Stabilization of solid drug formulations
Pharmaceutical formulations and dosage forms are provided having improved stability to moisture-induced degradation when compared with conventional dosage forms, especially tablets. The invention features low compression forms of drugs known to be susceptible to moisture-induced degradation together with excipients, preferably in encapsulated forms. In other embodiments, relatively non-volatile oils can be admixed with the drug and/or the excipients to stabilize the formulation toward moisture-induced degradation. Hydrophobic powders are also optionally added to the formulations.
1 . A drug dosage form comprising a compound susceptible to moisture-induced degradation and at least one pharmaceutically acceptable excipient prepared under conditions of low compression.
2 . The drug dosage form of claim 1 comprising a capsule.
3 . The drug dosage form of claim 1 comprising a capsule formed of hydroxypropyl methylcellulose.
4 . The drug dosage form of claim 1 wherein the compound is contained in solid form within a capsule.
5 . The drug dosage form of claim 1 wherein the form is subjected to no compression in excess of about 10,000 psi/g.
6 . The drug dosage form of claim 1 wherein the form is subjected to no compression in excess of about 5,000 psi/g.
7 . The drug dosage form of claim 1 wherein the form is subjected to no compression in excess of about 2,000 psi/g.
8 . The drug dosage form of claim 1 wherein the excipient is hydroxypropyl methylcellulose, carboxymethyl cellulose, microcrystalline cellulose, amorphous silicon dioxide, magnesium stearate, starch, sodium starch glycolate, or a combination thereof.
9 . The drug dosage form of claim 1 wherein the excipient has a residual moisture content of less than about 10% by weight.
10 . The drug dosage form of claim 1 exhibiting improved stability to moisture-induced degradation of the compound as compared with a tabletted form of the compound.
11 . The drug dosage form of claim 1 comprising a unit dosage form.
12 . A drug dosage form for a compound susceptible to moisture-induced degradation comprising the compound admixed with a substantially non-volatile, pharmaceutically acceptable oil.
13 . The drug dosage form of claim 12 wherein the oil is an animal or vegetable oil.
14 . The drug dosage form of claim 12 wherein said oil is olive, corn, peanut, nut, soy, rapeseed, cottonseed, vitamin E, fish, or tallow-derived oil.
15 . The drug dosage form of claim 12 wherein the oil is a mineral oil or silicone oil.
16 . The drug dosage form of claim 12 wherein the compound—oil admixture is present within a capsule.
17 . The drug dosage form of claim 12 wherein the compound—oil admixture is present within a soft shell capsule.
18 . The drug dosage form of claim 12 wherein the compound—oil admixture is present within a specially sealed hard-shell capsule.
19 . The drug dosage form of claim 12 wherein at least some of the compound—oil admixture is adsorbed on a pharmaceutically acceptable excipient.
20 . The drug dosage form of claim 12 wherein the excipient having the compound—oil admixture adsorbed thereupon is within a capsule.
21 . The drug dosage form of claim 12 wherein the excipient having the compound—oil admixture adsorbed thereupon is within a tablet.
22 . A drug dosage form for a compound susceptible to moisture-induced degradation comprising the drug and a pharmaceutically acceptable excipient admixed with a substantially non-volatile, pharmaceutically acceptable oil.
23 . The drug dosage form of claim 22 wherein the oil is an animal or vegetable oil.
24 . The drug dosage form of claim 22 wherein said oil is olive, corn, peanut, nut, soy, rapeseed, cottonseed, vitamin E, fish, or tallow-derived oil.
25 . The drug dosage form of claim 22 wherein the oil is a mineral oil or silicone oil.
26 . The drug dosage form of claim 22 wherein the drug and the excipient—oil admixture are present within a capsule.
27 . The drug dosage form of claim 22 wherein the drug and the excipient—oil admixture are present within a tablet.
28 . A drug dosage form comprising a compound susceptible to moisture-induced degradation admixed with a first pharmaceutically acceptable oil together with a pharmaceutically acceptable excipient admixed with a second pharmaceutically acceptable oil.
29 . The drug dosage form of claim 28 wherein the first and the second pharmaceutically acceptable oils are, independently, an animal or vegetable oil.
30 . The drug dosage form of claim 28 wherein the first and the second pharmaceutically acceptable oils are, independently, olive, corn, peanut, nut, soy, rapeseed, cottonseed, vitamin E, fish, or tallow-derived oil.
31 . The drug dosage form of claim 28 wherein the first and the second pharmaceutically acceptable oils are independently, a mineral oil or silicone oil.
32 . The drug dosage form of claim 28 wherein the compound—oil admixture and the excipient—oil admixture are present within a capsule.
33 . The drug dosage form of claim 28 wherein the compound—oil admixture and the excipient—oil admixture are present within a tablet.
34 . A drug dosage form comprising a compound susceptible to moisture-induced degradation and at least one pharmaceutically acceptable hydrophobic powder.
35 . The drug dosage form of claim 34 wherein the hydrophobic powder is triturated directly with the compound.
36 . The drug dosage form of claim 34 wherein the hydrophobic powder is magnesium stearate.
37 . A method for administering a compound susceptible to moisture-induced degradation to a patient comprising providing a unit dose of the compound which has not been processed employing high compression.
38 . A method for administering a compound susceptible to moisture-induced degradation to a patient comprising providing a unit dose of the compound admixed with a substantially non-volatile, pharmaceutically acceptable oil.
39 . The method of claim 38 wherein the compound—oil admixture is present within a capsule.
40 . The method of claim 38 wherein the compound—oil admixture is adsorbed on a pharmaceutically acceptable excipient.
41 . A method for administering a compound susceptible to moisture-induced degradation to a patient comprising providing a unit dose of the compound and a pharmaceutically acceptable excipient admixed with a substantially non-volatile, pharmaceutically acceptable oil.
42 . A method for administering a compound susceptible to moisture-induced degradation to a patient comprising providing a unit dose of the compound and at least one pharmaceutically acceptable hydrophobic powder.