Amorphous Solid Dispersion Formation via Solvent Granulation – A Case Study with Ritonavir and Lopinavir

With an increase in the number of therapeutically active compounds exhibiting low water solubility, formulation strategies such as amorphization, salt formation, complexation, micellization, are increasingly employed to improve solubility and bioavailability. Among these, amorphous formulations, which typically yield a higher solubility (supersaturated solution) and dissolution rate as compared to the crystalline state are often a preferred strategy.

Abstract

Herein, we evaluate the potential of using a simple solvent granulation process to prepare a binary drug amorphous solid dispersion (ASD) containing two anti-HIV drugs, ritonavir and lopinavir. The drugs were granulated onto a mixture of lactose and microcrystalline cellulose, followed by drying to remove the solvent.

The resultant granules were characterized and each drug was found to be X-ray amorphous. No crystallization was observed following storage for 1 month under accelerated stability conditions (40°C and 75% relative humidity). The dissolution behavior of the compacted granules was compared with the marketed formulation.

The dissolution rate of ritonavir was found to be significantly retarded relative to the commercial product when the two drugs were co-granulated. However, comparable release could be achieved when each drug was individually granulated, followed by combination and compaction. The solvent granulation approach may be a viable method to make ASDs of low dose drugs with low crystallization tendencies.

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