Predictability of drug encapsulation and release from propylene carbonate/PLGA microparticles.

Abstract

Key parameters for microparticle-based parenteral depot formulation development are entrapment efficiency and sustained drug release, which both depend on the intermolecular affinity of the components. Here, partial solubility parameters were evaluated as descriptors for 21 drug substances and 3 polymers in propylene carbonate (PC). Out of these 21 drug substances, eight BCS class II substances (celecoxib, clotrimazole, erythromycin, ibuprofen, indomethacin, itraconazole, lopinavir and ritonavir) were encapsulated using PLGA (Poly(DL-lactide-co-glycolide)) as polymer matrix and PC as a polar aprotic solvent in order to assign microparticle properties to potential affinity-related interactions using partial solubility parameters. Microparticle morphology was highly dependant on the specific glass transition temperature (Tg) of the encapsulated drug substance. A strong correlation (R=0.912) between the encapsulation efficiency and the difference in total solubility parameter (Δδt API-PLGA) underlined the encapsulation predictability. Moreover, in drug release, a significant impact of Δδt API-PLGA on initial burst was observed and even more pronounced on the release rate of the encapsulated drug substance. The possibility to predict these important microparticle properties underline the value of including solubility descriptors such as partial solubility parameters into microparticle formulation development.