DESC:
FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)

1. Title of the invention – MOUTH DISSOLVING FILM OF CURCUMIN AND PIPERINE
2. Applicant(s)
NAME: Avery Pharmaceutical Pvt Ltd
NATIONALITY: INDIAN
ADDRESS: Plot No- 12, 13, 14, Shubh Laxmi Industrial Estate, Opposite Eye Hospital, Sanand- Viramgam Highway, Village and Taluka – Sanand, District: Ahmedabad -382110, India.

3. PREAMBLE TO THE DESCRIPTION
The following specification describes the invention and the manner in which it is to be performed.

MOUTH DISSOLVING FILM OF CURCUMIN AND PIPERINE

FIELD OF THE INVENTION
The present invention is related to mouth dissolving film of Curcumin and Piperine. The present invention is particularly related to a mouth dissolving film of Curcumin and Piperine comprising curcumin, piperine, film forming polymer, plasticizer, and one or more inactive excipients and process for preparing the same.

BACKGROUND OF THE INVENTION
A sore throat is pain, scratchiness or irritation of the throat that often worsens when you swallow. The major cause of sore throats is a viral infection, like the common cold or flu. Sore throat symptoms typically go away in a few days. Symptoms of sore throat include pain or a scratchy sensation in the throat, pain that worsens with swallowing or talking, difficulty swallowing, swollen glands in your neck or jaw, swollen, red tonsils, and a hoarse or muffled voice.

There are some over-the-counter (OTC) medications that relieve throat pain which includes acetaminophen, Ibuprofen, Aspirin. There are some medications which work directly on the pain of a sore throat which includes throat sprays, throat lozenges, and cough syrups.

Medicinal plants have been used for traditional treatment for numerous human diseases since ages in many parts of the world. In rural areas of the developing countries, they are used as the primary source of medicine. About 80% of the people in developing countries uses traditional medicines for their health care. The frequent use of OTC products lead to development of resistance and they also have side effects. Hence, the search for alternative products continues, and natural phytochemicals isolated from plants used as traditional medicines are considered as a good alternative source.

Curcumin is a fat-soluble aromatic phyto-extract with orange-yellow pigment that has been firstly isolated from an Indian plant Turmeric (Curcuma longa L.) aromatic rhizome of the ginger family (Zingiberaceae). There are numerous in vitro, in vivo, and clinical studies that show it contained antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, and anti-viral infection.

Curcumin is extremely rich in antioxidants and it helps in managing various oxidative and inflammatory health concerns, metabolic problems, arthritis, anxiety and certain respiratory infections such as sore throat. Curcumin can also be beneficial in the treatment of inflammation caused by exercise and muscle soreness.

However, low oral bioavailability hampers its application as therapeutic agent. Pharmacokinetic properties of curcumin indicate that following oral administration, it is poorly absorbed and only traces of the compound appear in the blood, while most of it is excreted in the faeces. The transformation of curcumin into an unidentified compound during absorption and its glucuronidation in the liver are probably responsible for its low concentration in blood.

Piperine is the main constituent of Black pepper (Piper nigrum L) and long pepper (Piper longum L.) which have been in use as spices from ancient times throughout the world. Piperine has been reported to enhance the bioavailability of drugs by inhibition of glucuronidation in the liver and small intestine.

There are so many research articles which showed that combination of curcumin and piperine increases curcumin’s bioavailability significantly. Hence, there is need to provide a curcumin-piperine combination dosage form which will be different than conventional dosage forms for sore throat or as daily supplement for boosting immunity for prevention of many diseases.

Fast Drug Delivery Systems are rapidly gaining interest in the pharmaceutical industry. These systems either dissolve or disintegrate generally within a minute without needing water or chewing. These systems offer superior clinical profiles with potential oro-mucosal absorption thus increasing the drug bioavailability with respect to oral administration.

Mouth dissolving films are oral solid dosage form that disintegrate and dissolve within a minute when placed in mouth without taking water or chewing. Mouth dissolving film is the most advanced oral solid dosage form due to its flexibility and comfort in use. This dosage form allows the medication to bypass the first pass metabolism so bioavailability of medication may be improved .Mouth dissolving film has potential to improve onset of action lower the dosing. Mouth dissolving films have many advantages like no water required for consumption, accurate dosing as compare to liquid dosage forms, better patient compliance, direct drug delivery in systemic circulation, etc.

