FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
COMPLETE SPECIFICATION
(See Section 10; Rule 13)
1. NOVEL PHARMACEUTICAL DOSAGES FORM AND A PROCESS FOR MANUFACTURING THE SAME
2, ANKUR DRUGS AND PliARMA LTD, C- 306, CRYSTAL PLAZA, ANDHERI LINK ROAD, ANDHERI (W), MUMBAI - 400 053, MAHARASHTRA, INDIA, AN INDIAN COMPANY.
The following specification particularly describes the nature of the invention and the manner in which it is to be performed.

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FIELD OF INVENTION
The present invention relates to the field of a novel pharmaceutical oral dosages form of easy and rapid dissolution and of bitter taste masking in the form of stripes or thin films and a process for their preparations.
BACKGROUND / PRIOR ART
Most of the times it is very much inconvenient to take oral dosage form of bitter taste due to bitterness of the drugs. In order to overcome this sorts of problems while taking oral formulations containing bitter drugs, conventional approach of masking the tablet is adopted. A number of prior arts use to discuss such technical problems and find solution to this effect. US2005079213 discloses a solid oral dosage composition of cefuroxime axetil comprising a tablet inside a capsule, the capsule serving to mask the bitter taste of the drug upon oral administration. This tablet-in-a-capsule format is bioequivalent to the commercial film-coated tablet. WO0243707 finds an oral pharmaceutical composition of Cefuroxime Axetil, in tablet form, where the Cefuroxime Axetil is contained in the tablet core, coated with double layered film coat. The first film coat serves to mask the bitter taste of Cefuroxime Axetil and second film coat serves delay the rupture time beyond 40 seconds. W09312771 states a prolamine fractions of grain proteins, applied in weight rations of 5 to 100 % relative to the active agent being coated, effectively prevent die partitioning of water-soluble or water-insoluble drugs at neutral pH's in the mouth and thereby mask the taste of orally-administered drugs, which normally have a bitter taste, without sacrificing bioavailability. Zein, gliadin or a mixture thereof, particularly in combination with between 2.5 and 15 % of water-insoluble vegetable source oil or wax capable of plasticizing the prolamine fraction, when applied to particles, granules, tablets or other forms of drugs or nutritionals, to an effective thickness of about 1 to about 35 micrometers, in order to encapsulate and prevent release of an orally-administered pharmaceutical or nutritional in a suspension or chewable dosage form until such medicament reaches the stomach. *JUS4897270 discloses a pharmaceutical tablet which comprises a tablet core containing the antibiotic cefuroxime axetil and a film coat which serves to mask the bitter taste of the cefuroxime axetil upon oral administration. It has been found that conventional film-coated
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tablets reduce the bioavailability of cefuroxime axetil and the invention overcomes this by control of the film coat rupture time and use of a tablet core, which disintegrates immediately following rupture of the film coat.
The solution for masking of bitter drugs also appears in the way of a cover made of rice starch. Thin wafers of boiled rice mashie are made and the bitter drugs with its formulation is enclosed in between and becomes easy to administer. However, the masked tablet dosage gets dissolved in the digestive system and takes time for release of the drug. This approach some time fails to deliver the drug immediately whenever required. Administration of such masked tablets especially becomes inconvenient in case of children who cannot easily swallow the tablet Encountered with such shortcomings a novel dosage form in form of thin film or strip with accuracy of dosing is disclosed which is made of bitter tasted drugs instead of a masked tablet type (inconvenient to take from many aspects). In order to avoid the bitter taste of the drug in the dosage form sweeteners like maltodextrin, sucralose, sorbitol and the like are added during formulation of the strip or thin film along with flavours and colours. This dosage form works wonderfully being easily and rapidly dissolvable, easy to administer and gives fast relief to patients. Again by this dosage form a very accutate dosing required is attained immediately. For attaining such dosage form, a very specific manufacturing process employing a specially designed apparatus is utilised.
OBJECTIVE OF THE INVENTION
The main objective of the invention is formation of a pharmaceutical dosage form in the
form of a thin film / strip of drugs tasting bitter.
Another objective of the invention is formation of the dosage form to suppress the bitter
taste of the drug and availing easy dissolution in the mouth.
Further more objective of the invention is to achieve a pharmaceutical dosage form that
finds easy administration, very fast acting and easy acceptability in children.
One further more objective of the invention is to devise a process for manufacturing the
dosage form.
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SUMMARY OF THE INVENTION
The present invention discloses a novel pharmaceutical oral dosage form in form of thin strip / film employing various drugs tasting bitter. Other pharmaceutical adjuvants to improve the properties of the film / strip is disclosed including sweeteners and flavours to suppress the bitterness of the drugs carrying bitter taste.
The very delicate dosage form requires special provision for manufacturing via specially designed apparatus and that is adopted in order to carry out the invention.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a novel pharmaceutical oral dosage form of easy and rapid dissolution and of bitter taste masking in the form of stripes or thin films and a process for their preparation. The pharmaceutical dosage form comprises different components in their respective proportions to add the properties to the dosage as desired to find out a technical solutions to the existing problems. The active ingredients utilized for the invention are generally bitter in taste. The applicant has come out with s solution of masking the bitter taste of the active ingredients as well as providing easy dissolution and rapid availability of the active ingredients in the dosage form. Conventional ingredients like sweeteners, plasticizers, cellulose base, flavours and colours are provided in the dosage form. In a preferred embodiment, of the present invention the pharmaceutically active substance i.e. the drug is present in an effective amount as per the dosage form recommended. Once the oral strip or thin film is formed it works with accuracy of dosing required. In another embodiment, of the present invention, an accurate and sequential process to obtain the end product is devised controlling various parameters involved during formation of the oral strip or thin film.
Yet, in another embodiment, of the invention formation of thin film or strip with accurate dosing is covered which is a very critical task. An apparatus/ machine of very high accuracy and precision is implemented during the process operated.
The active pharmaceutical ingredients i.e. the drug that taste bitter are exploited for the
p present invention. In one operation only one drug is incorporated into the composition in an
effective amount as per dosage strength. The following drugsdiphenhydramine
hydrochloride, phentanyl, dextromethorphan hydrobromide, amlodipine besylate,

