Patent EA-000804-B1 (EA)
Title: Solid dosage form comprising cisapride derivatiive, method preparation thereof, compound comprising solid dosage form, pharmaceutical package
Inventor: GILIS PAUL MARIE VICTOR
IPC: A61K9/20
Filed: 1997-03-20
Abstract: 1. A solid dosage form comprising a pharmaceutically acceptable carrier and as an active ingredient a salt form of cisapride selected from cisapride-(L)-tartrate, cisapride-(D)-tartrate, cisapride-sulfate, cisapride citrate characterized in that the active ingredient dissolves for more than 60% within 1 hour in a pH range from 1 to 7.5 when tested as set forth in USP test <711> in a USP-2 dissolution apparatus, as described in US Pharmacopea XXII, pp 1578-1579. 2. A solid dosage form according to claim 1, characterized in that the active ingredient dissolves for more that 70% after 60 minutes in a pH of 6.5 (USP-buffer) when tested according to claim 1. 3. A solid dosage form according to claims 1 or 2 wherein the salt form is cisapride-(L)-tartrate. 4. A solid dosage form according to claim 3, wherein the diameter of powdered active ingredient ranges from about 10 μm to about 150 μm as measured via laser diffraction. 5. A solid dosage form according to claim 4, wherein the powdered active ingredient used has a specific surface area of more than 14 x 103 cm<2>/g (1.4 x 10<3> m<2>/kg). 6. A solid dosage form as claimed in any of the preceding claims, wherein the solid dosage form is an oral  solid dosage form. 7. A solid dosage form according to claim 6 wherein the oral dosage form is a capsule. 8. A solid dosage form according to claim 6 shaped as a tablet. 9. A solid dosage form according to claim 6 further comprising an antacid, H2-antagonist or a proton pump inhibitor. 10. A solid dosage form according to claim 6 exhibiting a value of (AUCfed)/(AUCfasted of less than 1.25. 11. A tablet according to claim 8 comprising lactose monohydrate and microcrystalline cellulose as fillers. 12. A tablet according to claim 11 wherein the amount of filler ranges from about 50% (w/w) to about 95 % (w/w) based on the total weight of the tablet or tablet core. 13. A tablet according to claim 12 wherein the amount of filler ranges from about 66% (w/w) to about 86 % (w/w) based on the total weight of the tablet or tablet core. 14. A tablet as claimed in claim 13 wherein the disintegrant is crosslinked sodium carboxymethylcellulose (Croscarmellose sodium). 15. A tablet according to claims 8 to 14 wherein the tablet is a film coated tablet. 16. A tablet according to claim 15 wherein the tablet has a tablet core with the following composition: Cisapride-(L)-tartrate 13.23 mg 7.35% lactose monohydrate 200 mesh  107.73 mg 59.85% Unmodified maize starch  36.00 mg  20.00%  HPMC 2910 15 mPa.s  3.60 mg  2.00% Microcrystalline cellulose 1 2.60 mg  7.00% Croscarmellose sodium  5.40 mg  3.00% Colloidal anhydrous silica  0.54 mg  0.30% Magnesium stearate  0.90 mg  0.50% and a coating having the following composition   HPMC 2910 5 mPa.s  4.00 mg  55.94% Propylene glycol  1.00 mg  13.99% Titanium dioxide  1.20 mg  16.78% talc  0.80 mg  11.19%  yellow ferric oxide  0.15 mg  2.10%    wherein the percentages of the tablet core ingredients are % (w/w) based upon the total weight of the tablet core and the percentages of the tablet coating are % (w/w) based upon the total weight of the tablet coating. 17. A tablet according to claims 8 to 16 wherein the tablet has a hardness of at least 1.5 daN measured according to test described in the European Pharmacopeia test (1997) on page 135. 18. A process for preparing an oral solid dosage form as claimed in any of the preceding claims wherein the active ingredient is intimately mixed with the carrier and either filled of into capsules or further formulated into tablets. 19. A process according to claim 18 wherein the active ingredient and the excipients are mixed, compressed into tablets and optionally film-coated. 20. A product containing a solid dosage form according to any of claims 1 to 17 and an antacid, an H2-antagonist or a proton pump inhibitor, as a combined preparation for simultaneous, separate or sequential use in treating gastrointestinal disorders, especially gastro-esophagal reflux related conditions. 21. A pharmaceutical package suitable for commercial sale, comprising a container, an oral dosage form of cisapride which does not exhibit an adverse food effect, and, associated with said package, written matter non-limited as to whether the dosage form can be taken with or without food. 22. Use of cisapride-(L)-tartrate, cisapride-(D)-tartrate, cisapride-sulfate, cisapride citrate for the manufacture of an oral dosage form without drugfood interaction for the treatment of gastrointestinal disorders. 23. Use according to claim 22 wherein oral dosage form can be administered independently from the meal. 24. Use according to claim 22 wherein oral dosage form can be administered during the meal. 25. Use according to claim 22 wherein oral dosage form can be administered together with a proton pump inhibitor, a H2 antagonist or an antacid. 26. Use according to claim 22 wherein oral dosage form can be administered pro re nata. 27. Use of cisapride-(L)-lartrate, cisapride-(D)-tartrate, cisapride sulfate, cisapride citrate for the manufacture of an oral dosage form for the treatment of gastrointestinal disorders in patients taking medication which increases the pH of the stomach. 28. Use according to claim 27 wherein the medication which increases the pH of the stomach is a proton pump inhibitor, H2-inhibitor and an antacid.