Though there are many conventional oral formulations of curcumin and/or curcumin-piperine. However, due to its weak solubility and bioavailability, it has limited potential as an oral medication. Hence, there is need to develop an oral formulation with newer technique which involves co-administration with piperine which will overcome the above stated drawbacks and also improves patient compliance.

Therefore, the inventors of the present invention have formulated a mouth dissolving film of curcumin in combination with piperine which will improve bioavailability of curcumin by direct delivery of curcumin in systemic circulation and avoiding first pass metabolism.

The objectives of the present invention are as described herein.

OBJECTIVE OF THE INVENTION
The main objective of the invention is to provide mouth dissolving film of curcumin and piperine.
The other main objective of the invention is to provide mouth dissolving film of curcumin and piperine which provides direct delivery of curcumin in systemic circulation.

Another objective of the invention is to provide mouth dissolving film of curcumin and piperine which has a better patient compliance.

Another objective of the invention is to provide mouth dissolving film of curcumin and piperine which provides faster absorption and higher bioavailability of the active constituents.

The other objective of the invention is to provide to mouth dissolving film of curcumin and piperine which does not need water for oral administration, yet dissolve / disperse/ disintegrate in the oral cavity.

SUMMARY OF THE INVENTION
The main aspect of the present invention is to provide mouth dissolving film of curcumin and piperine.

The other main aspect of the present invention is to provide mouth dissolving film of curcumin and piperine comprising curcumin, piperine, film forming polymer, plasticizer, and one or more inactive excipients.

Another aspect of the invention is to provide mouth dissolving film of curcumin and piperine and process of preparation of the same.

The details of one or more aspect of the invention are set forth in the description below. Other features, objects and advantages of the invention will be apparent from the description.

DESCRIPTION OF THE INVENTION
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are now described.

As used herein, the singular forms “a,” “an” and “the” specifically also encompass the plural forms of the terms to which they refer, unless the content clearly dictates otherwise.

As used herein, the term "formulation" or “composition”, unless otherwise defined refers to mouth dissolving film.

As mentioned herein the body of the invention the “Mouth dissolving film” is defined as oral solid dosage form that disintegrate and dissolve when placed in mouth without taking water or chewing.

The choice of particular types and amounts of excipients, and techniques for film preparation employed depends on the further properties of active ingredients and the excipients, e.g., film forming property, plasticity, solubility, particle size, compatibility, and density.

The films of the present invention may be prepared according to methods known in the art, including solvent casting method, semi-solid casting method, hot melt extrusion or rolling method and the type of excipients used will vary accordingly. It has been found that solvent casting method is particularly suitable for providing high film strength, low cracks films comprising relatively high concentrations on a scale suitable for commercial production.

As used herein the term “plasticizer” is defined as a substances or additives which increase the plasticity or fluidity of a material. Plasticizers are added to the polymers used as film forming agents in order to make the polymer pliable and soft, enhancing the flexibility and plasticity of the films.

As used herein the term “Polymer” is defined as a substances or additives which are combined to produce a final formulation is obviously very important and the distribution of components within the system can be critical to the desired functionality.

As used herein the term “cooling agent” is defined as agent used in a number of different formulations, such as hard confectionary products or oral gums, films, to provide a pleasant taste and a cooling sensation.

As used herein the term “liner” or “substrate” is food grade silicon polyester surface on which films can be casted and can easily be stripped from the substrate after drying.

The main embodiment of the present invention is mouth dissolving film of curcumin and piperine.

Another main embodiment of the present invention is mouth dissolving film of curcumin and piperine comprising curcumin, piperine, film forming polymer, plasticizer, and one or more inactive excipients.

As per one embodiment of the present invention, the said curcumin can be in any one form selected from curcumin, demethoxycurcumin, bisdemethoxycurcumin, cyclocurcumin 5’-methoxycurcumin, and dihydrocurcumin, its isomers, synthetic or semisynthetic derivatives, etc.

A per one embodiment of the present invention, the said curcumin can be used as extract or powder.

As per one embodiment, the said curcumin used in the present invention is curcumin extract 95%.