domperidone, diclofenac sodium, risperidone, tolterodine tartarate, loperamide
hydrochloride, cetrizine dihydro chloride, Zolpidem taratarate, olanzapene, fluoxetine
hydrochloride, montelukast sodium, atorvastatin calcium, isosorbide mononitrate, enalaptil
maleate, piroxicam, alprazolam alone form the basis of dosage form.
Since most of the above disclosed drugs taste bitter putting them as such into the
strip/thin film serves no purpose at all. To suppress the bitterness of the drugs sweetness
are added in quantitative amount. The sweetness like maltodextrin, sucralose, sorbitol or
mixture thereof in required quantity can be incorporated alone or in combination with.
Other important component of the formulation is cellulose, which is used as base
material. The very specific types of base materials are hypromellose , hydtoxypropyl
methylcellulose, hydroxy propyl cellulose, pregelatinised starch or macrocrystalline
cellulose. The base material can be used or in mixture with others based on the
conditions during formulation of dosage.
In order to improve /develop the properties of the strip thin film of the dosage form,
well known plasticizers like polyethylene glycol, polypropylene glycol or their mixture is
present in required amount. To achieve capacity in the strip/thin film, commercial grade
inactive titanium dioxide is provided to the dosage form in required amount.
Since the strip/ thin film axe made from the drugs that taste bitter, presence of
sweetness cannot work only. It is very much important to put flavours and approved
colours of desirable amount.
Following are the components in the dosage form in their respective proportions.

Thin film /strip % in the composition
Active ingredients in the strip Pharmaceutically effective amount
Base material 10-75
Sweetness 15-35
Plasticizers 545
Titanium Dioxide 42-60
Flavours & colours Quantity desired for best taste
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The dissolution profile of the invented dosage form with respect to a branded tablet containing same active ingredient (i.e. drug) is studied and the following results are
realised.

