WO2010067151A1

WO2010067151A1 - Quick disintegrating taste masked composition

Info

Publication number: WO2010067151A1
Application number: PCT/IB2009/007032
Authority: WO
Inventors: Arvind Kumar Bansal; Vibha Puri; Gunjan Kohli; Rama Rao Poduri
Original assignee: National Institute Of Pharmaceutical Education And Research
Priority date: 2008-12-08
Filing date: 2009-10-05
Publication date: 2010-06-17

Abstract

The present invention provides a quick disintegrating taste masked solid preparation for administering mineral compounds. A quick disintegrating taste masked oral solid preparation comprising of a mineral compound, at least one sweetener in weight ratio of sweetener to active range from 3.5 to 7.3 by weight, at least one disintcgrant, and at least one diluent wherein the diluent is selected from, lactose, starch and dibasic calcium phosphate.

Description

"QUICK DISINTEGRATING TASTE MASKED COMPOSITION"

FIELD OF THE INVENTION

The present invention provides a pharmaceutical composition. Particularly, relates to quick disintegrating and taste masked composition of minerals and their salts. H also relates to a process of preparation of the composition.

BACKGROUND AND PRIOR ART

Oral solid dosage forms are the most widely accepted means of administering medications. However, patients at the extremes of age such as children and elderly often experience difficulty in swallowing intact tablets, capsules etc., The solid oral products when ingested produce nauseating effect and are also limited by the maximal size which can be taken by the patient conveniently. Due to such practical problems these dosage forms are not preferred and many a times lead to rejection of therapy by the patient.

Rapidly dispersible and orally disintegrating tablets provide an advantage in such situations. They combine the convenience of solid dosage forms and also provide comfortable dosing to the patients. These dosage forms disintegrate in the oral cavity with or without the aid of liquid. Thus such dosage forms are preferred for pediatric and geriatric patients.

The nutritional supplements such as minerals and vitamins are prescribed to children in treatment of diarrhea and other illness needing mineral salts supplementation. Zinc containing compositions are prescribed to significantly reduce the severity of diarrhea. However, "in-mouth" disintegrating dosage forms release the bitter active principle in the mouth cavity and present another challenge of effectively taste masking the urpleasant bitter active principle.

One of the most preferred ways of administering minerals to pediatric population would be through a quick disintegrating or a mouth dissolving (orally disintegrating) tablet with effective taste masking of the metallic bitter aftertaste produced by mineral compounds. The US patent no. 5059416 discloses a dual encapsulation system for delivering zinc compounds, wherein the unpleasant taste of such compounds is masked by giving first a hydrophilic coating comprises of a film forming hydrophilic material and a second hydrophobic coating comprising of fat and a wax component.

The US Patent No. 6156332 discloses method for reducing unpleasant taste or after taste caused by the presence of mineral in an ingestible product by adding to said ingestible product a flavor masking agent selected from the group consisting of tannic acid, glycyrrhizin, acesulfame potassium and two or more thereof sufficient to reduce the unpleasant taste or aftertaste caused by the mineral.

The US Patent No. 6169118 discloses an orally administered formulation comprising about 0.1 to 25 wt. % of an ionizable zinc compound having undesirable taste, and a synergistic flavoring combination of at least two flavoring oils and lauryl alcohol in an amount effective to mask the undesirable taste of said ionizable zinc compound.

US Patent No. 7182959 discloses a solid dosage form which is rapidly dissolving in aqueous medium. The process comprises (a) preparing a powder or granulate consisting of (1) either the active substance or part thereof and all other ingredients of the solid dosage form: or (2) all other ingredients of the solid dosage form except the active substance; (b) dispensing (1) either an auxiliary solvent or (2) a solution or dispersion (preferably a solution) of the active substance in an auxiliary solvent, in moulds or in the cavities of the pre-formed container intended for storage of the solid dosage form; (c) compacting a suitable amount of the powder or granulate prepared according to a (1) or a (2) as above; (d) putting the compacted powder or granulate so obtained on the top of the liquid which according to b (1) or b (2) is in moulds or in the cavities of the preformed container intended for storage of the solid dosage form; (e) removing the auxiliary solvent by applying a drying system to the units in the moulds or in the cavities of the pre-formed container intended for storage of the solid dosage form; and (f) removing the dried units from the moulds into a suitable storage container or scaling the cavities of the pre-formed container intended for storage of the solid dosage form. respectively. US Patent. No. 6704341 discloses taste masking rapid release coating system comprising a core containing a drug encased in a spacing layer and a taste masking layer composed of a material which is insoluble in saliva at a neutral to basic pH and completely soluble in saliva at a pH of less than about 6.5.

