title: Saturated fatty acids and fatty acid esters promote the polymorphic transition of clarithromycin metastable form I crystal.
abstract: The phase transition of active pharmaceutical ingredients should be taken into account during manufacturing, processing- and storage, because different crystal forms lead to different physical properties of formulations. The phase transition of clarithromycin (CAM) metastable form I to stable form II was investigated on heating with additives such as fatty acids or fatty acid esters. Differential scanning calorimetry analyses revealed that when form I was heated with additives, the phase transition temperature of form I decreased close to the melting points of the additives. Powder X-ray diffraction analyses indicated the tentative presence of a non-crystalline component during the transition of form I to form II on heating with additives. These observations implied that CAM form I dissolved in the melted additives on heating and the dissolved CAM crystallized to form II. Reduction of transition temperatures in the presence of additives were also observed for the crystals of nifedipine form B and carbamazepine form III. These results suggested that the phenomena can be widely applicable for simultaneous crystalline phase transition and granulation using binder additives.
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Miteki
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Mizoguchi
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Aoki
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwao
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan; Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-city, Chiba 274-8510, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Noguchi
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: s-itai@u-shizuoka-ken.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Itai
mesh_terms: D002220:Carbamazepine / Q000737:chemistry; D017291:Clarithromycin / Q000737:chemistry*; D003460:Crystallization; D004952:Esters / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry*; D009543:Nifedipine / Q000737:chemistry; D044367:Phase Transition; D044366:Transition Temperature
chemical_list: D004952:Esters; D005227:Fatty Acids; D002220:Carbamazepine; D017291:Clarithromycin; D009543:Nifedipine
keywords: Clarithromycin; Crystalline phase transition; Differential scanning calorimetry; Melt granulation; Metastable; Powder-X-ray diffraction