title: Why sildenafil and sildenafil citrate monohydrate crystals are not stable?
abstract: Sildenafil citrate was crystallized by various techniques aiming to determine the behavior and factors affecting the crystal growth. There are only 2 types of sildenafil obtaining from crystallization: sildenafil (1) and sildenafil citrate monohydrate (2). The used techniques were (i) crystallization from saturated solutions, (ii) addition of an antisolvent, (iii) reflux and (iv) slow solvent evaporation method. By pursuing these various methods, our work pointed that the best formation of crystal (1) was obtained from technique no. (i). Surprisingly, the obtained crystals (1) were perfected if the process was an acidic pH at a cold temperature then perfect crystals occurred within a day. Crystals of compound (2) grew easily using technique no. (ii) which are various polar solvents over a wide range of pH and temperature preparation processes. The infrared spectroscopy and nuclear magnetic resonance spectra fit well with these two X-ray crystal structures. The crystal structures of sildenafil free base and salt forms were different from their different growing conditions leading to stability difference.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand ; Drug and Cosmetic Research and Development Group, School of Pharmacy, Walailak University, Thasala, Nakhonsithammarat 80161, Thailand.
authors.forename: Somchai
authors.initials: S
authors.lastname: Sawatdee
authors.affiliation: Faculty of Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
authors.forename: Chaveng
authors.initials: C
authors.lastname: Pakawatchai
authors.affiliation: Inorganic and Materials Chemistry Research Unit, Department of Chemistry, Faculty of Science, Thaksin University, Songkhla 90000, Thailand.
authors.forename: Kwanjai
authors.initials: K
authors.lastname: Nitichai
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand ; Nanotec-PSU Excellence Center on Drug Delivery System, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
authors.forename: Teerapol
authors.initials: T
authors.lastname: Srichana
authors.affiliation: Inorganic and Materials Chemistry Research Unit, Department of Chemistry, Faculty of Science, Thaksin University, Songkhla 90000, Thailand.
authors.forename: Hirihattaya
authors.initials: H
authors.lastname: Phetmung
keywords: Antisolvent addition; Sildenafil; Sildenafil citrate monohydrate; Slow solvent evaporation; Solution crystallization; Stability