Description:FORM 2
The Patent Act 1970
(39 of 1970)
&
The Patents Rules, 2003
(See section 10 and rule 13)

Complete Specification

Title: An orodispersible film formulation for prevention of nausea and a process of preparation thereof

Name of the Applicants:
1) AAVISHKAR ORAL STRIPS PRIVATE LIMITED, 109/3, IDA, Phase 2, Sector 2, Lane 6, Cherlapally, Hyderabad-500051, RR District, Telangana, India.
2) NUTRIZOE NUTRIIFOODS PRIVATE LIMITED, Unit No 611, Reliables Pride, Anand Nagar, Opp Heera Panna, Jogeshwari W, Mumbai – 400 102, Maharashtra, India.

Nationality: Indian(s).

The following specification particularly describes the invention and the manner in which it is performed.
Technical field
The present disclosure is in relation to thin film formulations for oral administration. More particularly, it provides an Orodispersible Film (ODF) formulation loaded with herbal extracts in general and ginger extract in particular along with a combination of different vitamins for prevention of nausea in subjects who are in need thereof.
Background
‘Nausea’ – is defined as an ‘unpleasant painless subjective feeling that one will imminently vomit’. While there are many reasons/ causes for nausea, but the most common cause of nausea is motion sickness. Additionally, nausea along with vomiting tendency is often seen in subjects undergoing chemotherapy (anti-cancer drugs cause chronic nausea) or radiation therapy. In short, nausea and vomiting are major complications in subjects undergoing cancer chemotherapy. Further, nausea and vomiting are also commonly evident during first and second trimesters of pregnancy. Few pregnant subjects’ exhibit chronic nausea and vomiting, leading to a medical condition termed as ‘Hyperemesis gravidarum’.
At present, there exist many drugs (anti-emetics – ondansetron and others) and its pharmaceutical formulations for prevention of nausea and vomiting. But, they all are associated with limitations and/or patient side-effects. For instance, some of the drugs employed for treating nausea had lead to teratogenic effects leading to birth defects in babies. Many traditional oral pharmaceutical formulations such as tablets, capsules and syrups of anti-emetics are available. But, they fail to gain patient compliance as the subjects/ patients are not in a condition to swallow (dysphagic) as they experience nausea and vomiting. Moreover, these formulations fail to offer necessary vitamins and minerals to impart desired nutritional benefits to the subjects in such conditions. Accordingly, there is a need for alternative active agents which are free of side effects, preferably herbal extracts, either alone or in combination with other vitamins and minerals with a strong potential to reduce nausea and/or vomiting. Additionally, there is also a need to design and develop alternate oral pharmaceutical formulations of herbal extracts alone or in combination with potential vitamins and minerals to help subjects in alleviating them from nausea and/or vomiting arising due to various causes. Altogether, there exists need for designing and developing a novel drug delivery system that are not cumbersome (swallowing and masticating) to consume orally in subjects experiencing nausea and/or vomiting. Thus, there is a need for fundamentally novel, safe and effective approach for preventing or treating nausea and/or vomiting arising due to various causes. The present disclosure is focused in this direction to offer a novel oral thin film formulation that rapidly disintegrates (orodispersible) for administration to subjects with nausea and/or vomiting.
Additionally, the information disclosed in this background section is only for enhancement of understanding of the general background of the disclosure and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.
Objectives
First and foremost objective of the present disclosure is to develop a Orodispersible Film (ODF) formulation loaded with ginger extract, vitamins in general and particularly vitamin combination comprising of vitamin C (ascorbic acid), Vitamin E (tocopherol), Vitamin B1 (Thiamine), Vitamin B2 (Riboflavin), Vitamin B9 (Folic acid), and Vitamin B12 (Cobalamin), and essential trace minerals namely zinc, and iodine.
Secondly, the disclosure is aimed at developing a process for preparation of Orodispersible Film (ODF) formulation loaded with ginger extract, vitamins in general and particularly vitamin combination comprising of vitamin C (ascorbic acid), Vitamin E (tocopherol), Vitamin B1 (Thiamine), Vitamin B2 (Riboflavin), Vitamin B9 (Folic acid), and Vitamin B12 (Cobalamin), and essential trace minerals namely zinc, and iodine.
Detailed Description
Before explaining any one embodiment of the present disclosure by way of drawings, experimentation, results, and pertinent procedures, it is to be understood that the disclosure is not limited in its application to the details as explained in below embodiments set forth in the following description or illustrated in the drawings, experimentation and/or results. The disclosure is further capable of other embodiments which can be practiced or carried out in various ways. As such, the language used herein is intended to be given the broadest possible scope and meaning; and the embodiments are meant to be exemplary and not exhaustive. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.
Definitions:
The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
‘Nutrients’ or ‘Micronutrients’ shall mean organic molecules that are essential in small quantities for normal functioning of metabolism in human body. Vitamin B complex is nothing but water soluble vitamins and are a supplement that delivers eight of the B vitamins namely B1 (Thiamine), B2 (Riboflavin), B3 (Niacin), B5 (Pantothenic acid), B6 (Pyridoxine), B7 (Biotin), B9 (Folate) and B12 (Cyanocobalamin). Vitamin D is a group of fat-soluble vitamins – most important in this group is Vitamin D3 (Cholecalciferol).
‘Orodispersible film(s)’ or ODF or ODFs shall mean thin sheets that disintegrate rapidly when placed/ administered to the tongue as they easily get hydrated due to the saliva in oral cavity.
“Film-forming substance” shall mean a substance capable of forming a cohesive, solid or gelatinous film or layer. The film or layer in particular can be formed by casting or otherwise applying a formulation containing the film-forming substance solved or dispersed in a solvent, and optionally further ingredients onto a surface. Preferably, the film-forming substance is a water-soluble polymer such as hydroxypropyl cellulose, pullulan and others that are obvious to a person skilled in the art.
“Plasticizer” shall mean a substance/ agent used to improve the flexibility of the orodispersible film. The plasticizer may be one selected from the group consisting of sorbitol, malitol, xylitol, glycerol, polyethylene glycol, propyleneglycol, hydrogenated starch syrup, starch syrup, triacetin, glycerol oleate, glycerol, sucrose fatty acid ester and double chain fatty acid. Preferably, the plasticizer used in the present invention is glycerol and sorbitol.
“Organoleptic agents” shall mean sweetening agents, coloring agents, and flavoring agents. No coloring agents were employed in the present disclosure.
“Sweetening agents” shall mean agents that impart more pleasant taste to the orodispersible film formulation. Generally, the sweetener may be at least one selected from the group consisting of sucrose, glucose, maltose, sucralose, oligosaccharides dextrin, alpha cyclodextrin, beta cyclodextrin, gamma cyclodextrin, methyl beta cyclodextrin, aspartame, cluster dextrin, invert sugar, fructose, lactose, galactose, starch syrup, sorbitol, malitol, xylitol, erythritol, hydrogenated starch syrup, mannitol, trehalose. Preferably, the orodispersible film of the present invention comprises sucralose, steviose and neohespiridine.
“Flavoring agents” shall mean any natural or artificial flavor or a combination thereof. The natural flavor may include aromatic plants, especially extracts and/oils obtained from leaves, flowers or fruits of such plants and can include spearmint oil, cinnamon oil, peppermint oil, lemon, oil, clove oil, bay oil, thyme oil, nutmeg oil, sage oil, almond oil etc. The artificial flavoring may include synthetic fruit flavors such as lemon, orange, grape, lime, strawberry, etc and other synthetic flavors such as vanilla, chocolate, coffee, cocoa, ginseng, citrus etc. Preferred flavoring agent employed in the present disclosure is peppermint oil.
“Acidic agent” shall mean a substance that serves to control taste together with the sweetener. Besides, it stimulates secretion of saliva in order to dissolve the orodispersible film. The acidic agent may be at least one selected from the group consisting of citric acid, malic acid, fumaric acid, tartaric acid, ascorbic acid, succinic acid, adipic acid, lactic acid. Preferable acidic agent is citric acid.
Additionally, the disclosure is further illustrated by the following examples, which are not to be construed in any way as imposing limitations upon the scope of the present invention. On the contrary, it is to be clearly understood that various other embodiments, modifications, and equivalents thereof, after reading the description herein in conjunction with the drawings and appended claims, may suggest themselves to those skilled in the art without departing from the spirit and scope of the presently disclosed and claimed invention.
Example 1: Method to prepare orodispersible films (ODFs) of vitamins
Table 1 provides the list of ingredients employed in preparing ODF formulation of the present invention. The method employed to fabricate the ODFs is called as industrial ‘solvent casting method’
Table 1: List of ingredients employed in the ODF
Sl.No. Name of the Ingredient Function Make
1. Gingerextract(GingeverTM) Active Botanica
2. Vitamin C(Ascorbic Acid) Active Reckon Organics
3. Zinc (Zinc Oxide) Active Zost
4. Vitamin E(Tocopherol Acetate) Active O BASF
5. Vitamin B1(Thiamine Hydrochloride) Active Prachi
6. Vitamin B2 (Riboflavin) Active Prachi
7. Vitamin B9(Folic Acid) Active Anuja Healthcare
8. Iodine (Potassium Iodide) Active Protochemicals
9. Vitamin B12 (Cyanocobalamin) Active Mahimapharma
10. Lecithin INS 322(ii) Emulsifier Amilife
11. Neusilin Adsorbent Fuji chemicals
12. Vinegar Bitter masker NA
13. Malic acid INS 296 Acidity regulator Daftodial
14. Coriander extract Taste Enhancer Synthite
15. Fennel seed extract Taste Enhancer Herbo Nutra
16. Natural Peppermint extract Taste Enhancer Konark
17. Pullulan INS 1204 Thickener Kumar Organics
18. Hydroxy Propyl Methyl Cellulose E5 INS 464 Thickener Dow
19. Calcium carboxy methyl cellulose Stabilizer Good will
20. Hydroxypropyl betadex Complexing agent Gangawal
21. Acryleze(Mixture of Methacrylic Acid Copolymer, Talc, Titanium Dioxide, Triethyl Citrate, Silica, Sodium Bicarbonate and Sodium Lauryl Sulphate) Bitter masker Colorcon
22. Menthol Masking agent Givaudan
23. Glyceryl Dibehenate Coating agent Galtefosse
24. Xanthan gum Thickener Deosen biochemicals
25. Potassium sorbate Preservative Shandong kundabiotechnolo
26. Sorbitol INS420 Stabilizer Rajaram
27. Glycerol INS 422 Humectant, Finar
28. Glycerol triacetate Wetting agent Alpha chemical
29. Lemon Flavor Flavor Robin
30. Ginger Flavor Flavor Givaudan
31. Natural Orange Flavor Flavor Keva
32. Neohesperidin Sweetener Boardas
33. Sucralose Sweetener Shandong
34. Malic Acid INS 296 Acidity Regulator Fuso chemicals
35. Honey Flavor Flavoring agent Keva
36. Erythritol INS 968 Sweetener Shandong