The above cited references appear to disclose compositions of methods of taste masking nutritional supplements. However, none of the above cited references appear to disclose a rapidly disintegrating composition with taste masked minerals or their salts.

Further, above cited references of taste masked composition involve multiple sequential steps and require diligent control of process. To remedy the said existing problems in the art, the invention provides quick disintegrating and taste masked solid composition for administration of mineral compounds.

OBJECTS OF THE INVENTION

The main object of the invention is to provide a quick disintegrating and taste masked solid composition of mineral compounds.

Another object of the invention is to provide a suitable method for manufacture of the formulation.

SUMMARY OF INVENTION

Accordingly the present invention provides a quick disintegrating and taste masked composition of active mineral compounds with other pharmaceutically acceptable ingredients.

In particular the composition allows for the easy swallowing of tablet by children's and elderly patients.

DETAILED DESCRIPTION OF THE INVENTION

The term 'quick disintegrating' as used herein is intended to describe tablets which disintegrate when placed in oral cavity or in small amount of water in less than a minute. Also the term 'quick disintegrating' describes tablets which will disperse easily and quickly after a gentle bite when taken orally. The term 'active principle' is intended to mean a mineral compound and its salt thereof to be administered.

Mineral compounds have metallic bitter aftertaste and unpalatable to mouth. This unpleasant taste can be masked by judicious selection of pharmaceutical additives. In a general aspect of the present invention, there is provided a quick disintegrating and taste masked oral solid preparation comprising of a mineral compound as the active, at least one sweetener where in the weight ratio of sweetener to active ranges from 3.5 to

7.3, at least one disintegrant, and at least one diluent and any other pharmaceutically acceptable excipients.

Embodiments of the invention include following features. The active principle is a mineral compound, preferably a metal ion or its salt selected from the group of iron, copper, zinc, magnesium.

The sweetener is selected such that their physico-chemical properties help in achieving the final composition. The sweetener comprises preferably at least one or combination of a strong sweetener and a mild sweetener. The strong sweetener is preferably a natural origin sweetener preferably stevia or is selected from the group ol^" aspartame, sodium saccharin, acesulfame K, glucose, sucralose and sucrose. The mild sweetener is selected from the group of mannitol, xylitol, maltitol, maltitol, sorbitol and mixtures thereof.

In an embodiment of the present invention, the strong sweetener is a naturally occurring sweetener preferably stevia. Processed stevia is derived from the plant stevia, where the whole leaf extract consists of intensely sweet glycosides such as steviosides, rebaudiosides and dulcoside.

Mannitol acts as a mild sweetener and as a diluent in the formulation. Mannitol and is nonhygroscopic and a directly compressible sugar, which improves processibility of the bulk. It has low water content (weight by weight) and shows no tendency to pick up moisture. It can be blended with active principle to improve their compression and flow properties. In another embodiment of the present invention, there is provided a preparation wherein the sweetener to active weight ratio ranges from 3.5 to 7.3, preferably ranges from 3.6 to 5.3.

In an embodiment of the present invention, the quick disintegrating taste masked oral solid preparation comprising of at least one non-cellulosic disintegrant selected from the group of sodium starch glycolate, crospovidone. polacrillin potassium, sodium alginate. The preparation according to the present invention wherein preferably disintegrant is sodium starch glycolate or crosslinked polyvinylpyrrolidone used alone or in combination.

In an embodiment of the present invention, the quick disintegrating taste masked oral solid preparation comprising of at least one non-cellulosic diluent. The quick disintegration of tablet is achieved by incorporating suitable type and optimal amount of diluent. The diluent is selected from, lactose, starch and calcium phosphate used alone or in combination. Dibasic calcium phosphate and lactose arc nonhygroscopic and are unaffected in ambient conditions (i.e. humidity at room temperature).

In another aspect there is provided a preparation comprising of at least one non- cellulosic disintegrant and a non-cellulose diluent.

Lubricants may be selected from the group that includes talc, stearic acid and its salt. sodium stearyl fumarate, hydrogenated vegetable oil, polyethylene glycols and the like. The glidant may be selected from the group that includes talc, colloidal silicon dioxide and the like. Suitable flavoring agents were used selected from orange, pineapple, grapefruit, cherry, rasberry and the like.

