Controlled release aqueous emulsion

A controlled release pharmaceutical composition that comprises an oil-in-water emulsion including a water phase and an oil phase, said emulsion being stable at a pH value of about 5.5 to about 7.5 but separating at a pH value less than about 2.0 into water and oil phases, said composition having an average oil phase particle size of about 100 nm to about 250 nm, a pH value of about 5.5 to about 7.5 and a viscosity at 20.degree.-25.degree. of about 1 to about 200 cps, said water phase constituting at least 50 weight percent of the total composition, said oil phase comprising a wax having a melting point of about 45.degree. to about 70.degree. C. and present in an amount of about 5 to about 20 weight percent of the total composition, said wax having dissolved or dispersed therein a pharmaceutically effective amount of a pharmacologically active compound that is free from decomposition at a temperature below about 90.degree. C., said oil and water phases being emulsified by an emulsifier present in a total amount of about 2 to about 20 weight percent of the total composition that comprises 0.5 to about 20 weight percent of the total composition phospholipid and zero to about 3 weight percent of the total composition of a non-ionic surfactant having an HLB of about 8 to about 16, said composition containing zero to about 10 weight percent of the total composition additional excipient.

A process for preparing a controlled release oil-in-water emulsion pharmaceutical composition, said emulsion being stable at a pH value of about 5.5 to about 7.5 but separating at a pH value of less than about 2.0 into water and oil phases that comprises the steps of:

• (a) providing a homogeneous molten admixture at a temperature below about 85.degree. C., said molten admixture containing (i) wax matrix having dissolved or dispersed therein (ii) a pharmaceutically effective amount of a pharmacologically active compound and (iii) a phospholipid emulsifier, said matrix being a wax having a melting point of about 40.degree. C. to about 80.degree. C., said pharmacologically active compound being free from decomposition below about 90.degree. C., the ratio of said wax matrix to said emulsifier being about 1:1 to about 5:1;
• (b) providing an aqueous phase at a temperature about 5.degree. C. higher than that of said molten admixture;
• (c) microemulsifying said molten admixture as oil phase with a sufficient amount of said aqueous phase at the temperature of said aqueous phase is external, in which the average oil phase particle size is about 100 nm to about 250 nm, and in which the relative amounts of aqueous and oil phases are within about 20 percent of the final percentages desired for those phases;
• (d) cooling the resultant emulsion to a temperature of about 10.degree. to about 40.degree. C.;
• and
• (e) admixing zero to about 10 weight percent of the total composition additional excipient, sufficient water and adjusting the pH value such that the formed pharmaceutical composition has a viscosity at 20.degree.-25.degree. C. of about 1 to about 1000 cps, a pH value of about 4.5 to about 8.0, a water phase that constitutes at least 25 weight percent of the total composition, an oil phase that contains (i) the wax matrix constituting about 3 to about 30 weight percent of the total composition, (ii) the emulsifier constituting about 2 to about 20 weight percent of the total composition, and (iii) the pharmacologically active compound.