Method of preparation of mixed phase co-crystals with active agents
This invention pertains to a method of preparing mixed phase co-crystals of active agents with one or more materials that allows the modification of the active agent to a new physical/crystal form with unique properties useful for the delivery of the active agent, as well as compositions comprising the mixed phase co-crystals.
1. A method of preparing mixed phase co-crystal composition consisting of the steps of:
(a) forming a first solution of progesterone, hydroxypropyl methylcellulose, and polyoxamer 188 dissolved in ethanol;
(b) mixing water with the first solution to form a second solution;
(c) mixing or allowing the second solution to stand for a sufficient period of time to form an initial kinetically favored meta-stable crystalline phase in the second solution,
(d) forming the thermodynamically favored mixed phase co-crystal composition from the meta-stable crystalline phase by allowing the initial meta-stable crystalline phase to stand or by mixing of the initial meta-stable crystalline phase,
(e) optionally, isolating the mixed phase co-crystal composition,
(f) optionally, washing the mixed phase co-crystal composition, and
(g) optionally, drying the mixed phase co-crystal composition,
wherein the progesterone, hydroxypropyl methylcellulose, and polyoxamer 188 are contained within the mixed phase co-crystal composition.