The curcumin extract used in the present invention is purchased from Rudra Actives, A-508, Star Heights, Opp. Shyam Farm, Nikol-Naroda Road, Behind Divine International School, Ahmedabad-382350, India.

As per one embodiment of the present invention, the said piperine can be in any one form selected from piperine, its isomers, synthetic or semisynthetic derivatives, etc.

A per one embodiment of the present invention, the said piperine can be used as extract or powder.

As per one embodiment, the said piperine used in the present invention is piperine extract 95%.

The piperine extract used in the present invention is purchased from Botanic healthcare Pvt Ltd, Plot No. 16/1/12 & 13, TSIIC IDA, Nacharam Uppal, Medchal-Malkajgiri, Dist Hyderabad, Telangana- 500076, India.

As per one embodiment of the present invention, the film forming polymer is selected from polyvinyl alcohol, hypromellose, sodium carboxy methyl cellulose, polyvinyl pyrrolidone, and hydroxy propyl cellulose, HPMC E50, HPMC E15, HPMC E3, HPMC E5, cellulose acetate, ethyl cellulose, gelatin, starch, pectin, chitosan, sodium alginate, polyethylene and Eudragit RL100.

As per preferred embodiment of the present invention, HPMC E5 is used as a film forming polymer.

As per one embodiment of the present invention, the plasticizer is selected from propylene glycol, ethanol, diethyl phthalate, dibutyl phthalate, glycerine, glycerol anhydrous, triethyl citrate, polyethylene glycol and polyethylene glycol 400.

As per preferred embodiment, plasticizer used in the present invention is glycerol anhydrous.

As per one embodiment of the present invention, the flavouring agent is selected from vanilla, strawberry, cocoa, coffee, chocolate, citrus, apple, pineapple, raspberry, Powder mango premium flavour, Orange Flavour, Mentholyptus supreme and cherry.

As per preferred embodiment, the present invention contains one or more flavouring agent, preferably combination of two flavouring agent.

As per another preferred embodiment of the present invention combination of Powder mango premium flavour and Mentholyptus Oil are used as flavouring agent.

As per one embodiment of the present invention, the use of Mentholyptus Oil also provides taste masking effect to the film.

As per one embodiment of the present invention, the sweetening agent is selected from sucrose, maltose, glucose, xylose, sucralose, aspartame, acesulfame-k, and stevioside.

As per preferred embodiment, sweetening agent used in the present invention is sucralose.

As per one embodiment of the present invention, the cooling agent is selected from monomethyl succinate, menthol, mannitol, Ecocool MP, WS3, WS23, and Utracoll II.

As per preferred embodiment, cooling agent used in the present invention is Ecocool MP.
As per one embodiment of the present invention, the composition comprising 30 to 70 % w/w curcumin extract, 1 to 20% w/w piperine extract, 1 to 50% w/w film forming polymer, 1 to 10% w/w plasticizer, 0.1 to 5% w/w sweetening agent, 0.1 to 10% w/w cooling agent and 1 to 20% w/w flavoring agent.

As per one embodiment of the present invention, the composition comprising 40 to 60 % w/w curcumin extract, 1 to 10% w/w piperine extract, 20 to 40% w/w film forming polymer, 1 to 5% w/w plasticizer, 0.1 to 3% w/w sweetening agent, 1 to 5% w/w cooling agent and 5 to 15% w/w flavoring agent.

As per one embodiment of the present invention, the solvent casting method is used for preparation of mouth dissolving film of curcumin and piperine. The solvent casting done by siliconized food-grade liner (substrate) having thickness of 15-200 micron, more preferable, 75 micron.

As per another main embodiment of the present invention, the process of preparation of mouth dissolving film of curcumin and piperine comprises the steps of,
a) Dissolving polymers in the water to make polymer solution;
b) Addition of plasticizer in the solution of step (a) and mixing to get a solution;
c) Dissolving curcumin, piperine, sweetening agent, cooling agent, flavouring agent in the water to get drug solution.
d) Mixing of solutions of step (b), and (c) to get uniform mixture;
e) Sifting of the mixture of step (d);
f) Casting of the mixture of step (e);
g) Cutting the films in to desired size;
h) Packing into suitable container.

As per one embodiment of the present invention, mouth dissolving film of curcumin and piperine provides thin film with higher bioavailability of curcumin and better patient compliance.

