title: Amorphous Sulfadoxine: A Physical Stability and Crystallization Kinetics Study.
abstract: Poor aqueous solubility of drugs and the improvement thereof has always been a challenge for the pharmaceutical industry. With this, one of the focuses of the pharmaceutical research scientist involves investigating possible metastable forms of a given drug to be incorporated into solid dosage forms. The rationale being, the improved solubility offered by the metastable solid-state forms of drugs. Solubility remains a major challenge for formulation scientists, especially with antimicrobial agents where the emergence of resistance is directly dependent on the concentration and duration of the parasite exposed to the drug. Sulfadoxine-pyrimethamine combination therapies are still the recommended treatments for uncomplicated Plasmodium falciparum malaria. The aim of this study was to prepare an amorphous form of sulfadoxine and to investigate the stability and recrystallization behavior thereof. The amorphous form was prepared by the well-known quench cooling of the melt. The physico-chemical properties and stability of amorphous sulfadoxine were studied using hot-stage microscopy (HSM), scanning electron microscopy (SEM), x-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), as well as microcalorimetry. The recrystallization kinetics were studied isothermally by applying the Johnson-Mehl-Avrami model and non-isothermally by applying the Kissinger model. The physical stabilization of the amorphous form was investigated using physical mixtures of amorphous sulfadoxine with polyvinylpyrrolidone-25 (PVP-25). It was proved that sulfadoxine is a good glass former with relative high physical stability; however, water acts as a strong plasticizer for amorphous sulfadoxine, detrimentally affecting the stability during exposure to high moisture conditions.
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, Potchefstroom Campus, North-West University, 2520, Potchefstroom, South Africa. marique.aucamp@nwu.ac.za.
authors.forename: Marique
authors.initials: M
authors.lastname: Aucamp
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, Potchefstroom Campus, North-West University, 2520, Potchefstroom, South Africa.
authors.forename: Marnus
authors.initials: M
authors.lastname: Milne
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, Potchefstroom Campus, North-West University, 2520, Potchefstroom, South Africa.
authors.forename: Wilna
authors.initials: W
authors.lastname: Liebenberg
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004338:Drug Combinations; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D007700:Kinetics; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008956:Models, Chemical; D011108:Polymers / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D011739:Pyrimethamine / Q000737:chemistry; D012995:Solubility; D013413:Sulfadoxine / Q000737:chemistry*; D013696:Temperature; D014867:Water / Q000737:chemistry; D014965:X-Rays
chemical_list: D004338:Drug Combinations; D011108:Polymers; D011208:Powders; D014867:Water; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011205:Povidone; D011739:Pyrimethamine
keywords: amorphous; crystallization kinetics; stability; sulfadoxine