Mechanistic Study of HPMC-Prolonged Supersaturation of Hydrocortisone

Supersaturation formulation is an effective way to improve the oral bioavailability of poorly water-soluble drugs, and water-soluble polymers are commonly used to prolong the supersaturation. However, the mechanism for such supersaturation prolonging effect is not clearly understood. Using the hydrocortisone/hydroxypropyl methylcellulose (HPMC) pair as a model system, we found that HPMC prolongs hydrocortisone supersaturation by inducing the formation of a metastable crystal polymorph of higher solubility, hence lowering the actual supersaturation level in the solution. A possible mechanism is proposed to explain the selective polymorph formation in the presence of polymers.