Pharmaceutical formulations

• US 4,938,967 A
• Filed: 09/17/1987
• Issued: 07/03/1990
• Est. Priority Date: 09/18/1986
• Status: Expired due to Fees

• Current Assignee: London School of Economics
• Original Assignee: London School of Pharmacy Innovations Limited
• Inventors: Devereux, Jane E., Newton, John M.
• Primary Examiner(s): Robinson, Ellis P.
• Assistant Examiner(s): Horne, Leon R.
• Application Number:
  US07/097,943
• Time in Patent Office: 1,020 Days
• Field of Search: 424/458, 424/459, 424/464, 424/468, 424/470, 424/469, 424/489
• US Class Current: 424/458
• CPC Class Codes: A61K 9/1611 Inorganic compounds

Abstract

The residence time in the human stomach of pharmaceutical, gastric controlled release, solid units can be increased significantly if the units have a density that is much higher than normal. A preferred oral dosage form according to the invention comprises a capsule or other dosage form having a dimension above 2 mm and that contains one or more of the said units. The density of each unit is preferably at least 2.5 and usually at least 2.7 g/ml and can conveniently be achieved by including at least 50% by weight of a weighting agent such as barium sulphate.

Claims

1. An oral, solid, pharmaceutical dosage form that is a capsule or disintegratable tablet and that has a minimum dimension of at least 2 mm and that is suitable for oral administration to humans and that comprises a plurality of controlled release units each comprising a pharmaceutically active ingredient and a pharmaceutically acceptable carrier that includes gastric controlled release binder that will permit controlled release of the active ingredient from the controlled release unit while in the stomach, and in which each said controlled release unit has a density of at least 2.5 g/ml.

2. A dosage form according to claim 1 in which the said density is at least 2.7 g/ml.

3. A dosage form according to claim 1 in which the said density is below 6 g/ml.

4. A dosage form according to claim 1 in which the or each said controlled release unit has a mean dimension of at least about 1 mm.

5. A dosage form according to claim 1 in which each said unit has a mean dimension of about 1 to about 2 mm.

6. A dosage form according to claim 1 in which each said unit is spheronized pellets having a mean diameter of about 1 to about 2 mm.

7. A dosage form according to claim 1 having a maximum dimension of about 5 to about 25 mm and a minimum dimension of below about 10 mm.

8. A dosage form according to claim 1 in which the said carrier of each said controlled release unit includes also about 50% to about 95% by weight of the said unit of a pharmaceutically acceptable weighting agent having a density of at least about 3.0 g/ml.

9. A dosage form according to claim 1 in which the said carrier of each said controlled release unit includes also about 50% to about 95% by weight of the said unit of a pharmaceutically acceptable weighting agent which comprises barium sulphate or ferrous oxide.

10. A dosage form according to claim 1 in which the controlled release binder comprises a controlled release coating around each said controlled release unit.

11. A dosage form according to claim 1 in which the active ingredient is selected from alimentary tract and metabolic products, cardiovascular products, blood and clotting products, neurological products, H₁ antagonists, and products having antiviral activity.

12. A dosage form according to claim 1 in which the active ingredient is a prostaglandin.

17. The oral dosage form of claim 1 in which each controlled release unit has and a mean diameter of not more than about 2 mm.

19. A dosage form according to claim 1 in which the density of each controlled release unit is the same.

13. A method of prolonging the release of an active ingredient within the human stomach when administering orally a solid pharmaceutical dosage form that is a capsule or disintegratable tablet and that has a minimum dimension of at least 2 mm and that comprises a plurality of controlled release units each comprising the said ingredient and a pharmaceutically acceptable carrier that includes a gastric controlled release binder that will permit controlled release of the active ingredient from the unit while in the stomach, the method comprising incorporating into each said controlled release unit at least 50% by weight of a weighting aid having a density of at least about 3 g/ml and thereby increasing the density of each said unit to above 2.5 g/ml.

20. A method according to claim 13 in which the density of each resulting controlled release unit is the same.

14. In a method of releasing an active ingredient within the human stomach by administering orally a solid pharmaceutical dosage form that is a capsule or distingratable tablet and that has a minimum dimension of at least 2 mm and that comprises a plurality of controlled release units each comprising a pharmaceutically active ingredient and a pharmaceutically acceptable carrier that includes gastric controlled release binder that will control release of the active ingredient from the controlled release unit while in the stomach, the improvement which comprises prolonging the release of the active ingredient within the stomach by using, as each controlled release unit, a unit have a density greater than 2.5 g/ml.

15. The method according to claim 14, in which each controlled release unit has and a mean dimension of not more than about 2 mm.

21. A method according to claim 14 in which the density of each controlled release unit is the same.

16. In an oral solid pharmaceutical dosage form that is a capsule or disintegratable tablet and that has a minimum dimension of at least 2 mm and that is suitable for oral administration of humans and that comprises a pharmaceutically active ingredient and a pharmaceutically acceptable carrier that includes gastric controlled release binder that will permit controlled release of the active ingredient from the controlled release unit while in the stomach, the improvement which comprises each said controlled release unit having a density of at least 2.5 g/ml, whereby retention in the stomach of all the units is prolonged.

18. The oral dosage form of claim 16 in which the density of each controlled release unit is the same.