Sl.No. Name of the Ingredient F1 F2 F3
1. Gingerextract GingeverTM 0.667 0.667 0.667
2. Vitamin C (Ascorbic Acid) 10.416 10.416 10.416
3. Zinc (Zinc Oxide) 5.967 5.967 5.967
4. Vitamin E (Tocopherol Acetate) 3.667 3.667 3.667
5. Vitamin B2 (Riboflavin) 1.035 1.035 1.035
6. Vitamin B1 (Thiamine Hydrochloride) 0.767 0.767 0.767
7. Vitamin B9(Folic Acid) 0.354 0.354 0.354
8. Iodine (Potassium Iodide) 0.109 0.109 0.109
9. Vitamin B12 (Cyanocobalamin) 0.001 0.001 0.001
10. Lecithin INS 322(ii) 2.667 2.667 2.667
11. Neusilin 2.333 2.333 2.333
12. Vinegar 3.333 3.333 3.333
13. Malic Acid INS 296 0.667 0.667 0.667
14. Coriander extract 1.667 1.667 1.667
15. Fennel seed extract 1.667 1.667 1.667
16. Natural Peppermint extract 1.667 1.667 1.667
17. Pullulan INS 1204 13.402 17.402 17.402
18. Hydroxy Propyl Methyl Cellulose E 5 INS 464 14.382 10.382 10.382
19. Calcium carboxy methyl cellulose 3.333 3.333 3.333
20. Hydroxy Propyl Betadex 4.833 3.833 4.833
21. Acryleze 4.833 5.833 4.833
22. Menthol 4.833 4.833 4.833
23. Glyceryl dibehenate 4.333 4.333 4.333
24. Xanthan gum INS 415 0.500 0.500 0.500
25. Potassium sorbate INS 202 0.067 0.067 0.067
26. Sorbitol INS420 1.000 1.000 1.000
27. Glycerol INS 422 1.667 1.667 1.667
28. Glycerol triacetate 1.000 1.000 1.000
29. Lemon Flavor 0.400 0.300 0.400
30. Ginger Flavor 0.767 0.867 0.767
31. Orange Flavor 0.333 0.333 0.333
32. Neohesperidin 1.333 1.333 1.333
33. Sucralose 1.333 1.333 1.333
34. Malic Acid INS 296 2.667 2.667 2.667
35. Honey Flavor 1.333 1.333 1.333
36. Erythritol INS 968 0.667 0.667 0.667

