title: The influence of amorphization methods on the apparent solubility and dissolution rate of tadalafil.
abstract: This study for the first time investigates the solubility and dissolution rate of amorphous tadalafil (Td)--a poorly water soluble chemical compound which is commonly used for treating the erectile dysfunction. To convert the crystalline form of Td drug to its amorphous counterpart we have employed most of the commercially available amorphization techniques i.e. vitrification, cryogenic grinding, ball milling, spray drying, freeze drying and antisolvent precipitation. Among the mentioned methods only quenched cooling of the molten sample was found to be an inappropriate method of Td amorphization. This is due to the thermal decomposition of Td above 200°C, as proved by the thermogravimetric analysis (TGA). Disordered character of all examined samples was confirmed using differential scanning calorimetry (DSC) and X-ray powder diffraction (PXRD). In the case of most amorphous powders, the largest 3-fold increase of apparent solubility was observed after 5 min, indicating their fast recrystallization in water. On the other hand, the partially amorphous precipitate of Td and hypromellose enhanced the solubility of Td approximately 14 times, as compared with a crystalline substance, which remained constant for half an hour. Finally, disk intrinsic dissolution rate (DIDR) of amorphous forms of Td was also examined.
authors.affiliation: Medical University of Gdansk, Department of Physical Chemistry, Hallera 107, 80-416 Gdansk, Poland. Electronic address: kamil.wlodarski@gumed.edu.pl.
authors.forename: K
authors.initials: K
authors.lastname: Wlodarski
authors.affiliation: Medical University of Gdansk, Department of Physical Chemistry, Hallera 107, 80-416 Gdansk, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Sawicki
authors.affiliation: Trinity College Dublin, School of Pharmacy and Pharmaceutical Sciences, College Green, Dublin 2, Ireland.
authors.forename: K J
authors.initials: KJ
authors.lastname: Paluch
authors.affiliation: Trinity College Dublin, School of Pharmacy and Pharmaceutical Sciences, College Green, Dublin 2, Ireland.
authors.forename: L
authors.initials: L
authors.lastname: Tajber
authors.affiliation: Medical University of Gdansk, Department of Food Science, Hallera 107, 80-416 Gdansk, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Grembecka
authors.affiliation: Institute of Non Ferrous Metals, Sowinskiego 5, 44-100 Gliwice, Poland.
authors.forename: L
authors.initials: L
authors.lastname: Hawelek
authors.affiliation: University of Silesia, Institute of Physics, Uniwersytecka 4, 40-007 Katowice, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Wojnarowska
authors.affiliation: University of Silesia, Institute of Physics, Uniwersytecka 4, 40-007 Katowice, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Grzybowska
authors.affiliation: University of Silesia, Institute of Physics, Uniwersytecka 4, 40-007 Katowice, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Talik
authors.affiliation: University of Silesia, Institute of Physics, Uniwersytecka 4, 40-007 Katowice, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Paluch
mesh_terms: D002152:Calorimetry, Differential Scanning; D002243:Carbolines / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D065546:Drug Liberation; D058986:Phosphodiesterase 5 Inhibitors / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D000068581:Tadalafil; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil
keywords: Amorphous drugs; Apparent solubility; Dissolution rate; Precipitation from solution; Tadalafil