(106b) Simultaneous Microparticle Formation and Mixing in Supercritical CO2. Fast-Release Navirapine Drug Formulation

Purpose: To prepare microparticles of poorly water soluble model drug, nevirapine (NEV) and simultaneously prevent the particle aggregation using excipients by supercritical fluid antisolvent (SAS) process in a single step.

Method: Microparticles of NEV were prepared by SAS method and simultaneously deposited the drug at various ratios (0, 10, 21, 37, 51 and 100 wt. %) on the surface of excipients such as lactose and microcrystalline cellulose (MCC) and their mixture (1:1 ratio) in a single step process. This is achieved by precipitation of drug particles in high pressure stirred bed vessel containing excipient particles using SAS method. These mixtures were characterized for surface morphology by scanning electron microscopy (SEM), crystallinity by X-ray diffraction (XRD), physicochemical interactions of drug ? excipient mixture by differential scanning calorimetry (DSC) and Fourier transform-infrared spectroscopy (FT-IR). The drug content uniformity and dissolution of NEV from lactose and MCC blends were determined.

Results: The SAS method produced microparticles of NEV and deposited on lactose and MCC to produce a highly interactive mixture of drug and the carrier. The drug particle aggregation was able to effectively overcome when the drug was deposited on the surface of lactose or MCC by SAS process as evidenced from SEM studies. The XRD results indicate that the crystallinity of NEV was not affected due to SAS treatment and DSC and IR studies reveal that the physico-chemical properties of the drug was not significantly affected by SAS treatment. The SAS produced drug microparticles with lactose and / or MCC produced significantly faster drug dissolution rate as compared to SAS drug alone or physical mixtures of SAS produced drug and excipients.

Conclusion: Micronization of NEV and particle de-aggregation with lactose and MCC by SAS process was achieved in a single step. A high dissolution rate of NEV was achieved due to formation of interactive mixture with lactose and / or MCC.