In another aspect there is provided process. for preparation of a quick disintegrating and taste masked solid preparation according to the present invention comprising steps of dry blending of formulation components including mineral compound, sweetener, disintegrants, diluent and optionally other pharmaceutically acceptable cxcipients. or dry or wet granulation of the entire or partial amount of diluent and disintegrant either alone or in combination with the active ingredient to form a granular blend; followed by blending of the mass with remaining section of components; and compressing the homogenous blend into tablets. The flavoring agent may be added in the inlragranular mix or optionally in the extragranular mix.

The invention provides a composition that is robust and nonhygroscopic in ambient environmental conditions of temperature and relative humidity. It also provides ability to operate in already existing manufacturing set up reducing the cost of manufacturing and thus the cost of product.

Following examples are provided to further explain the present invention. The examples provided above are not meant to be exclusive and the scope of the present invention should not be limited by these examples.

EXAMPLES:

The compositions 1, 2, 3, 4 and 5 of oral tablets according to the invention are given below:

Example 1

Table 1

Quantity/Tablet (mg/tab)

Components Composition 1 Composition 2 Composition 3

Zinc sulphate 54.5 54.5 54.5

Aspartame 50.0 50.0 -

Stevia - - 30.0'

Mannitol 157.1 157.1 177. 1

Orange flavor 2.75 2.75 2.75

Sodium starch glycolate 38.5 38.5 38.5

Lactose 41.5 - -

Dicalcium phosphate - 41.5 41 .5

Cornstarch 197.4 197.4 197.4

Colloidal silicon dioxide 2.75 2.75 2.75

Magnesium stearate 5.5 5.5 5.5

Total tablet weight 550 550 550

Manufacturing Process: Dry blending process

a) All ingredients were weighted accurately and sifted through BSS#30. b) Ingredients zinc sulphate, aspartame/stevia, mannitol, orange flavor were sifted together form BSS #30 and transferred into blender for mixing for lOmins.

c) Sodium starch glycolate, dicalcium phosphate/lactose and starch were together sifted through BSS#30 and added to step (b) mass. Blending was continued for 15mins.

d) To the mass of step (c), Colloidal silicon dioxide was added and continued blending for lOmins.

e) Sifted magnesium stearate through BSS#44 and added to step (d) mass, and mixed for 5mins.

f) Compressed the blend of step (e) on a multi-station compression machine.

Exampld

Table 2

Components Quantity/Tablet (ing/tab)

Composition 4

Intragranular

Zinc sulphate 54.5

Mannitol 100.0

Sodium starch glycolate 15.0

Starch 100.0

Magnesium stearate 2.5

Extragranular

Aspartame 50.0

Mannitol 57.1

Sodium starch glycolate 23.0

Dicalcium phosphate 41.5

Starch 97.9

Orange flavor 2.75

Colloidal silicon dioxide 2.75

Magnesium stearate 3.0

Total tablet weight 550 . Manufacturing Process: Dry granulation process

a) All ingredients were weighted accurately and sifted through BSS//30.

b) Intragranular portion of active and other ingreidients was sifted through BSS//30 and blending for 15mins and then lubricated for 5mins.

c) The blend of step (b) was compacted on roller compactor to produce compacts.

d) The step (c) compacts were milled to achieve granular blend

e) The extragranular ingredients were sifted together form BSS#30 and blended with step (d) mass for 15mins.

f) Sifted extragranular magnesium stearate through BSS#44 and added to step (c) mass, and mixed for 5mins.

g) Compressed the final blend of step (f) on a multi-station compression machine.

Example 3

Table 3

Components Quantity/Tablet (mg/tab)

Composition S

Intragranular

Sodium starch glycolate 15.0

Starch 100.0

Extragranular

Zinc sulphate 54.5

Aspartame 50.0

Mannitol 157.1

Sodium starch glycolate 23.0

Dicalcium phosphate 41.5

Starch 97.9

Orange flavor 2.75

Colloidal silicon dioxide 2.75

Magnesium stearate 5.5

Total tablet weight 550 Manufacturing Process: Wet granulation process

a) AU ingredients were weighted accurately and sifted through I3SS#30.

b) lntragranular portion of sodium starch glycolate and starch was sifted through BSS#30 and blended for 15mins and granulated with purified water.

c) The step (b) mass was granulated with purified water in a rapid mixer granulator. The wet mass was dried to achieve dry granular mass.

d) The extragranular ingredients were sifted together from BSS#30 and blended with step (c) mass for 15mins.

e) Sifted extragranular magnesium stearate through BSS#44 and added to step (d) mass, and mixed for 5mins.

f) Compressed the final blend of step (e) on a multi-station compression machine. The properties of the tablets according to the invention are given in 'Table 4 and have been measured as per USP29.