It is pertinent to state that the concentration of the ingredients shown under Table 1 are the optimized concentrations arrived after a systematically designing the formulation experiments by Box-Behnken design. Different batches were tested and the batch that showed highly promising results are shown in example 1 and the same batch characterization studies are provided under the following examples. It is pertinent to state that negative data pertinent to different batches of the formulation is not shown here. Any variation in the concentration of the ingredients would not help in obtaining ODFs of vitamins which are acceptable to the subjects who are in need thereof. Some of the process parameters are tabulated below under Table 2.
Table 2: Critical process parameters to fabricate ODFs of vitamins
Process step Range
(Acceptance criteria) Justification
Deaeration Vacuum 600-700mmHg De aeration vacuum may impact on physical appearance finished product; vacuum should apply as specified.
Time 2 to 3Hours De aeration time may impact on physical appearance finished +product; time should as specify.
Layering and drying Thickness 700±10µ Within limit to avoid weight variation.
RPM 4.0-5.0 RPM more than the range will give wet layer and less will produce brittle layer.
Temperature 120±5ºC More temperature will give brittle and less temperature may produce wet layer.
Strip weight 300.0mg±5% Within limit to get correct assay value.
Slitting Tension 8-12Kg More tension will create tight winding leads to wet winding and less tension leads loose winding and difficult to packing.

Example 2: Physical methods for characterization of ODFs of vitamins
1.1 Physical examination
The fabricated Pullulan-based ODFs were physically examined with respect to the
appearance (using the naked eye), handling property, and texture.
1.2 Weight
The ODF samples were cut into a size of 32x 32 mm2 and weighed on an electronic balance (Mettler-Toledo, Mumbai, India). Average weight was considered as a mean weight Variation.
1.3 Thickness
The thickness of the film was measured using a screw gauge having an accuracy of 0.001
mm. Measurements were taken from the center and also from the four corners of the film having the size of 32x 32 mm2. The thickness measured is reported as mean (n=3) ± SD.
1.4 Disintegration time
Disintegration time of the ODFs was measured by a USP model disintegration apparatus, where in a film of 2x2cm2 was placed in the tubes dipped in phosphate buffer having pH of 6.8 (Simulated Salivary fluid). The time taken for the ODF to disintegrate completely was measured using a stop watch and the same experiment was repeated thrice and the mean value is reported.
1.5 Folding endurance
The fabricated ODF was folded repeatedly at a predetermined spot until it breaks. The number of times the film is folded without breaking is taken as the value of folding Endurance. The value was measured in triplicates.
1.6 Surface pH
The randomly selected ODF sample was moistened with distilled water (0.5 ml) and left for 2 min. The pH of the moistened film was measured using the pH meter (POLMON Instruments).In this method, the surface of the pH meter electrode is touched with the moistened surface of the film to measure the pH. Readings were taken in triplicates for each sample and the Average value of the readings is reported.
1.7 Karl Fischer titration (water content)
To determine the water content, Karl Fisher titration was performed using a DL37 Coulometrictitrator (ANALAB, Vadodara, Gujarat, India). Accuracy was checked using KF Reagent Pyridine Free (Merck). Methanol or anhydrous DMSO was used as solvents. One ODF sample (2x2 cm2) was added to about 5 ml methanol and the titration was continued Until it reaches an electrometric end point. The water content determination was performed in Triplicates corrected for solvent water content.

1.8 Microbial load
The ODF samples were tested for microbial burden (aerobic colony count, molds, yeasts, and coli forms) as per the
1.9 Assay and Dissolution
1.9.1 Assay of Gingerextract
1.9.1.1 Requirements
A) Apparatus Analytical balance, Spatulas (SS), Pipettes, Measuring cylinder (1000ml), Volumetric flasks (100ml,500ml), Sonicator, HPLC with UV detector
B) Chemicals and reagents
i) Water, monobasic potassium phosphate, Tetra butyl ammonium hydroxide, Methanol, Phosphoric acid, Ammonium hydroxide
1.9.1.2 Preparation of mobile phase: Take 900 ml of methanol and measure 100 ml of water in a beaker mix well, filter using 0.45µm Millipore membrane filter and sonicate for 10 minutes.
Diluent: 100 % HPLC grade Methanol
1.9.1.3 Preparation of standard solution:Weigh and transfer an accurately 80 mg of Ginger root extract working standard into 50 ml volumetric flask, add 25 ml of mobile phase, sonicate for 5 minutes and make up to volume with diluent and mix well.
1.9.1.4 Preparation of sample solution Weigh and transfer an accurately Multivitamin oral strips equivalent to standard (one strip) into 50 ml volumetric flask, add 25 ml of mobile Phase, sonicate for 5 minutes and make up to volume with diluent and mix well, and make up to volume with diluent mix well and filter through Whatman filter paper No.1

Chromatographic conditions
Column Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column

