Pharmaceutical composition for rapid suspension in water

• US 5,306,506 A
• Filed: 03/03/1992
• Issued: 04/26/1994
• Est. Priority Date: 07/11/1990
• Status: Expired due to Fees

• Current Assignee: Eurand International S.p.A. (Abbvie Incorporated)
• Original Assignee: Eurand International S.p.A. (Abbvie Incorporated)
• Inventors: Mapelli, Luigi G., Marconi, Marco G., Zema, Marco
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Spear, James M.
• Application Number:
  US07/838,818
• Time in Patent Office: 784 Days
• Field of Search: 424/466, 424/489, 424/490, 424/493, 424/494
• US Class Current: 424/466
• CPC Class Codes: A61K 9/0007 Effervescent A61K9/0065 takes precedence
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: F02B 2275/14 Direct injection into combustion chamber

Abstract

The invention provides a solid pharmaceutical composition for addition to water to produce a suspension of a drug comprising (a) a drug which is substantially water-insoluble or microencapsulated; (b) a thickening or suspending agent; (c) a pharmaceutically acceptable acid; (d) a pharmaceutically acceptable carbonate or bicarbonate; characterised in that the weight ratio of c+d:b is from 1:1.5 to 1:15 and the amount of c+d is sufficient to obtain rapid hydration of the thickening or suspending agent (b) when the composition is mixed with water such that a homogeneous suspension of the drug is obtained within 30 seconds. A method for preparing the composition is also described.

Claims

1. A solid pharmaceutical composition for addition to water to produce a suspension of a drug comprising a mixture of

a) a drug which is substantially water-insoluble or microencapsulated;

with granules comprising an inert carrier coated with an intimate mixture consisting essentially of

b) a thickening or suspending agent;

c) a pharmaceutically accepted acid;

d) a pharmaceutically acceptable carbonate or bicarbonate;

characterized in that the weight ratio of c+d;

b is from 1;

1.5 to 1;

15 and the amount of c+d is sufficient to obtain rapid hydration of the thickening or suspending agent b) when the composition is mixed with water such that a homogeneous suspension of the drug is obtained within 30 seconds.

2. A composition as claimed in claim 1, wherein the weight ratio of c+d:

b is from 1;

1.5 to 1;

5.

3. A composition as claimed in claim 1, wherein the weight ratio of c:

d is from 1;

0.5 to 1;

1.5.

4. A composition as claimed in claim 1 wherein the acid is selected from the group consisting of tartaric, citric, pyruvic, maleic, ascorbic and fumaric acids.

5. As composition as claimed in claim 1, wherein the carbonate or bicarbonate d) is selected from the group consisting of sodium bicarbonate, potassium bicarbonate, sodium carbonate and other water soluble carbonic acid salts.

6. A composition as claimed in claim 1, wherein the thickening or suspending agent is selected from the group consisting of alginates, carrageenin, agar-agar, tragacanth gum, xanthan gum, guar gum, caroba gum, karaya gum, modified corn starch, carboxylmethylcellulose, crystalline cellulose, and mixtures thereof.

7. A composition as claimed in claim 1 wherein the composition contains a binding agent.

8. A composition is claimed in claim 7, wherein the binding agent is selected from the group consisting of methylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxybutylcellulose, polyethyleneglycol, polyvinyl alcohols, polyvinylpyrrolidone, gelatine, amides and modified amides.

9. A composition as claimed in claim 1 further comprising one or more excipients selected from the group consisting of sucrose, lactose, mannitol, anhydrous sorbitol, maltodextrine, glycine, alanine and pentaerythrite.

10. A composition as claimed in claim 1 comprising a surfactant.

11. A composition as claimed in claim 1 wherein a microencapsulated drug is used.

12. Sachets containing unit doses comprising a composition as claimed in claim 1.

13. A method for preparing a pharmaceutical composition which method comprises mixing granules comprising an inert carrier coated with an intimate mixture of b) a thickening or suspending agent, c) a pharmaceutically acceptable acid, d) a pharmaceutically acceptable base selected from the group consisting of carbonates and bicarbonates with a) a water insoluble or microencapsulated drug;

wherein the ratio of c+d;

b is from 1;

1.5 to 1;

15 and the amount of c+d is sufficient to obtain rapid hydration of the thickening or suspending agent b) when the composition is mixed with water such that a homogeneous suspension of the drug is obtained within 30 seconds.

14. A method as claimed in claim 13, wherein the thickening or suspending agent b) has the same granulometry as the acid c) and base d).

15. A method as claimed in claim 13, wherein the ingredients b, c and d are mixed in a non-aqueous solvent, then applied to a water soluble excipient and the mixture dried and then mixed with the drug.

16. A method as claimed in claim 14, wherein the granulometry is less than 150 μ

m.

17. A method as claimed in claim 13, wherein the ingredients b, c and d are mixed to form a homogeneous suspension in a non-aqueous solvent in which a binder is dissolved and in which the ingredient b) is substantially insoluble, the suspension is applied to a water soluble excipient and dried, then mixed with the drug.

18. A method as claimed in claim 17, wherein the excipient is selected from the group consisting of sucrose, lactose, fructose, mannitol, anhydrous sorbitol, maltodextrin, glycine, alanine and pentaerythrite.

19. A pharmaceutical composition prepared by the method described in claim 13.