Pharmaceutical compositions for minocycline

Abstract

The present application relates to a method of orally administering once daily tablet of minocycline to a subject in need thereof, wherein said tablet is substantially free of lactose. The present application also relates to processes for preparing said once daily tablet of minocycline that provides reduced stock keeping units with improved inventory by supplying multiple doses of minocycline in single tablet.

What is claimed is: 
     
         1 . A method of treating acne in a patient in need thereof comprising orally administering once daily to the patient a whole or half a tablet comprising minocycline hydrochloride equivalent to 105 mg or 135 mg of minocycline, where the tablet consists essentially of
 (i) immediate release pellets comprising (a) an inert core, (b) a drug layer comprising minocycline hydrochloride on the inert core, and (c) a barrier coating layer;   (ii) extended release pellets comprising (a) an inert core, (b) a drug layer comprising minocycline hydrochloride on the inert core, and (c) a coating with one or more release modifying polymers to provide extended release of the minocycline hydrochloride in the drug layer of the extended release pellets; and   (iii) one or more cushioning agents to prevent adhesion of the pellets during compression, wherein   the minocycline hydrochloride is the sole active ingredient in the tablet,   about 20 to about 40 percent of the minocycline hydrochloride present in the tablet is present in the immediate release pellets and about 80 to about 60 percent of the minocycline hydrochloride present in the tablet is present in the extended release pellets, and   the tablet has one score line for dividing the tablet into equal subunits to provide a predictable and accurate dose of minocycline, where (i) the divided subunits have uniformity of drug content and (ii) the divided subunits and the intact tablet exhibit similar dissolution profiles when measured in a USP type I apparatus at 100 rpm in 900 ml of simulated gastric fluid with a pH of 2.1 and at 37° C.   
     
     
         2 . The method of  claim 1 , wherein the tablet is substantially free of lactose. 
     
     
         3 . The method of  claim 1 , wherein the inert cores of the immediate release pellets and the inert cores of the extended release pellets comprise microcrystalline cellulose. 
     
     
         4 . The method of  claim 1 , wherein the inert cores of the immediate release pellets and the inert cores of the extended release pellets have a diameter of 125 to 600 microns. 
     
     
         5 . The method of  claim 1 , wherein the barrier coating comprises one or more polymers selected from methyl cellulose, carboxy methyl cellulose, hydroxy propyl cellulose, hydroxy propyl methyl cellulose, polyethylene glycol, starch, and any combination of any of the foregoing. 
     
     
         6 . The method of  claim 1 , wherein the one or more release modifying polymers consist essentially of ethyl cellulose and hydroxy propyl methyl cellulose. 
     
     
         7 . The method of  claim 6 , wherein the weight ratio of ethyl cellulose to hydroxy propyl methyl cellulose is from 65:35 to 85:15. 
     
     
         8 . The method of  claim 7 , wherein the one or more release modifying polymers are present in an amount of 5% to 10% by weight of the tablet. 
     
     
         9 . The method of  claim 1 , wherein the coating on the extended release pellets consists essentially of ethyl cellulose, hydroxy propyl methyl cellulose, and a plasticizer. 
     
     
         10 . The method of  claim 9 , wherein the plasticizer is triethyl citrate. 
     
     
         11 . The method of  claim 1 , wherein the only minocycline hydrochloride in the immediate release pellets is in the drug layer of the immediate release pellets, and the only minocycline hydrochloride in the extended release pellets is in the drug layer of the extended release pellets. 
     
     
         12 . The method of  claim 1 , wherein the one or more cushioning agents are selected from microcrystalline cellulose, silicified microcrystalline cellulose, calcium phosphate, mannitol, sorbitol, polyethylene glycol, sodium stearyl fumarate, magnesium stearate, starch, talc, or any combination of any of the foregoing. 
     
     
         13 . The method of  claim 1 , wherein the amount of cushioning agent(s) in the tablet ranges from 40% to 60% by weight, based upon 100% total weight of the tablet. 
     
     
         14 . The method of  claim 1 , wherein the patient suffers from inflammatory lesions of non-nodular moderate to severe acne vulgaris. 
     
     
         15 . A method of treating acne in a patient having a body weight of 45 to 59 kg comprising:
 (a) dividing a scored tablet containing minocycline hydrochloride equivalent to 105 mg of minocycline along the score line into two equal subunits, and   (b) orally administering to the patient one subunit of the tablet once daily, wherein the tablet consists essentially of
 (i) immediate release pellets comprising (a) an inert core, (b) a drug layer comprising minocycline hydrochloride on the inert core, and (c) a barrier coating layer; 
 (ii) extended release pellets comprising (a) an inert core, (b) a drug layer comprising minocycline hydrochloride on the inert core, and (c) a coating with one or more release modifying polymers to provide extended release of the minocycline hydrochloride in the drug layer of the extended release pellets; and 
 (iii) one or more cushioning agents to prevent adhesion of the pellets during compression, wherein 
   the minocycline hydrochloride is the sole active ingredient in the tablet,   about 20 to about 40 percent of the minocycline hydrochloride present in the tablet is present in the immediate release pellets and about 80 to about 60 percent of the minocycline hydrochloride present in the tablet is present in the extended release pellets, and   the tablet has one score line for dividing the tablet into equal subunits to provide a predictable and accurate dose of minocycline, where (i) the divided subunits have uniformity of drug content and (ii) the divided subunits and the intact tablet exhibit similar dissolution profiles when measured in a USP type I apparatus at 100 rpm in 900 ml of simulated gastric fluid with a pH of 2.1 and at 37° C.   
     
     
         16 . A method of treating acne in a patient having a body weight of 60 to 84 kg comprising:
 (a) dividing a scored tablet containing minocycline hydrochloride equivalent to 135 mg of minocycline along the score line into two equal subunits, and   (b) orally administering to the patient one subunit of the tablet once daily, wherein the tablet consists essentially of
 (i) immediate release pellets comprising (a) an inert core, (b) a drug layer comprising minocycline hydrochloride on the inert core, and (c) a barrier coating layer; 
 (ii) extended release pellets comprising (a) an inert core, (b) a drug layer comprising minocycline hydrochloride on the inert core, and (c) a coating with one or more release modifying polymers to provide extended release of the minocycline hydrochloride in the drug layer of the extended release pellets; and 
 (iii) one or more cushioning agents to prevent adhesion of the pellets during compression, wherein 
   the minocycline hydrochloride is the sole active ingredient in the tablet,   about 20 to about 40 percent of the minocycline hydrochloride present in the tablet is present in the immediate release pellets and about 80 to about 60 percent of the minocycline hydrochloride present in the tablet is present in the extended release pellets, and   the tablet has one score line for dividing the tablet into equal subunits to provide a predictable and accurate dose of minocycline, where (i) the divided subunits have uniformity of drug content and (ii) the divided subunits and the intact tablet exhibit similar dissolution profiles when measured in a USP type I apparatus at 100 rpm in 900 ml of simulated gastric fluid with a pH of 2.1 and at 37° C.