Column oven temp 30ºC ± 0.5°C

Flow Rate 1.0ml/ min

Volume of injection 20 µL
Wavelength 282nm
Runtime Time 20 minutes

Inject five standard injections and two sample injections, record the chromatograms and calculate the assay%.
1.9.2 Dissolution
1.9.2.1 Requirements:
A) Apparatus
i) Analytical balance, Spatulas (SS), Pipettes, Measuring cylinder (100Ml,1000ml), Volumetric flasks (100ml,500ml), Sonicator, Dissolution Apparatus USP II, HPLC with UV detector
B) Chemicals and reagents
i) Water, Methanol
1.9.2.2 Parameters:
Dissolution Apparatus: USP II (Paddle) (Samples are kept into mesh sinkers)
RPM: 100, Volume: 500 mL, Dissolution medium: Simulated saliva at pH 6.7 buffer, Time interval: 5, 10, 15, 20, 30 minutes.
1.9.2.3 HPLC instrument Parameters, Chromatographic conditions:
Instrument parameters:
Column Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column
Column oven temp 30ºC ± 0.5°C
Flow Rate 1.0 mL/min
Injection volume 20 µL
Wavelength 282nm
Run Time 20 minutes

1.9.2.4 Preparation of mobile phase: Take 900 ml of methanol and measure 100 ml of water in a beaker mix well, filter using 0.45µm Millipore membrane filter and sonicate for 10 minutes.
1.9.2.5 Preparation of standard solution: Weigh and transfer an accurately 75 mg of Ginger root extract working standard into 100 ml volumetric flask, add 5 ml of mobile phase, sonicate for 5 minutes and make up to volume with dissolution medium and mix well.
Pipette out 5 ml of resulting solution into 25 ml of volumetric flask, make up to volume with dissolution medium and mix well.
1.9.2.6 Sample Preparation: Transfer 500 mL of dissolution medium into each dissolution vessel and start the instrument.
After reaching the required temperature (37°C ± 0.5°C), transfer one strip into each dissolution vessel with sinkers and start the dissolution instrument.
Collect 10 ml of the dissolution sample after each specified time interval and replace the same volume in each vessel. Filter the samples solutions through 0.45µm filter and inject into the HPLC system.
1.9.3 Assay of Zinc (Zinc Oxide) Content by Titration
1.9.3.1 Requirements:
A) Apparatus
i) Analytical balance, Spatulas (SS), Pipettes, Measuring cylinder (1000ml), Volumetric flasks (100ml,500ml), Sonicator, Muffle furnace, Burette Stand, Burette, Conical flask.
B) Chemicals and reagents
i) Ammonium chloride, SulphuricAcid: 1 N, Methyl Orange TS, Sodium hydroxide
1.9.3.2 Preparation of sample solution: Weight approximately 0.300g of Sample which is freshly ignited in Muffle furnace for 30 minutes at 600 °C remove and cool it.
Analysis: Dissolve the ignited sample and 2.5 g of ammonium chloride in 50.0 ml of 1N Sulfuric acid against with the aid of gentle heat, if necessary. When solution is complete, add methyl orange TS. Titrate the excess sulfuric acid with 1 N Sodium hydroxide VS.
Each mL of 1 N Sulfuric acid is equivalent to 40.69 mg of Zinc Oxide
Note: Same method will be used for Dissolution.
1.9.4 Assay of Vitamin E (Tocopherol Acetate) by HPLC:
1.9.4.1 Requirements:
A) Apparatus
i) Analytical balance, Spatulas (SS) Pipettes, measuring cylinder (1000mL), Volumetric flasks (10mL,100mL,500mL), Sonicator
B) Chemicals and reagents
i) Acetonitrile, Methanol, Ethanol
1.9.4.2 Preparation of mobile phase: Measured 750 ml of acetonitrile and 250ml of Methanol mix well and filter through using 0.45µ Millipore membrane filter, sonicate for 10 minutes.
1.9.4.3 Preparation of standard solution: Weigh and transfer an accurately 20 mg of Vitamin E acetate working standard into 100 ml volumetric flask, add about 10 ml Ethanol mix well, sonicate for 1 minute and add 50 ml of water dissolve and make up to volume with Ethanol mix well. Pipette out 5 ml of resulting solution into 10 ml of volumetric flask, make up to volume with Ethanol.
1.9.4.4 Preparation of sample solution: Weighed and transfer an accuratelyNail the Nausea oral strips equivalent to standard into 100 ml volumetric flask, add about 50 ml of water mix well with cyclone mixer, sonicate for 30 minutes, mix well and make up to volume with Ethanol, mix well and filter throughWhatman filter paper No.1.Pipette out 5 ml of filtrate into 10 ml volumetric flask and made up to volume with diluent, mix well.

Chromatographic conditions
Column Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column
Column oven temp 30ºC ± 0.5°C

Flow Rate 1.0ml/ min

Volume of injection 20 µL
Wavelength 220nm
Runtime Time 30minutes

Inject five standard injections and two sample injections, record the chromatograms and calculate the assay%.

1.9.5 Dissolution:
1.9.5.1 Requirements:
A) Apparatus
i) Analytical balance, Spatulas (SS), Pipettes, Measuring cylinder (1000ml), Volumetric flasks (100ml,500ml), Dissolution Apparatus USPII, Sonicator
B) Chemicals and reagents
i) Acetonitrile, Methanol, Ethanol
1.9.5.2 Parameters:
Dissolution Apparatus: USP II (Paddle) (Samples are kept into mesh sinkers)
RPM: 100
Volume: 500 mL
Dissolution medium: Simulated saliva at pH 6.7 buffer
Time interval: 5, 10, 15, 20, 30 minutes.
1.9.5.3 HPLC instrument Parameters, Chromatographic conditions & Preparation of Mobile phase:
Instrument parameters:
Column Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column
Column oven temp 30ºC ± 0.5°C
Flow Rate 1.0 mL/min
Volume of injection 20 µL
Wavelength 220nm
Run Time 30 minutes

