Stabilization of solid drug formulations

Abstract

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.