Extended release, abuse deterrent pharmaceutical compositions
View Patent ↗Pharmaceutical compositions comprising at least one active pharmaceutical ingredient or a pharmaceutically acceptable salt thereof, at least one hydrophilic plastomer, at least one hydrophilic elastomer, and at least one deliquescent plasticizer, wherein the pharmaceutical compositions provide extended release of the API and have abuse deterrent properties. Methods for preparing the pharmaceutical compositions in which the components of the composition are humidified such that the deliquescent plasticizer deliquesces, thereby plasticizing the hydrophilic polymers.
1. A pharmaceutical composition comprising at least one active pharmaceutical ingredient (API) or a pharmaceutically acceptable salt thereof, at least one hydrophilic plastomer, at least one hydrophilic elastomer chosen from a carbomer, a polycarbophil, or a combination thereof, and at least one deliquescent plasticizer chosen from an organic acid, a sugar alcohol, a co-processed mixture of (i) an organic acid and/or a sugar alcohol and (ii) a liquid plasticizer, or a combination thereof, wherein the pharmaceutical composition is a solid dosage form prepared by a process comprising:
(a) forming a mixture comprising the at least one API or pharmaceutically acceptable salt thereof, the at least one hydrophilic plastomer, the at least one hydrophilic elastomer, and the at least one deliquescent plasticizer, wherein the mixture is a powder, a granulate, or a solid dosage unit;
(b) humidifying the mixture of (a) to form a humidified powder, a humidified granulate, or a humidified solid dosage unit, wherein the humidifying occurs at a temperature and at a relative humidity such that the deliquescent plasticizer undergoes deliquescence;
(c) optionally forming the humidified powder or the humidified granulate of (b) into a treated solid dosage unit;
(d) optionally coating the humidified solid dosage unit of (b) or the treated solid dosage unit of (c) to form a coated solid dosage unit; and
(e) heating the humidified solid dosage unit of (b), the treated solid dosage unit of (c), or the coated solid dosage unit of (d) to form the solid dosage form of the pharmaceutical composition.
2. The pharmaceutical composition of claim 1 , wherein the composition provides extended release of the API and has abuse deterrent properties.
3. The pharmaceutical composition of claim 1 , wherein the at least one hydrophilic plastomer is chosen from a cellulose ether, a polyalkylene oxide, a polyalkylene glycol, a polyolefinic alcohol, a polyvinyl lactam, a polycarboxylic acid, a polysaccharide, a polypeptide, or a combination thereof, and is present in an amount from about 10% to about 90% by weight of the pharmaceutical composition.
4. The pharmaceutical composition of claim 3 , wherein the at least one hydrophilic plastomer is chosen from hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyethylene oxide, or a combination thereof.
5. The pharmaceutical composition of claim 1 , wherein the hydrophilic elastomer is present in an amount from about 0.5% to about 40% by weight of the pharmaceutical composition.
6. The pharmaceutical composition of claim 1 , wherein the deliquescent plasticizer is present in an amount from about 2% to about 50% by weight of the pharmaceutical composition.
7. The pharmaceutical composition of claim 1 , wherein the solid dosage form further comprises a film coating.
8. The pharmaceutical composition of claim 1 , wherein the at least one hydrophilic plastomer comprises hydroxypropyl cellulose, hydroxypropylmethyl cellulose, and polyethylene oxide and is present in an amount from about 50% to about 80% by weight of the composition; the hydrophilic elastomer is a carbomer and is present in an amount from 0.5% to about 10% by weight of the composition; and the deliquescent plasticizer comprises citric acid and sorbitol and is present in an amount from about 10% to about 30% by weight of the composition.
9. The pharmaceutical composition of claim 8 , wherein the API is oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, or morphine.
10. The pharmaceutical composition of claim 1 , which deters abuse by forming a viscous mixture or gel when contacted with 10 mL or less of an aqueous solvent.
11. The pharmaceutical composition of claim 1 , wherein the relative humidity at step (b) is from about 40% to about 100% at 25° C.
12. The pharmaceutical composition of claim 1 , wherein the heating step (e) occurs at a temperature from about 50° C. to about 90° C.
13. The pharmaceutical composition of claim 1 , which deters abuse by breaking into a plurality of particles having an average diameter of greater than about 250 microns when crushed, ground, or pulverized.