As per one more embodiment of the present invention, mouth dissolving film of curcumin and piperine is used in the treatment of sore throat or it is given as daily supplement to boost the immunity which helps to avoid many infections and diseases.

The invention is further illustrated by the following examples which are provided to be exemplary of the invention and do not limit the scope of the invention. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

EXAMPLE 1: TRIAL BATCHES FOR OPTIMIZATION OF A MOUTH
DISSOLVING FILM OF CURCUMIN AND PIPERINE
Sr. No. Ingredient Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7
Qty / Strip (%w/w)
1 Curcumin Extract 95% 60.000 56.25 52.326 50.000 50.000 50.000 50.000
2 Piperine Extract 95% 6.667 6.250 5.814 50.000 50.000 50.000 50.000
3 HPMC E3 28.000 - - - - - -
4 HPMC E5 - 26.25 - - - - -
5 HPMC E15 - - 26.744 27.778 27.778 27.778 27.778
6 PEG - 1.250 - - - - -
7 Glycerol Anhydrous 1.333 - 3.488 3.333 3.333 3.333 3.333
8 Sucralose 1.333 1.250 1.163 1.111 1.111 1.111 1.111
9 Ecocool MP 2.667 2.500 2.326 2.222 2.222 2.222 2.222
10 Powder mango premium - - 5.814 7.778 7.778 7.778 7.778
11 Orange Flavour - 6.250 - - - - -
12 Mentholyptus supreme - - 2.326 2.222 2.222 2.222 2.222
13 Purified Water QS QS QS QS QS QS QS
Total (%) 100.0 100.0 100.0 100.0 100.0 100.0 100.0
Table: 1 Formulation of a mouth dissolving film of curcumin and piperine
*Trial 4 to 7 are replicated trials with similar composition.

Results:
Evaluation Parameters Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Trial 6 Trial 7
Appearance Orange colour Orange colour Orange colour Orange colour Orange colour Orange colour Orange colour
Weight (mg) 75.2 80.5 86.3 90.3 90.40 87.54 84.81
Thickness (mm) 0.150-0.160 0.140 1.052 0.154 0.152 0.150 0.150
Weight variation (mg) - - - - - 83.66 to 87.72 83.61 to 86.01
Size (mm) 25 x 25 26 x 26 25 x 38 25 x 35 25 x 33 - -
Moisture Content (%) 7.5 10.5 10.5 11.0 9.5 2.37 2.28
% Assay Bulk Curcumin - - 85.61 - 113.18 - -
Piperine - - 98.04 - 113.49 - -
Finish Curcumin - - 102.04 - 98.07 96.28 94.55
Piperine - - 101.48 - 101.08 95.28 96.19
Disintegration time (sec) 5 min 216 321 385 225 97 105
Table 2: Results for trial batches for optimization of a mouth dissolving film of curcumin and piperine

As per the results, it was concluded that trial batch 6 & 7 are having good thickness and disintegration time. Hence, trial 6 & 7 are selected as an optimized batches. Trial 6 & 7 were replicated batches with similar composition.

EXAMPLE 2: OPTIMIZED COMPOSITION OF A MOUTH DISSOLVING FILM OF CURCUMIN AND PIPERINE

Sr. No. Ingredient Trial 6 Trial 7
Qty / Strip (%w/w)
Curcumin Extract 95% 50.000 50.000
2 Curcumin Extract 95% 50.000 50.000
3 HPMC E3 - -
4 HPMC E5 - -
5 HPMC E15 27.778 27.778
6 PEG - -
7 Glycerol Anhydrous 3.333 3.333
8 Sucralose 1.111 1.111
9 Ecocool MP 2.222 2.222
10 Powder mango premium 7.778 7.778
11 Orange Flavour - - -
12 Mentholyptus supreme 2.222 2.222 2.222
13 Purified Water QS QS QS
Total (%) 100.0 100.0 100.0
Table 3: Optimized Formulation of a mouth dissolving film of curcumin and piperine
Process of preparation:
a) Hypromellose was dissolved in the water to make polymer solution;
b) Glycerin was added in the solution of step (a) and mixed to get a solution;
c) Curcumin, Piperine, sucralose, Ecocool MP, Mango flavour, Mentholyptus Oil were dissolved in the water to get drug solution.
d) Solutions of step (b), and (c) were mixed to get uniform mixture;
e) The mixture of step (d) was sifted;
f) The mixture of step (e) was casted;
g) The films were cutted into desired size;
h) The final films were packed into suitable container.