1.9.5.4 Preparation of mobile phase: Measured 750 ml of Acetonitrile and 250ml of Methanol mix well and filter through using 0.45µ Millipore membrane filter, sonicate for 10 minutes.
1.9.5.5 Preparation of standard solution: Weigh and transfer accurately 18 mg of Vitamin E acetate working standard into 100 ml volumetric flask, add about 10 ml Ethanol mix well, sonicate for 1 minute and add 50 ml of water dissolve and make up to volume with Ethanol mix well.
Pipette out 5 ml of resulting solution into 50 ml of volumetric flask, make up to
Volume with dissolution medium and mix well.
1.9.5.6 Sample Preparation:Transfer 500 mL of dissolution medium into each dissolution vessel and start the instrument.
After reaching the required temperature (37°C ± 0.5°C), transfer one strip into each dissolution vessel with sinkers and start the dissolution instrument.
Collect 10 ml of the dissolution sample after each specified time interval and replace the same volume in each vessel. Filter the samples solutions through 0.45µm filter and inject into the HPLC system.
1.9.6 Assay of Vitamin Vitamin B1 (Thiamine Hydrochloride)& Vitamin B2 (Riboflavin) by HPLC:
1.9.6.1 Requirements
A) Apparatus
i) Analytical balance, Spatulas (SS), Pipettes, Measuring cylinder (10mL,1000mL), Volumetric flasks (50mL,100mL), Dissolution Apparatus USP II, Sonicator
ii) HPLC with UV detector, ColumnBaker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column)

B) Chemicals and reagents
i) Acetic acid, Hexane Sulphonic acid, Sodium salt
ii) Sodium salt, Acetonitrile
1.9.6.2 Preparation of buffer:
a. Prepare 1 % acetic acid (solution A): Take 10 ml of acetic acid add into 1000 ml of water.
b. Preparation of 0.15% of Hexane sulphonic acid sodium salt: Weigh 1.5 g of Hexane Sulphonic acid sodium salt into 1% acetic acid solution (Solution B).
1.9.6.3 Preparation of mobile phase:Take 820 ml of buffer and 180 ml of Acetonitrile mix well and filtered by filtration until using 0.45µm Millipore membrane filtered and sonicate for 10 minutes.
1.9.6.4 Preparation of standard solution:Weigh and transfer accurately of 30 mgof Vitamin B1(Thiamine hydrochloride) and 40 mg of Vitamin B2 (Riboflavin)working standard into 100mlvolumetric flask, add50 ml of mobile phase, mix well and made up to volume with mobile phase, mix well.
1.9.6.5 Preparation of sample solution:Weigh and transfer an accurately of Multivitamin Oral Strips Equivalent standard weight into 100 ml volumetric flask, add 50ml of mobile phase dissolved by cyclone mixing, sonicate for 30 minutes and made up to volume with mobile phase mix well and Filtered throughWhatman filter paper No.1.

Chromatographic conditions
Column Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column
Column oven temp 25ºC ± 0.5°C
Flow Rate 1.0ml/ min
Volume of injection 20 µL
Wavelength 280nm
Runtime Time 15 minutes

Inject five standard injections and two sample injections, record the chromatograms and calculate the assay%.
1.9.7 Dissolution
1.9.7.1 Requirements
A) Apparatus
i) Analytical balance, Spatulas (SS), Pipettes, Measuring cylinder (500Ml,1000ml), Volumetric flasks (50ml,100ml), HPLC, Column (Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column, Sonicator
B) Chemicals and reagents
i) Acetic acid, Hexane Sulphonic acid, Sodium salt
ii) Sodium salt, Acetonitrile
1.9.7.2 Parameters:
Dissolution Apparatus: USP II (Paddle) (Samples are kept into mesh sinkers)
RPM: 100, Volume: 500 mL, Dissolution medium: Simulated saliva at pH 6.7 buffer, Time interval: 5, 10, 15, 20, 30 minutes.
1.9.7.3 HPLC instrument Parameters, Chromatographic conditions:
Instrument parameters:
Column Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column
Column oven temp 25ºC ± 0.5°C
Flow Rate 1.0 mL/min
Volume of injection 20 µL
Wavelength 280nm
Run Time 15 minutes
1.9.7.4 Preparation of buffer:
a) Prepare 1 % acetic acid (solution A): Take 10 ml of acetic acid add into 1000 ml of water.
b) Preparation of 0.15% of Hexane sulphonic acid sodium salt: Weigh 1.5 g of Hexane sulphonic acid sodium salt into 1% acetic acid solution (Solution B).
1.9.7.5 Preparation of mobile phase: Take 820 ml of buffer and 180 ml of Acetonitrile mix well and filtered by filtration unitl using 0.45µm Millipore membrane filtered and sonicate for 10 minutes.
1.9.7.6 Preparation of standard solution: Weigh and transfer accurately of 20 mg of Vitamin B1(Thiamine hydrochloride) and 25 mg of Vitamin B2 (Riboflavin)working standard into 100ml volumetric flask, add 5 ml of mobile phase, mix well and made up to volume with dissolution medium, mix well.
Transfer about 1 ml of the above solution into a 50 ml volumetric flask. Dilute to volume with dissolution medium.
1.9.7.7 Sample Preparation: Transfer 500 mL of dissolution medium into each dissolution vessel and start the instrument.
After reaching the required temperature (37°C ± 0.5°C), transfer one strip into each dissolution vessel with sinkers and start the dissolution instrument.
Collect 10 ml of the dissolution sample after each specified time interval and replace the same volume in thevessel. Filter the samples solutions through 0.45µm filter and inject into the HPLC system.

1.9.8 Assay of Vitamin B9(Folic Acid)by HPLC:
1.9.8.1 Requirements:
A) Apparatus
i) Analytical balance.
ii) Spatulas (SS)
iii) Pipettes.
iv) Measuring cylinder (1000ml)
v) Volumetric flasks (100ml,500ml)
vi) Sonicator
vii) HPLC with UV detector
viii) HPLC Column: Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column
B) Chemicals and reagents
1. Water.
2. monobasic potassium phosphate
3. Tetra butyl ammonium hydroxide
4. Methanol
5. Phosphoric acid
6. Ammonium hydroxide.

