Pharmaceutical compositions for minocycline
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.
1. A once daily oral compressed tablet comprising minocycline hydrochloride equivalent to 105 mg of minocycline consisting essentially of
(i) immediate release pellets comprising (a) an inert core having a diameter of 125 to 600 microns, (b) a drug layer on the inert core, the drug layer comprising minocycline hydrochloride and (c) a barrier coating layer, the barrier coating comprising 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, wherein the only minocycline hydrochloride in the immediate release pellets is in the drug layer;
(ii) extended release pellets comprising (a) an inert core having a diameter of 125 to 600 microns, (b) a drug layer on the inert core, the drug layer comprising minocycline hydrochloride 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, wherein the one or more release modifying polymers consist essentially of ethyl cellulose and hydroxy propyl methyl cellulose at a weight ratio of from 65:35 to 85:15 and in an amount of 5% to 10% by weight of the tablet, and the only minocycline hydrochloride in the extended release pellets is in the drug layer; and
(iii) one or more cushioning agents to prevent adhesion of the pellets during compression, the one or more cushioning agents being 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;
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;
minocycline hydrochloride is the sole active ingredient in the tablet;
the immediate release pellets in total include minocycline hydrochloride equivalent to 21 to 42 mg of minocycline, and the extended release pellets in total include minocycline hydrochloride equivalent to 84 to 63 mg of minocycline; and
the tablet having one score line for dividing the tablet into equal subunits to provide a predictable and accurate dose of minocycline and the divided subunits have (i) uniformity of drug content and (ii) 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 tablet of claim 1 , wherein in the immediate release pellets and the extended release pellets are present in a ratio of 20:80 to 40:60.
3. The tablet of claim 1 , wherein the tablet is substantially free of (less than 5% w/w) lactose.
4. The tablet of claim 1 , wherein the immediate release pellets are not coated with one or more release modifying polymers.
5. A once daily oral compressed tablet comprising minocycline hydrochloride equivalent to 135 mg of minocycline consisting essentially of
(i) immediate release pellets comprising (a) an inert core having a diameter of 125 to 600 microns, (b) a drug layer on the inert core, the drug layer comprising minocycline hydrochloride and (c) a barrier coating layer, the barrier coating comprising 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, wherein the only minocycline hydrochloride in the immediate release pellets is in the drug layer;
(ii) extended release pellets comprising (a) an inert core having a diameter of 125 to 600 microns, (b) a drug layer on the inert core, the drug layer comprising minocycline hydrochloride 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, wherein the one or more release modifying polymers consist essentially of ethyl cellulose and hydroxy propyl methyl cellulose at a weight ratio of from 65:35 to 85:15 and in an amount of 5% to 10% by weight of the tablet, and the only minocycline hydrochloride in the extended release pellets is in the drug layer; and
(iii) one or more cushioning agents to prevent adhesion of the pellets during compression, the one or more cushioning agents being 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;
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;
minocycline hydrochloride is the sole active ingredient in the tablet
the immediate release pellets in total include minocycline hydrochloride equivalent to 27 to 54 mg of minocycline, and the extended release pellets in total include minocycline hydrochloride equivalent to 108 to 81 mg of minocycline; and
the tablet having one score line for dividing the tablet into equal subunits to provide a predictable and accurate dose of minocycline and the divided subunits have (i) uniformity of drug content and (ii) 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.
6. The tablet of claim 5 , wherein the immediate release pellets are not coated with one or more release modifying polymers.
7. The tablet of claim 5 , wherein in the immediate release pellets and the extended release pellets are present in a ratio of 20:80 to 40:60.
8. The tablet of claim 5 , wherein the tablet is substantially free of (less than 5% w/w) lactose.
9. The tablet of claim 1 , wherein said tablet is supplied to a pharmacy or stored in a warehouse to provide at least 50% reduced stock keeping units of minocycline tablets.
10. The tablet of claim 5 , wherein said tablet is supplied to a pharmacy or stored in a warehouse to provide at least 50% reduced stock keeping units of minocycline tablets.
11. The tablet of claim 1 , wherein the inert cores of the immediate release pellets and the inert cores of the extended release pellets comprise microcrystalline cellulose.
12. The tablet of claim 5 , wherein the inert cores of the immediate release pellets and the inert cores of the extended release pellets comprise microcrystalline cellulose.
13. The tablet of claim 1 , wherein the coating on the extended release pellets consists essentially of ethyl cellulose, hydroxy propyl methyl cellulose, and a plasticizer.
14. The tablet of claim 13 , wherein the plasticizer is triethyl citrate.
15. The tablet of claim 5 , wherein the coating on the extended release pellets consists essentially of ethyl cellulose, hydroxy propyl methyl cellulose, and a plasticizer.
16. The tablet of claim 15 , wherein the plasticizer is triethyl citrate.
17. The tablet of claim 1 , wherein said tablet exhibits a disintegration time from 5 minutes to 20 minutes in a food dispersion.
18. The tablet of claim 5 , wherein said tablet exhibits a disintegration time from 5 minutes to 20 minutes in a food dispersion.