Enhancing Solubility and Dissolution Behavior of Finasteride Using Solid Dispersion Technique by Carrier Screening and the New Preparation Instrument.

Purpose: The purpose of this study was to improve the solubility and dissolution rate of finasteride (FIN) by searching for an optimal carrier to prepare the FIN carrier solid dispersions (SDs) and to invent a new solvent evaporation instrument for solid dispersion preparation. Methods: The solubility parameter was first used as a criterion to choose out the optimal carriers for FIN SDs, which has wonderful compatibility between the drug and carrier. Different carriers (hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG 4000), and polyethylene oxide N-60 K (PEO)) were selected with different FIN-to-carrier ratios (1:1, 1:2.5, 1:5, 1:7.5, and 1:10, w/w). The FIN SDs were prepared by a new instrument with the cyclone separation principle which is named cyclone-enhanced nitrogen blower. The prepared SDs were then characterized by solubility, DSC, PXRD, FT-IR, dissolution, cumulative dissolution velocity, and stability studies. Results: The results of solubility parameters and kinetic solubility were consistent. All three FIN SDs were successfully synthesized by the new method of nitrogen-blowing solvent evaporation with cyclone enhancement. FT-IR revealed significant intermolecular interactions which are formed by hydrogen bonds between the amide group on ring A of FIN and the hydroxyl group of HPMC. PXRD and DSC analysis indicated that the morphological structure of the FIN was converted into an amorphous or a molecular solution state and lost its original crystallographic structure when FIN was combined with dispersion carriers. The SDs prepared using the new method exhibited good stability, as demonstrated by the stability studies. Furthermore, the FIN-HPMC solid dispersion system in a mass ratio of 1:5 showed the best improvement in solubility and dissolution rate. Conclusions: The solid dispersion system of FIN and HPMC in a mass ratio of 1:5 was the most promising combination to improve dissolution among all tested systems. Moreover, the new instrument of cyclone-enhanced nitrogen blower is an effective and high-throughput way for the preparation of SDs. [ABSTRACT FROM AUTHOR]