1.9.8.2 Preparation of Buffer Solution
i) Preparation of 0.5 M Tetra butyl ammonium hydrogen sulfate solution: Weigh 0.424 g of Tetra butyl ammonium hydrogen sulfate into 25 ml volumetric flask and 10 ml of water mix well and make up to the volume with water.
ii) Preparation of 3N Phosphoric acid solution:Take 98.0 g of Phosphoric acid into 1000 ml volumetric flask containing 700 ml of water and make up to volume with water mix well
iii) Preparation of 6N Ammonium hydroxide solution:Take 40 ml of 25% of Ammonium hydroxideinto 100 ml volumetric flask make up to volume with water.
1.9.8.3 Preparation of mobile phase: : Weigh and Transfer an accurately 2.0 g of monobasic potassium phosphate into a 1000ml of volumetric flask, and dissolve in 650ml of water, add 15 ml of solution of 0.5M Tetra butyl ammonium hydroxide ion methanol, add 7 ml of 3N Phosphoric acid, and 270 ml of methanol, cool to room temperature, adjust with 3N or 6 N Ammonium hydroxide to pH of 5.0 ± 0.05, make up to volume with water, mix well, filter using 0.45µm Millipore membrane filter and sonicate for 10 minutes.
1.9.8.4 Preparation Standard solution:Weigh and Transfer an accurately 10 mg of Folic acid standard into 50 ml volumetric flask, add 2 ml of 6 N Ammonium hydroxide solution, and make up to volume with mobile phase. Pipette out 1ml of resulting solution into 10 ml of volumetric flask, make up to volume with mobile phase.
1.9.8.5 Preparation of Sample solution: Weigh and Transferaccurately Multivitamin oral strips Equivalent to standard weight (ten strips) into 100 ml volumetric flask, add 4 ml of 6 N Ammonium hydroxide solution add 50 ml of mobile phase dissolved by cyclone mixing, sonicate for 30 minutes and made up to volume with mobile phase. Filtered through Whatman filter paper No.1 and pipette out 5 ml of filtrate into 10 ml of volumetric flask, make up to volume with mobile phase mix well.
Chromatographic conditions
Column Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column
Column oven temp 25ºC ± 0.5°C
Flow Rate 1.2ml/ min
Volume of injection 20 µL
Wavelength 280nm
Runtime Time 20minutes
Inject five standard injections and two sample injections, record the chromatograms and calculate the assay%.
1.9.9 Assay of Iodine (Potassium Iodide) By Titration:
1.9.9.1 Requirements:
A) Apparatus
i) Analytical balance.
ii) Spatulas (SS)
iii) Pipettes.
iv) Measuring cylinder (1000ml)
v) Volumetric flasks (100ml,500ml)
vi) Sonicator
vii) HPLC with UV detector
viii) HPLC Column: Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column
B) Chemicals and reagents
i) Potassium Iodate 0.05 M
ii) Amaranth TS
iii) Hydrochloric acid
iv) Sample Solution
1.9.9.2 Preparation of sample solution:Weight approximately 0.300g of Sample and dissolve in 10 mL of water and mix well.
Analysis: Add 35 mL of Hydrochloric acid to the sample of 10 mL into conical flask and titrate with 0.05 M Potassium iodate until the dark brown solution that is produced becomes pale brown. Add 2 to 3 drops of Amaranth TS and continue the titration slowly until the red color just changes to yellow color.Each mL of 0.05 M Potassium iodate is equivalent to 16.60 mg of Potassium Iodide.
Each mL of 0.05 M Potassium iodate is equivalent to 16.60 mg of Potassium Iodide.
Note: Same method will be used for Dissolution.
1.9.10 Assay of Vitamin B12(Cyanocobalamin) by HPLC:
1.9.10.1 Requirements:
A) Apparatus
i) Analytical balance.
ii) Spatulas (SS).
iii) Pipette.
iv) Measuring cylinder (1000ml).
v) Volumetric flasks (100ml,500ml).
vi) Sonicator.
vii) HPLC with UV Detector.
viii) HPLC Column: SpursilC18 with length 150mm, ID: 4.6mm and Particle size: 5µmequivalent.
B) Chemicals and reagents
i) Water.
ii) Monobasic potassium Phosphate
iii) Ortho phosphoric acid.
iv) Acetonitrile
1.9.10.2 Preparation of phosphate buffer solution: Weigh and Transfer an accurately 6.8 g of monobasic potassium Phosphate (KH2PO4) in 1000 ml of water, and adjust pH 3.7 ± 0.05 with dilute ortho phosphoric acid.
1.0
1.9.10.3 Preparation of mobile phase: Take 200 ml of Acetonitrile and 800 ml of phosphate buffer in a beaker and mix well, filter using 0.45µm Millipore membrane filter and sonicate for 10 minutes.
1.9.10.4 Preparation of standard solution: Weigh and transfer an accurately 11mg of Cyanocobalamin working standardinto 50ml volumetric flask and add 200 ml of water dissolve and make up to volume with water. Pipette out 1ml of resulting solution into 100 ml of volumetric flask, make up to volume with water.
1.9.10.5 Preparation of sample solution: Weighed and transfer an accurately of Multivitamin Oral strips Equivalent to standard weight into 100 ml volumetric flask and add 20 ml of water, sonicate for 30 minutes and cyclo mixed until the sample is complete dissolved, make up to volume with water after filtered through 0.45µm syringe filer.

Chromatographic conditions
Column Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column
Column oven temp 30ºC ± 0.5°C

Flow Rate 1.0ml/ min
Volume of injection 20 µL
Wavelength 254nm
Runtime Time 15 minutes

Inject five standard injections and two sample injections, record the chromatograms and calculate the assay%.

1.9.11 Dissolution
1.9.12 Requirements:
A) Apparatus
i) Analytical balance.
ii) Spatulas (SS).
iii) Pipette.
iv) Measuring cylinder (1000ml).
v) Volumetric flasks (100ml,500ml).
vi) Sonicator.
vii) HPLC with UV Detector.
viii) Dissolution Apparatus USP II
ix) HPLC Column: SpursilC18 with length 150mm, ID: 4.6mm and Particle size: 5µmequivalent.
B) Chemicals and reagents
i) Water.
ii) Monobasic potassium Phosphate
iii) Ortho phosphoric acid.
iv) Acetonitrile
1.9.12.1 Parameters:
Dissolution Apparatus: USP II (Paddle) (Samples are kept into mesh sinkers)
RPM: 100
Volume: 500 mL
Dissolution medium: Simulated saliva at pH 6.7 buffer
Time interval: 5, 10, 15, 20, 30 minutes.
1.9.12.2 HPLC instrument Parameters, Chromatographic conditions:
Instrument parameters:
Column Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column
Column oven temp 25ºC ± 0.5°C
Flow Rate 1.2 mL/min
Volume of injection 20 µL
Wavelength 280nm
Run Time 20 minutes

