Preparation of tadalafil-dapoxetine coamorphous complex with evaluation of dissolution and physical stability
10.16438/j.0513-4870.2018-0260
- VernacularTitle:他达拉非-达泊西汀共无定形物的形成及其溶出度与稳定性的评价
- Author:
Ya-jing SHEN
1
;
Lei QIN
1
;
Wei-li HENG
2
;
Jian-jun ZHANG
2
;
Shuai QIAN
1
;
Yuan GAO
1
Author Information
1. Department of Traditional Chinese Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China
2. Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
tadalafil;
dapoxetine;
coamorphous;
dissolution rate;
physical stability
- From:
Acta Pharmaceutica Sinica
2018;53(7):1162-1168
- CountryChina
- Language:Chinese
-
Abstract:
Tadalafil (TD), a phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, has a low oral bioavailability due to its extremely poorly aqueous solubility. The aim of this study was to enhance its solubility and dissolution by coamorphization with dapoxetine (DP), a selective serotonin reuptake inhibitor to manage premature ejaculation. Coamorphous TD-DP (molar ratio, 1:1) was prepared by solvent-evaporation method and characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR). The supersaturated dissolution of TD from coamorphous TD-DP was investigated in various aqueous media and compared to that of crystalline TD. In addition, physical stability of coamorphous system was also evaluated under the conditions of 40℃/75% relative humidity (RH) and 25℃/60% RH for 90 days. DSC thermogram and PXRD pattern indicated the formation of the coamorphous TD-DP. In comparison to original TD crystal, the dissolution of TD from coamorphous system were significantly enhanced in various media (water, 0.01 mol·L-1 HCl and pH 4.5 phosphate buffer). In addition, no crystallization phenomenon of the prepared coamorphous system was observed until 90 days' storage under 25℃/60% RH. However, when temperature and humidity were increased to 40℃/75% RH, the coamorphous TD-DP was recrystallized easily.