Table 4

Example No. 4

Table 5

Manufacturing steps

♦ Sieve all the contents through BSS #40.

♦ Add accurately weighed Mannitol, Dibasic calcium phosphate and corn starch in a blender and mix the content for 15 minutes. ♦ Make starch paste (10%) using corn starch for paste and water, add to the above- mixture and granulate the mass.

♦ Dry the wet mass at 4O⁰C for 30 min in an FBD. Pass the dried granules through BSS #20. LOD should be in range of 1-2%

♦ Add Zinc sulphate, aspartame and dry flavor pineapple to the above granules and blend for 15 min.

♦ Add Aerosil 200 and sodium starch glycolate and blend for 10 min. ♦ Lubricate the above blend with weighed amount of magnesium stcarate for 5 min.

♦ Compress the tablet using a tablet press.

Although the invention has been described with reference to specific embodiments, this description is not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternate embodiments of the invention, will become apparent to persons skilled in the art upon reference to the description of the invention. It is therefore contemplated that such modifications can be made without departing from the spirit or scope of the present invention as defined.

Claims

WE CLAIM:

1. A quick disintegrating taste masked composition comprising of

(a) an active mineral compound;

(b) a sweetening agent; (c) a disintegrant;

(d) a diluent; and optionally other pharmaceutically acceptable excipient.

2. The composition as claimed in claim 1, wherein the active mineral compound comprises one or more of salts of iron, copper, zinc, magnesium.

3. The composition as claimed in claim 2, wherein the active mineral compound is a salt of zinc metal.

4. The composition as claimed in claim 1, wherein the sweetening agent comprises of one or combination of a strong sweetening agent and a mild sweetening agent.

5. The composition as claimed in claim 4, wherein the strong sweetening agent is a natural origin sweetener or selected from a group comprises of aspartame. sodium saccharin, acesulfame k, glucose, sucralose and sucrose.

6. The composition as claimed in claim 5, wherein a natural origin swcelcner is stevia.

7. The composition as claimed in claim 4, wherein the mild sweetening agent is selected from a group comprising of mannitol, xylitol, maltilol, sorbitol and mixtures thereof.

8. The composition as claimed in claim 1 , wherein a ratio of sweetening agent to active mineral compound ranges is in the range of 3.5: 1 to 7.3: 1 , preferably in the ranges of 3.6: 1 to 5.3: 1.

9. The composition as claimed in claim 1, wherein the disintegrant is a non- cellulosic disintegrant.

10. The composition as claimed in claim 9, wherein the non-cellulosic disintegrant comprises one or combination of sodium starch glycolate, starch and crosslinked polyvinylpyrrolidone.

11. The composition as claimed in claim 1, wherein the diluent is a non-cellulosic diluent.

12. 1 he composition as claimed in claim 11, wherein the non-cellulosϊc diluent comprises one or combination of starch, lactose and dibasic calcium phosphate.

13. The composition as claimed in claim 1, wherein the composition is essentially . free of cellulose and its derivatives.

14. The composition as claimed in claim 1, wherein the pharmaceutically acceptable excipient comprises glidant, and lubricant.

15. The composition as claimed in claim 14, wherein the glidant comprises alone or combination of talc and colloidal silicon dioxide.

16. The composition as claimed n claim 14, wherein the lubricant comprises alone or combination of talc, stearic acid and its salts, sodium stearyl fumaratc, hydrogenated -vegetable oil and polyethylene glycols.

17. The process for preparing the quick disintegrating taste masked composition as claimed in claim 1, said process comprising the steps of (a) mixing the active mineral compound, the sweetener, the disintegrants, the diluent and optionally other pharmaceutically acceptable excipient(s) to obtain a solid mixture; and (b) compressing the solid mixture thus obtained in the form of a tablet.

18. The process as claimed in claim 17, wherein the step (a) the mixing is performed by a dry blending method or a granulation method.

19. The process as claimed in claim 18, wherein the granulation method comprises (a) granulating an entire or partial amount of diluent and disintergrant either alone or in combination with the active mineral compound to form a granular blend; and (b) blending the granulating blend with the sweetener and a remaining amount of the diluent and disintegrant, if any.