1.9.12.3 Preparation of Buffer Solutions:
i. Preparation of 0.5 M Tetra butyl ammonium hydrogen sulfate solution:
Weigh 0.424 g of Tetra butyl ammonium hydrogen sulfate into 25 ml volumetric flask and 10 ml of water mix well and make up to the volume with water.
ii. Preparation of 3N Phosphoric acid solution:
Take 98.0 g of Phosphoric acid into 1000 ml volumetric flask containing 700 ml of water and make up to volume with water mix well.
iii. Preparation of 6N Ammonium hydroxide solution:
Take 40 ml of 25% of Ammonium hydroxide into 100 ml volumetric flask make up to volume with water.
1.9.12.4 Preparation of mobile phase: Weigh and Transfer an accurately 2.0 g of monobasic potassium phosphate into a 1000ml of volumetric flask, and dissolve in 650ml of water, add 15 ml of solution of 0.5M Tetra butyl ammonium hydroxide ion methanol, add 7 ml of 3N Phosphoric acid, and 270 ml of methanol, cool to room temperature, adjust with 3N or 6 N Ammonium hydroxide to pH of 5.0 ± 0.05, make up to volume with water, mix well, filter using 0.45µm Millipore membrane filter and sonicate for 10 minutes.
1.9.12.5 Preparation Standard solution: Weigh and transferred accurately 10 mg of Folic acid standard into 100 ml volumetric flask, Add 2 ml of 6 N Ammonium hydroxide solution, and 5 ml of mobile phase. Mix well and make up to volume with Dissolution medium.
Pipette out 1ml of resulting solution into 100 ml of volumetric flask, make up to volume with dissolution medium.
1.9.12.6 Sample Preparation:
Transfer 500 mL of dissolution medium into each dissolution vessel and start the instrument.
After reaching the required temperature (37°C ± 0.5°C), transfer one strip into each dissolution vessel with sinkers and start the dissolution instrument.Collect 10 ml of the dissolution sample after each specified time interval and replace the same volume in each vessel. Filter the samples solutions through 0.45µm filter and inject into the HPLC system.

1.9.13 Vitamin C(Ascorbic Acid) by HPLC:
1.9.13.1 Requirements:
A) Apparatus
i) Analytical balance.
ii) Spatulas (SS).
iii) Pipette.
iv) Measuring cylinder (1000ml).
v) Volumetric flasks (100ml,500ml).
vi) Sonicator.
vii) HPLC with UV Detector.
viii) HPLC Column: SpursilC18 with length 150mm, ID: 4.6mm and Particle size: 5µmequivalent.
B) Chemicals and reagents
i) Water.
ii) Di sodium hydrogen phosphate anhydrous
iii) Ortho phosphoric acid.
iv) Acetonitrile
v) Methanol
1.9.13.2 Preparation of Phosphate Buffer: Weigh 7.80g of (Na2HPO4) disodium hydrogen phosphate anhydrous, and weigh 6.10 g of (KH2PO4) Potassium di hydrogen phosphate dissolve and make up to 1000 ml volume and adjust the pH to 3.0 by orthophosphoric acid.
1.9.13.3 Preparation of Mobile Phase: Measure the 500 ml of phosphate buffer to this add 500 ml of HPLC Grade Methanol and mix well and filter by filtration unit using 0.45µm Millipore membrane filter andsonicate for 10 minutes
1.9.13.4 Preparation Standard solution: Weigh and Transfer an accurately 50 mg of Ascorbic acid Working standard into 100ml volumetric flask, add 20 ml of Water dissolve and make up with mobile phase. Pipette out 1ml of resulting solution into 10 ml volumetric flask make up to volume with mobile phase and mix well.
1.9.13.5 Preparation of Sample solution: Weighed and transfer an accuratelyof Multivitamin Oral Strips Equivalent to standard (two strips) weight into 100 ml volumetric flask, add 20 ml of water dissolved by cyclone mixing, sonicate for 30 minutes and made up to volume with mobile phase again sonicate for 2 minutes and filtered through 0.45µm syringe filter. Pipette out 1 ml of filtrate into 10 ml volumetric flask made up to volume with mobile phase and mix well.

Chromatographic conditions
Column Baker bond (C18, 250mm x 4.6mm; 5µm) or Equivalent column
Column oven temp 30ºC ± 0.5°C

Flow Rate 1.0ml/ min
Volume of injection 20 µL
Wavelength 220nm
Runtime Time 10 minutes

Inject five standard injections and two sample injections, record the chromatograms and calculate the assay%.
4. In-Process Specification for slurry:
S. No. Test Specification
1. Description Yellowcolored, viscousslurry
2. Identification (By HPLC)
a) Gingerextract GingeverTM The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
b) Vitamin C (Ascorbic Acid) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
c) Zinc (Zinc Oxide) The Sample solution changes from pale pink color to colorless.
d) Vitamin E (Tocopherol Acetate) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
e) Vitamin B12 (Cyanocobalamin) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
f) Vitamin B2 (Riboflavin) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
g) Vitamin B9 (Folic Acid) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
h) Iodine (Potassium Iodide) The Sample solution changes from pale pink color to colorless.
i) Vitamin B1 (Thiamine Hydrochloride) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
6. Assay: 620 mg of slurry contains
a) GingerextractGingeverTM80 mg Between 90.0 % to 110.0 % of the label claim
b) Vitamin C (Ascorbic acid) 25 mg Not less than 90.0 % of the label claim
c) Zinc (Zinc Oxide) 1.75 mg Between 90.0 % to 110.0 % of the label claim
d) Vitamin E (Tocopherol acetate)10 mg Not less than 90.0 % of the label claim
e) Vitamin B12 (Cyanocobalamin) 2.2 mcg Not less than 90.0 % of the label claim
f) Vitamin B2 (Riboflavin) 2.7 mg Not less than 90.0 % of the label claim
g) Vitamin B9 (Folic Acid) 500 mcg Not less than 90.0 % of the label claim
h) Iodine (Potassium Iodide) 250 mcg Not less than 90.0 % of the label claim
i) Vitamin B1 (Thiamine HCl) 2 mg Not less than 90.0 % of the label claim

