Design of PVP/VA S-630 based tadalafil solid dispersion to enhance the dissolution rate

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• 作者：Jin-Seok Choi ; Jeong-Sook Park ; ^{eicosa@cnu.ac.kr}
• 关键词：TDF ; Tadalafil ; SD ; Solid dispersion ; DW ; Distilled water ; FE-SEM ; Field emission scanning electron microscope ; DSC ; Differential scanning calorimetry ; PXRD ; Powder X-ray diffraction ; SLS ; Sodium lauryl sulfate
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：97
• 期：Complete
• 页码：269-276
• 全文大小：1034 K
• 卷排序：97

文摘

Tadalafil (TDF) is a Biopharmaceutics Classification System (BCS) class II drug; the efficacy thereof is critically limited by inherent poor water solubility. Solid dispersion (SD) techniques are widely used to improve the bioavailability of drugs that are poorly water-soluble. Herein, we used an SD technique to improve the solubility and in vitro dissolution rate of TDF; a solvent evaporation method was applied involving the use of hydrophilic carriers (PVP/VA S-630) and assistants (malic acid or meglumine). The TDF-SD formulations were evaluated in terms of the solubility, in vitro dissolution, and stability. Physical properties were confirmed by field-emission scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy (FT-IR). TDF-SD formulations containing assistants (malic acid or meglumine) and various solubilizers exhibited significantly enhanced solubility in distilled water (DW) (up to 27.3-fold; 18.5 ± 0.16 μg/mL with PVP/VA S-630) compared with TDF alone (0.73 ± 0.08 μg/mL). However, the dissolution rate of malic acid based formulation was decreased as the PVP/VA S-630 content increased compared to meglumine based formulation. Thus, the optimal TDF-SD formulation (TDF/meglumine/PVP/VA S-630/Aerosil 200: 1/3/5/3) exhibited a greater dissolution rate (89.1 ± 3.9%) than TDF alone (6.2 ± 2.5%) and Cialis® powder (16.0 ± 1.9%) in DW. The final TDF-SD formulation was amorphous in nature and exhibited good stability. In conclusion, TDF-SD was successfully improved in vitro dissolution rate of TDF compared to commercial products (Cialis®) in the dissolution media without sodium lauryl sulfate (SLS).