EXAMPLE 3: EVALUATION OF A MOUTH DISSOLVING FILM OF CURCUMIN AND PIPERINE
The mouth dissolving films were evaluated for appearance, weight, thickness, weight variation, size, moisture content, disintegration time and assay.
Evaluation Parameters Trial 6 Trial 7
Appearance Orange colour Orange colour
Weight (mg) 87.54 84.81
Thickness (mm) 0.150 0.150
Weight variation (mg) 83.66 to 87.72 83.61 to 86.01
Size (mm) - -
Moisture Content (%) 2.37 2.28
% Assay Bulk Curcumin - -
Piperine - -
Finish Curcumin 96.28 94.55
Piperine 95.28 96.19
Disintegration time (sec) 97 105
Table 4: Results for optimized batches of a mouth dissolving film of curcumin and piperine

EXAMPLE 4: STABILITY TESTING OF MOUTH DISSOLVING FILM OF CURCUMIN AND PIPERINE
The mouth dissolving films were evaluated for their stability, at 25°C/60%RH, 30°C/75%RH and 40ºC/75%RH. The results shows that the product is stable up to 6 months.

Test Specification criteria Initial 3 Month 6 Month
Description Orange coloured thin film Orange coloured thin film Orange coloured thin film Orange coloured thin film
Average weight 90 mg ± 10% (81.0 mg to 99.0 mg) 87.54 mg 86.10 mg 90.10 mg
Moisture Content Not more than 15% 2.37 % 3.17 % 3.25 %
Disintegration Test Not more than 300 sec 97 Sec 128 Sec 135 Sec
Assay Piperine
(By HPLC) NLT 90.0% and NMT 125.0% of labelled amount of piperine 95.2 % 95.6 % 96.5 %
Total Curcuminodis (By HPLC) NLT 90.0% and NMT 125.0% of labelled amount of Total Curcuminodis 96.3 % 95.4 % 96.3 %
Microbial Analysis
Total Viable aerobic Count NMT 10000 cfu/gm 4000 cfu/gm NA NA
Total fungal count NMT 100 cfu/gm <10 cfu/gm NA NA
Bile tolerant gram negative bacteria NMT 100 cfu/gm Absent NA NA
Pseudomonas aeruginosa Should be absent/gm Absent NA NA
Escherichia Coli Should be absent/gm Absent NA NA
Salmonella Should be absent/ 10 gm Absent NA NA
S.aureus Should be absent/gm Absent NA NA
Table 5: Results for stability study of optimized batch trial 6 at 25°C/60%RH

Test Specification criteria Initial 3 Month 6 Month
Description Orange coloured thin film Orange coloured thin film Orange coloured thin film Orange coloured thin film
Average weight 90 mg ± 10% (81.0 mg to 99.0 mg) 87.54 mg 88.41 mg 90.07 mg
Moisture Content Not more than 15% 2.37 % 3.72 % 3.63 %
Disintegration Test Not more than 300 sec 97 Sec 113 Sec 115 Sec
Assay Piperine
(By HPLC) NLT 90.0% and NMT 125.0% of labelled amount of piperine 95.2 % 95.6 % 95.0 %
Total Curcuminodis (By HPLC) NLT 90.0% and NMT 125.0% of labelled amount of Total Curcuminodis 96.3 % 95.3 % 96.8 %
Microbial Analysis
Total Viable aerobic Count NMT 10000 cfu/gm 4000 cfu/gm NA NA
Total fungal count NMT 100 cfu/gm <10 cfu/gm NA NA
Bile tolerant gram negative bacteria NMT 100 cfu/gm Absent NA NA
Pseudomonas aeruginosa Should be absent/gm Absent NA NA
Escherichia Coli Should be absent/gm Absent NA NA
Salmonella Should be absent/ 10 gm Absent NA NA
S.aureus Should be absent/gm Absent NA NA
Table 6: Results for stability study of optimized batch trial 6 at 30°C/75%RH