Invented product containing olazapene as drug of dosage 250 mg Tablet containing olanzapene as a drug of dosage 250 mg available in brand names
Time in min Release profile (%) Time in min. Release profile (%)
1 75 1 NIL
2 100 2 2
5 — 5 15
10 .. 10 25
20 — 20 50
45 ~ 45 70
1 hr — 1 hr 90
The above study shows that the dosage form available in form of strip /thin film process high degree of dissolution than the branded products. It is also demonstrated that the bitter taste of the dosage form is negligible and even children take it easily. Following is the process adopted for the manufacture of the oral strip/thin film dosage form.
Cellulose paste including ingredients like hypromellose , hydroxypropyl methyl cellulose, hydroxyl propyl cellulose, pregelatinised starch or microcrysttaline cellulose or mixture thereof is prepared in a jacketed mixture and stored for the preparation. A solution of required strength of active ingredient is made either in water, acetone or alcohol or in a mixture of these solvents. The drug solution thus prepared is added to the cellulose paste prepared above with constant stirring for uniform distribution in the cellulose paste.
To the cellulose paste sweetness of required amount are added followed by plasticizer and titanium dioxide. Lasdy flavours and approved colours are further added to impact flavour and colour to the strip / film.
The above — prepared slurry containing different components with their required quantity is carried out to the feed tank on the processing machine. Then the processing machine dispenses the slurry with extra and measured precision form formation of oral strip sheet. The formed strip is then passed to the drier for drying strip so formed. As drying is over these oral strip are then wound on the master reel. In the
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I stage of dispensing of the slurry care is taken maintaining extra precision so that the strip/thin firm so formed should be reality dissolvable dosage in the mouth. The master reels are then loaded on the packaging machine and cut into individual sealed in aluminium pouches and heat sealed. The packaging unit is perfectly synchronized with the dispenser where the strips ate formed for better packing of the end product.
Advantage of the invention
1. This novel dosage form is termed as mouth dissolving strip/
film of a drug. These strip when placed on tongue dissolves in fast 10 seconds and gives effect within two minutes.
2. The fear of bitterness of drugs is avoided due to higher concentration of sweetness in the strip
3. Very easy to administer.
4. Easy acceptability in children as before realization the medicines is administered
5. Gives a fast relief with accuracy of dosing.
While the present invention is described above in connection with preferred or illustrative embodiments, these embodiments ate not intended to be exhaustive or limiting of the invention. Rather, the invention is intended to cover all alternatives, modifications and equivalents included within its scope.
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WE CLAIM
1. A pharmaceutical oral dosage form of easy and rapid dissolution in the mouth comprising of pharmaceutical active ingredient in an effective amount, cellulose as the base, sweeteners, plasticizers, flavours and colours and titanium dioxide characterised in that the flavoured sachet dosage form is a thin film or strip.
2. A pharmaceutical oral dosage form as claimed in claim 1, characterised in that the pharmaceutically active ingredients are selected from diphenhydramine hydrochloride, phentanyl, dextromethorphan hydrobromide, amoldipine besylate, domperidone, diclofenac sodium, risperidone, tolterodine tartarate, loperamide hydrochloride, cetrizine dihydrochloride, Zolpidem tartarate, olanzapene, fluoxetine hydrochloride, montelukast sodium, atorvastatin calcium, isosorbide mononitrate, enalapril maleate, piroxicam or alprazolam.
3. A pharmaceutical oral dosage form as claimed in claim 1, characterised in that the cellulose base are selected from hypromellose, hydroxypropyl methyl cellulose, hydroxyl propyl cellulose, pregeiatinised starch or microcrystalline cellulose or a mixture thereof.
4. A pharmaceutical oral dosage form as claimed in claim 1, characterised in that the sweeteners are selected from maltodextrin, sucralose, sorbitol or mixture thereof
5. A pharmaceutical oral dosage form as claimed in claim 1, characterised in that the plasticizers are selected from polyethylene glycol, propylene glycol, or mixture thereof.
6. A pharmaceutical oral dosage form as claimed in claim 1, characterised in that the titanium dioxide is added to dosage form to impart opacity to the thin film/strip.
7. A process for manufacturing a pharmaceutical dosage form as claimed in claim 1, comprising the steps of :
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(i). preparing a solution of the active ingredient in a suitable solvent.
(ii) adding sweeteners, plastcizers, titanium dioxide, cellulose base and
flavours and colours of desired amount to the content of step (i);
(iii) Carrying out the contents of step (ii) to the feed tank of the processing machine;
(iv) - dispensing the contents of the step (iii) with extra precision for formation of oral strip/film by the dispensing apparatus;
(v) drying the completed oral strip through a dryer;
(vi) making wound of the dried oral strip : / film on the master reel;
(vii) Cutting the master reel into individual strips in the packing machine and sealing in pouch.
A process for manufacturing a pharmaceutical oral dosage form as claimed in
claim; 7 characterise been that the solvents for dissolution of the active
ingredients are selected from water, acetone, alcohol or a mixture thereof.
A pharmaceutical oral dosage form of thin film/strip as herein described with
reference to the description .
A process for manufacturing the pharmaceutical dosage of as herein described
with reference to the description.

ABSTRACT OF THE INVENTION
The present invention discloses a novel pharmaceutical oral dosage form in form of thin strip/ film employing various drugs tasting bitter. Other pharmaceutical adjuvants to improve the properties of the film /strip is disclosed including adding sweeteners and flavours to suppress the bitterness of the drugs carrying bitter taste. The very delicate dosage form requires special provision for manufacturing via specially designed apparatus and that is adopted in order to carry out the invention.
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