Dry mix formulation for bisphosphonic acids
AssigneeMerck & Co., Inc.
InventorsSimon R. Bechard, Kenneth A. Kramer, Ashok V. Katdare
Life of this patent
Estimating the term…
Abstract
Pharmaceutical compositions of bisphosphonic acids, and salts thereof, are prepared by direct compression/dry mix tablet formulation. These pharmaceutical compositions are useful in the treatment of disturbances involving calcium or phosphate metabolism, in particular, the treatment and prevention of diseases involving bone resorption, especially osteoporosis, Paget's disease, malignant hypercalcemia, and metastatic bone disease.
Claims20
A process for the preparation of a tablet containing an active ingredient selected from the group consisting of:
- 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid;
- N-methyl-4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid;
- 4-(N,N-dimethylamino)-1-hydroxybutylidene-1,1-bisphosphonic acid;
- 3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid;
- 3-(N,N-dimethylamino)-1-hydroxypropylidene-1,1-bisphosphonic acid;
- 1-hydroxy-3-(N-methyl-N-pentylamino)propyl-idene-1,1-bisphosphonic acid;
- 1-hydroxy-2-[3-pyridyl]ethylidene-1,1-bisphosphonic acid;
- and
- 4-(hydroxymethylene-1,1-bisphosphonic acid)-piperidine;
- or a pharmaceutically acceptable salt thereof;
- which process comprises:
- forming a mixture by mixing the active ingredient with:
- a diluent, selected from:
- anhydrous lactose and hydrous fast flow lactose,
- a dry binder,
- a disintegrant,
- and optionally one or more additional ingredients selected from the group consiting of:
- compression aids, flavors, flavor enhancers, sweeteners and preservatives;
- lubricating the mixture with a lubricant;
- and
- compressing the resultant lubricated mixture into a desired tablet form.
A pharmaceutical composition comprising by weight, about 0.5 to 40% by weight of an active ingredient selected from the group consisting of:
- 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid;
- N-methyl-4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid;
- 4-(N,N-dimethylamino)-1-hydroxybutylidene-1,1-bisphosphonic acid;
- 3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid;
- 3-(N,N-dimethylamino)-1-hydroxypropylidene-1,1-bisphosphonic acid;
- 1-hydroxy-3-(N-methyl-N-pentylamino)propyl-idene-1,1-bisphosphonic acid;
- 1-hydroxy-2-[3-pyridyl]ethylidene-1,1bisphosphonic acid;
- and
- 4-(hydroxymethylene-1,1-bisphosphonic acid)-piperidine;
- or a pharmaceutically acceptable salt thereof;
- and from about 60 to 99.5% by weight of excipients consisting essentially of:
- anhydrous lactose or hydrous fast flow lactose;
- microcrystalline cellulose;
- croscarmallose sodium;
- and magnesium stearate.
A pharmaceutical composition comprising by weight, about 0.5 to 40% by weight of an active ingredient selected from the group consisting of:
- 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid;
- N-methyl-4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid;
- 4-(N,N-dimethylamino)-1-hydroxybutylidene-1,1-bisphosphonic acid;
- 3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid;
- 3-(N,N-dimethylamino)-1-hydroxypropylidene-1,1-bisphosphonic acid;
- 1-hydroxy-3-(N-methyl-N-pentylamino)propyl-idene-1,1-bisphosphonic acid;
- 1-hydroxy-2-[3-pyridyl]ethylidene-1,1-bisphosphonic acid;
- and
- 4-(hydroxymethylene-1,1-bisphosphonic acid)-piperidine;
- or a pharmaceutically acceptable salt thereof;
- about 10 to 80% by weight of anhydrous lactose or hydrous fast flow lactose;
- about 5 to 50% by weight of microcrystalline cellulose;
- about 0.5 to 10% by weight of croscarmallose sodium;
- and
- about 0.1 to 5% by weight of magnesium stearate.
A process for the preparation of a table containing as active ingredient a basic nitrogen containing bisphosphonate:
- which process comprises:
- forming a mixture by mixing the active ingredient with:
- a diluent, selected from:
- anhydrous lactose and hydrous fast flow lactose,
- a dry binder,
- a disintegrant,
- and optionally one or more additional ingredients selected from the group consiting of:
- compression aids, flavors, flavor enhancers, sweeteners and preservatives;
- lubricating the mixture with a lubricant;
- and
- compressing the resultant lubricated mixture into a desired tablet form.
Dependencies are inferred from the claim text.