title: Design of PVP/VA S-630 based tadalafil solid dispersion to enhance the dissolution rate.
abstract: 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).
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea.
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea. Electronic address: eicosa@cnu.ac.kr.
authors.forename: Jeong-Sook
authors.initials: JS
authors.lastname: Park
mesh_terms: D004339:Drug Compounding; D015195:Drug Design; D011759:Pyrrolidines / Q000138:chemical synthesis*; D012995:Solubility; D000068581:Tadalafil / Q000138:chemical synthesis*; D014665:Vasodilator Agents / Q000138:chemical synthesis*; D014753:Vinyl Compounds / Q000138:chemical synthesis*; D014961:X-Ray Diffraction
chemical_list: D011759:Pyrrolidines; D014665:Vasodilator Agents; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D000068581:Tadalafil
keywords: In vitro dissolution rate; Meglumine; Solid dispersion (SD); Solubilizer; Stability; Tadalafil (TDF)