5. In-Process Product Specification:
S. No. Test Specification
1. Description Yellow colored square shaped dried oral strips.
2. Identification (By HPLC)
a) Gingerextract GingeverTM The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
b) Vitamin C (Ascorbic Acid) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
c) Zinc (Zinc oxide) The Sample solution changes from pale pink color to colorless.
d) Vitamin E (Tocopherol Acetate) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
e) Vitamin B12 (Cyanocobalamin) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
f) Vitamin B2 (Riboflavin) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
g) Vitamin B9 (Folic Acid) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
h) Iodine (Potassium Iodide) The Sample solution changes from pale pink color to colorless.
i) Vitamin B1 (Thiamine Hydrochloride) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
3. Average strip weight (mg) 300.0 mg ± 5%(Between 285.0- 315.0)
4. Moisture Content Between 3.0 to 8.0 % w/w
5. Disintegration time Not more than 60 seconds
6. Assay: Each strip contains
a) Ginger extract(GingeverTM)80 mg Between 90.0 % to 110.0 % of the label claim
b) Vitamin C(Ascorbic acid) 25 mg Not less than 90.0 % of the label claim
c) Zinc (Zinc Oxide) 1.75 mg Between 90.0 % to 110.0 % of the label claim
d) Vitamin E (Tocopherol acetate)10 mg Not less than 90.0 % of the label claim
e) Vitamin B12 (Cyanocobalamin) 2.2 mcg Not less than 90.0 % of the label claim
f) Vitamin B2 (Riboflavin) 2.7 mg Not less than 90.0 % of the label claim
g) Vitamin B9 (Folic Acid) 500 mcg Not less than 90.0 % of the label claim
h) Iodine(Potassium Iodide) 250 mcg Not less than 90.0 % of the label claim
i) Vitamin B1 (Thiamine HCl) 2 mg Not less than 90.0 % of the label claim

6. Finished Product Specification
S. No. Test Specification
1. Description Yellowcolored,squareshaped dried oral strips.
2. Identification (By HPLC)
a) Gingerextract (GingeverTM) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
b) Vitamin C (Ascorbic Acid) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
c) Zinc (Zinc Oxide) The Sample solution changes from pale pink color to colorless.
d) Vitamin E (Tocopherol acetate) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
e) Vitamin B12 (Cyanocobalamin) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
f) Vitamin B2 (Riboflavin) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
g) Vitamin B9 (Folic Acid) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
h) Iodine (Potassium Iodide) The Sample solution changes from pale pink color to colorless.
i) Vitamin B1 (Thiamine HCl) The retention time of the peak in the test solution corresponds to the chromatogram of the standard solution as obtained in the assay.
3. Average strip weight (mg) 300.0 mg ± 5%(Between 285.0- 315.0)
4. Moisture Content Between 3.0 to 8.0 % w/w
5. Disintegration time Not more than 60 seconds
6. Assay: Each strip contains
a) Gingerextract (GingeverTM)80 mg Between 90.0 % to 110.0 % of the label claim
b) Vitamin C (Ascorbic acid) 25 mg Not less than 90.0 % of the label claim
c) Zinc(Zinc Oxide) 1.75 mg Between 90.0 % to 110.0 % of the label claim
d) Vitamin E (Tocopherol acetate)10 mg Not less than 90.0 % of the label claim
e) Vitamin B12 (Cyanocobalamin) 2.2 mcg Not less than 90.0 % of the label claim
f) Vitamin B2 (Riboflavin) 2.7 mg Not less than 90.0 % of the label claim
g) Vitamin B9 (Folic Acid) 500 mcg Not less than 90.0 % of the label claim
h) Iodine (Potassium Iodide) 250 mcg Not less than 90.0 % of the label claim
i) Vitamin B1 (Thiamine HCl) 2 mg Not less than 90.0 % of the label claim
7. Heavy Metals
Lead (Pb) Not more than 3 ppm
Cadmium (Cd) Not more than 1 ppm
Arsenic (Ar) Not more than 1 ppm
Mercury (Hg) Not more than 0.1ppm
8. Pesticides Should be free from Specified Pesticides
9. Microbial tests
Total aerobic microbial count Not more than 1000 cfu/g
Total yeast and molds count Not more than 100 cfu/g

Pathogens
Escherichia coli Should be absent / g
Salmonella Should be absent / 10 g
Pseudomonas aeruginosa Should be absent / g

Staphylococcus aureus Should be absent / g

 
, Claims:1) An orodispersible film formulation for preventing nausea and/or vomiting, comprising of vitamin C (ascorbic acid), Vitamin E (tocopherol), Vitamin B1 (Thiamine), Vitamin B2 (Riboflavin), Vitamin B9 (Folic acid), and Vitamin B12 (Cobalamin), and essential trace minerals namely zinc, iodine and pharmaceutically acceptable excipients.
2) A process for preparing an orodispersible film formulation as claimed in claim 1, for preventing nausea and/or vomiting, comprising steps of:
a) dissolving zinc oxide, vitamin c, vitamin B2, vitamin B9, Iodine, and vitamin B12 to obtain a solution;
b) dissolving extracts of coriander extract, fennel seed extract, natural peppermint extract, potassium sorbate, neohesperidin, erythritol, malic acid, calcium carboxy methyl cellulose, lecithin, sorbitol, glycerol and glycerol triacetate to obtain second solution;
c) dissolving hydroxypropyl betadex, vitamin B1, glyceryl dibehenate, acryleze, menthol to obtain third solution;
d) dissolving neusilin and vitamin E to obtain fourth solution;
e) dissolving ginger extract in purified water along with vinegar, sucralose, malic acid, lemon flavor, ginger flavor, orange flavor and honey flavor to obtain fifth solution;
f) dissolving xanthan gum, HPMC, pullulan and purified water to obtain sixth solution;
g) all the solutions are mixed under continuous stirring in a tanker and casted on a solvent casting machine to obtain orodispersible film of predetermined size; and
h) processing parameters are as per the details mentioned in complete specification or detailed description.