
Initial 1 month 2 Months 3 Months
Description Clear pale yellow coloured gel Complies Complies Complies Complies
Assay of
Metronidazole 95-105% 99.80% 99.30% 97.80% 96.10%
benzoate
Assay of
Lignocaine 95-105% 98.20% 97.50% 86.50% 97%
hydrochloride
Assay of
Chlorhexidine 95-105% 101.20% 98.60% 99.80% 96.10%
gluconate
pH Between
4-5.5 4.85 4.87 4.56 4.55

Remark: The data from table 1 shows that the product is stable at 40° C ± 2° C / 75% ± 5% RH for the period of 3 months.
contains 0.1% to 5% Active ingredient, 0.5% to 4% Organogelator, 0.1% - 98.09% Solvent, 1% to 70% Co-solvent, 0.1% to 5% Preservative, 0.1 to 3% Flavour, 0.1% to 5% Sweetner, and 0.1 % to 10% Taste masking agent.

We Claim:
1. A novel Organogel composition comprising 0.1% to 5% active ingredient, 0.5% to 4% organogelator, 0.1% - 98.09% organic solvent, 0.1% to 5% preservative and pharmaceutically acceptable excipients.
2. The novel Organogel composition of claim 1, wherein the organogelator is selected from the group consisting of Methyl cellulose, Ethyl cellulose, Hydroxy propyl cellulose, Hydroxy ethyl cellulose, Hydroxy propyl methyl cellulose, Sodium carboxy methyl cellulose, and mixtures thereof.
3. The novel Organogel composition of claim 1, wherein the organic solvent is selected from the group consisting of Propylene glycol, Polyethylene glycol, Glycerin, Sorbitol, Ethanol, and mixtures thereof.
4. The novel Organogel composition of claim 1, wherein the preservative is selected from the group consisting of Methyl paraben, Ethyl paraben, Propyl paraben, Sodium benzoate, Benzoic acid, Sorbic acid, Potassium carbonate, propionic acid, methyl paraben, sodium benzoate, and mixtures thereof.
5. The novel Organogel composition of claim 1 is without preservative.
6. The novel Organogel of claim 1, wherein the Organogel is in gel form.
7. The novel Organogel of claim 1, wherein the organogelator readily gels in organic solvent.
8. The novel Organogel composition of claim 1, wherein the active ingredient is
selected from the group consisting of Metronidazole, Ornidazole, Clindamycin,
Azithromycin, Lignocaine, Benzoic acid, Bupivacaine, Cinchocaine, Articaine,

Benzalkonium chloride, Cetyl pyridinium chloride, Choline salicylate, Tannic acid, Glycerin, Chlorhexidine gluconate and mixtures thereof.