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

Publication date: 15 January 2017
Source:European Journal of Pharmaceutical Sciences, Volume 97
Author(s): Jin-Seok Choi, Jeong-Sook Park
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±0.16μg/mL with PVP/VA S-630) compared with TDF alone (0.73±0.08μg/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).

Graphical abstract

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