Test Specification criteria Initial 3 Month 6 Month
Description Orange coloured thin film Orange coloured thin film Orange coloured thin film Orange coloured thin film
Average weight 90 mg ± 10% (81.0 mg to 99.0 mg) 84.81 mg 88.15 mg 88.12 mg
Moisture Content Not more than 15% 2.28 % 2.90 % 2.45 %
Disintegration Test Not more than 300 sec 105 Sec 113 Sec 124 Sec
Assay Piperine
(By HPLC) NLT 90.0% and NMT 125.0% of labelled amount of piperine 96.2 % 96.6 % 93.4 %
Total Curcuminodis (By HPLC) NLT 90.0% and NMT 125.0% of labelled amount of Total Curcuminodis 94.6 % 93.9 % 95.3 %
Microbial Analysis
Total Viable aerobic Count NMT 10000 cfu/gm 4000 cfu/gm NA 3150 cfu/gm
Total fungal count NMT 100 cfu/gm <10 cfu/gm NA <10 cfu/gm
Bile tolerant gram negative bacteria NMT 100 cfu/gm Absent NA NA
Pseudomonas aeruginosa Should be absent/gm Absent NA NA
Escherichia Coli Should be absent/gm Absent NA NA
Salmonella Should be absent/ 10 gm Absent NA NA
S.aureus Should be absent/gm Absent NA NA
Table 7: Results for stability study of optimized batch trial 6 at 40°C/75%RH

Test Specification criteria Initial 3 Month 6 Month
Description Orange coloured thin film Orange coloured thin film Orange coloured thin film Orange coloured thin film
Average weight 90 mg ± 10% (81.0 mg to 99.0 mg) 84.81 mg 88.11 mg 89.21 mg
Moisture Content Not more than 15% 2.28 % 3.22 % 3.15 %
Disintegration Test Not more than 300 sec 105 Sec 122 Sec 126 Sec
Assay Piperine
(By HPLC) NLT 90.0% and NMT 125.0% of labelled amount of piperine 96.2 % 96.1 % 94.1 %
Total Curcuminodis (By HPLC) NLT 90.0% and NMT 125.0% of labelled amount of Total Curcuminodis 94.6 % 95.4 % 97.2 %
Microbial Analysis
Total Viable aerobic Count NMT 10000 cfu/gm 4000 cfu/gm NA NA
Total fungal count NMT 100 cfu/gm <10 cfu/gm NA NA
Bile tolerant gram negative bacteria NMT 100 cfu/gm Absent NA NA
Pseudomonas aeruginosa Should be absent/gm Absent NA NA
Escherichia Coli Should be absent/gm Absent NA NA
Salmonella Should be absent/ 10 gm Absent NA NA
S.aureus Should be absent/gm Absent NA NA
Table 8: Results for stability study of optimized batch trial 7 at 25°C/60%RH

Test Specification criteria Initial 3 Month 6 Month
Description Orange coloured thin film Orange coloured thin film Orange coloured thin film Orange coloured thin film
Average weight 90 mg ± 10% (81.0 mg to 99.0 mg) 84.81 mg 88.85 mg 85.08 mg
Moisture Content Not more than 15% 2.28 % 3.94 % 3.45 %
Disintegration Test Not more than 300 sec 105 Sec 130 Sec 138 Sec
Assay Piperine
(By HPLC) NLT 90.0% and NMT 125.0% of labelled amount of piperine 96.2 % 95.2 % 95.5 %
Total Curcuminodis (By HPLC) NLT 90.0% and NMT 125.0% of labelled amount of Total Curcuminodis 94.6 % 95.3 % 96.7 %
Microbial Analysis
Total Viable aerobic Count NMT 10000 cfu/gm 4000 cfu/gm NA NA
Total fungal count NMT 100 cfu/gm <10 cfu/gm NA NA
Bile tolerant gram negative bacteria NMT 100 cfu/gm Absent NA NA
Pseudomonas aeruginosa Should be absent/gm Absent NA NA
Escherichia Coli Should be absent/gm Absent NA NA
Salmonella Should be absent/ 10 gm Absent NA NA
S.aureus Should be absent/gm Absent NA NA
Table 9: Results for stability study of optimized batch trial 7 at 30°C/75%RH

