PVP/corticosteroid microspheres produced by supercritical antisolvent coprecipitation

Abstract

Coprecipitation of poorly water soluble drugs with an hydrophilic polymer can enhance the drug dissolution rate and, therefore, its bioavailability. In this work, supercritical antisolvent (SAS) precipitation is proposed for the coprecipitation of corticosteroids. This class of compounds cannot be directly processed by SAS, since it precipitates in form of large crystals. Dexamethasone (DMS), prednisolone (PDN) and budesonide (BDS) were tested. To control microspheres size and morphology, the effect of polymer/drug ratio, precipitation pressure and concentration were investigated.For all the processed systems polyvinylpyrrolidone (PVP)/corticosteroids, spherical microparticles were obtained at selected operating conditions and at proper PVP/corticosteroid ratios. Particles mean diameter ranged between about 1.8 and 2.5μm for PVP/DMS, 2.0–3.1μm for PVP/PDN and 3.0–3.6μm for PVP/BDS. All precipitates were characterized, to determine the effective drug entrapment efficiency and drug release rate. The performed analyses showed that the drug entrapment efficiency was about 90–95% with respect to the initial concentration in all samples. The drug dissolution rate in phosphate buffered saline solution (PBS) was largely improved: it was more than 4 times faster than the one of unprocessed drug in the case of DMS and about 5 times faster in the case of PDN and BDS.