Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer

A stabilized solid controlled release dosage form comprising a substrate comprising a therapeutically active agent, said substrate overcoated with an aqueous dispersion of plasticized ethylcellulose and cured at a temperature greater than the glass transition temperature of the aqueous dispersion of the plasticized ethylcellulose and at a relative humidity from about 60% to about 100% until an endpoint is reached at which said cured coated substrate provides a stable dissolution profile, said endpoint being determined by comparing the dissolution profile of the formulation immediately after curing to the dissolution profile of the formulation after exposure to accelerated storage conditions of one month at a temperature of 37.degree. C. and at a relative humidity of 80%.

A stabilized controlled release solid dosage form for oral administration, comprising a plurality of inert pharmaceutically acceptable beads coated with a therapeutically active agent, and overcoated with an aqueous dispersion of plasticized ethylcellulose to a thickness effective to obtain a controlled release of said therapeutically active agent when said solid dosage form is exposed to aqueous solutions, said overcoated beads included in said formulation in an amount sufficient to provide a desired therapeutic effect,

• said overcoated beads cured at a temperature greater than the glass transition temperature of the aqueous dispersion of plasticized ethylcellulose and at a relative humidity from about 60% to about 100%, until an endpoint is reached at which said cured overcoated beads provide a stable dissolution profile, said endpoint being determined by comparing the dissolution profile of the formulation immediately after curing to the dissolution profile of the formulation after exposure to accelerated storage conditions of one month at a temperature of 37.degree. C. and at a relative humidity of 80%.

A solid dosage form comprising a plurality of inert pharmaceutically acceptable beads comprising a therapeutically active agent overcoated with an aqueous dispersion of ethylcellulose to a weight gain sufficient to obtain a controlled release of said therapeutically active agent when said dosage form is exposed to aqueous solutions, said solid dosage form being cured after said overcoating is applied at a temperature greater than the glass transition temperature of said aqueous dispersion of ethylcellulose and at a relative humidity from about 60% to about 100% for a time period from about 48 hours to about 72 hours, until said cured coated dosage form exhibits a stable in-vitro release of said therapeutically active agent when exposed to accelerated storage conditions of one month at about 37.degree. C. and 80% relative humidity.

A method of stabilizing a substrate comprising a therapeutically active agent overcoated with an aqueous dispersion of plasticized ethylcellulose in an amount sufficient to obtain a controlled release of the therapeutically active agent when the coated substrate is exposed to aqueous solutions, comprising subjecting the coated substrate to curing at a temperature greater than the glass transition temperature of said aqueous dispersion of plasticized ethylcellulose and at a relative humidity from about 60% to about 100%, for a period of time necessary to obtain a final product which exhibits a stable in-vitro release of said therapeutically active agent when exposed to accelerated storage conditions of one month at 37.degree. C. and 80% relative humidity.

A stabilized solid controlled release dosage form comprising a substrate comprising a therapeutically active agent, said substrate overcoated with an aqueous dispersion of plasticized ethylcellulose to a sufficient weight gain such that a controlled release of said therapeutically active agent is obtained when said dosage form is exposed to aqueous solutions, said overcoated substrate cured at a temperature greater than the glass transition temperature of said aqueous dispersion of plasticized ethylcellulose and at a relative humidity from about 60 to about 100 percent for a time period necessary to obtain a final product which exhibits a stable in-vitro release of said therapeutically active agent when exposed to accelerated storage conditions of one month at 37.degree. C. and 80% relative humidity.