Test Specification criteria Initial 3 Month 6 Month
Description Orange coloured thin film Orange coloured thin film Orange coloured thin film Orange coloured thin film
Average weight 90 mg ± 10% (81.0 mg to 99.0 mg) 87.54 mg 88.29 mg 87.3 mg
Moisture Content Not more than 15% 2.37 % 2.81 % 2.61 %
Disintegration Test Not more than 300 sec 97 Sec 108 Sec 115 Sec
Assay Piperine
(By HPLC) NLT 90.0% and NMT 125.0% of labelled amount of piperine 95.2 % 95.7 % 94.9 %
Total Curcuminodis (By HPLC) NLT 90.0% and NMT 125.0% of labelled amount of Total Curcuminodis 96.3 % 92.8 % 94.5 %
Microbial Analysis
Total Viable aerobic Count NMT 10000 cfu/gm 4000 cfu/gm NA 3210 cfu/gm
Total fungal count NMT 100 cfu/gm <10 cfu/gm NA <10 cfu/gm
Bile tolerant gram negative bacteria NMT 100 cfu/gm Absent NA NA
Pseudomonas aeruginosa Should be absent/gm Absent NA NA
Escherichia Coli Should be absent/gm Absent NA NA
Salmonella Should be absent/ 10 gm Absent NA NA
S.aureus Should be absent/gm Absent NA NA
Table 10: Results for stability study of optimized batch trial 7 at 40°C/75%RH

From the results of stability data it is analysed that, the product is stable up to 6M at 25°C/60%RH, 30°C/75%RH and 40°C/75%RH.

From the all study data it can be concluded that the oral films of the present invention meet all criteria for a good film and remain stable for 6 months.
,CLAIMS:Claims,
We claim;
1. Mouth dissolving film of Curcumin and Piperine comprising curcumin extract, piperine extract, film forming polymer, plasticizer and one or more inactive excipients.
2. The mouth dissolving film of Curcumin and Piperine as claimed in claim 1, wherein the film forming polymer is selected from polyvinyl alcohol, hypromellose, sodium carboxy methyl cellulose, polyvinyl pyrrolidone, and hydroxy propyl cellulose, HPMC E50, HPMC E15, HPMC E3, HPMC E5, cellulose acetate, ethyl cellulose, gelatin, starch, pectin, chitosan, sodium alginate, polyethylene and Eudragit RL100.
3. The mouth dissolving film of Curcumin and Piperine as claimed in claim 1, wherein the plasticizer is selected from propylene glycol, ethanol, diethyl phthalate, dibutyl phthalate, glycerine, glycerol anhydrous, triethyl citrate and polyethylene glycol 400.
4. The mouth dissolving film of Curcumin and Piperine as claimed in claim 1, wherein the inactive excipients are selected from sweeting agent, cooling agent, two flavouring agents or combination thereof.
5. The mouth dissolving film of Curcumin and Piperine as claimed in claim 1, wherein the composition comprising 30 to 70 % w/w curcumin extract, 1 to 20% w/w piperine extract, 1 to 50% w/w film forming polymer, 1 to 10% w/w plasticizer, 0.1 to 5% w/w sweetening agent, 0.1 to 10% w/w cooling agent and 1 to 20% w/w flavoring agent.
6. The mouth dissolving film of Curcumin and Piperine as claimed in claim 1, wherein the composition comprising 40 to 60 % w/w curcumin extract, 1 to 10% w/w piperine extract, 20 to 40% w/w film forming polymer, 1 to 5% w/w plasticizer, 0.1 to 3% w/w sweetening agent, 1 to 5% w/w cooling agent and 5 to 15% w/w flavoring agent.
7. The mouth dissolving film of Curcumin and Piperine as claimed in claim 1, having thickness of 0.150 mm.
8. The mouth dissolving film of Curcumin and Piperine as claimed in claim 1, having disintegration time in the range of 95-390 sec.
9. The process for preparation of mouth dissolving film of Curcumin and Piperine as claimed in claim 1, comprises the steps of,
a) Dissolving polymers in the water to make polymer solution;
b) Addition of plasticizer in the solution of step (a) and mixing to get a solution;
c) Dissolving curcumin, piperine, sweetening agent, cooling agent, flavouring agent in the ater to get drug solution.
d) Mixing of solutions of step (b), and (c) to get uniform mixture;
e) Sifting of the mixture of step (d);
f) Casting of the mixture of step (e);
g) Cutting the films in to desired size;
h) Packing into suitable container.