Development of Spray Dried Ritonavir Microparticles for Dissolution Rate Enhancement

Abstract

The purpose of the present investigation was to develop microparticles of Ritonavir to improve its solubility and rate of dissolution and oral bioavailability. Solid dispersions of Ritonavir (BCS-II, anti-HIV drug) with varying contents of Poloxamer 188 were prepared by spray drying technique. The effect of Aerosil 200 on microparticle performance was also investigated. Drug-excipient compatibility and the amorphous state of the drug in microparticles were confirmed by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and x-ray powder diffraction (XRPD) studies, respectively. The surface morphology of microparticles was studied by scanning electron microscopy (SEM). The prepared microparticles were characterized for solubility, drug content, encapsulation efficiency, micromeritic and in-vitro dissolution properties. Use of Poloxamer 188 at an equal ratio with drug resulted in high drug content in microparticles. However, encapsulation efficiency was increased with increase in Poloxamer 188 ratio. FTIR revealed no any chemical changes in drug during spray drying process. Phase transitions and formation of the amorphous state was confirmed by DSC and XRPD studies. SEM photomicrographs showed the formation of uniformly sized Ritonavir microparticles without aggregation in presence of Aerosil 200. However, a strong influence of Poloxamer 188 on solubility and rate of Ritonavir dissolution was observed. In the present research, a spray drying technique was successfully developed for the preparation of free-flowing Ritonavir microparticles exhibiting improved solubility and rate of dissolution and hence, oral bioavailability. The developed technique could be successfully applied for dissolution enhancement of other BCS-II drugs including anti-retroviral drugs.