title: Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments.
abstract: Hydrate formation is a phase transition which can occur during manufacturing processes involving water. This work considers the prevention of hydration of anhydrous olanzapine and hydrate conversions in the presence of water and polymers (polyethyleneglycol; hydroxypropylcellulose; polyvinylpyrrolidone) in forming pellets by wet extrusion and spheronisation. Anhydrous olanzapine was added to water with or without those polymers prior to extrusion with microcrystalline cellulose. Assessment of olanzapine conversion was made by XRP-Diffraction; FTIR spectroscopy; calorimetry (DSC) and microscopy (SEM for crystal size and shape). The addition of water converted the anhydrous form into dihydrate B and higher hydrate; whereas polyethyleneglycol promoted a selective hydrate conversion into the higher hydrate olanzapine form. Both polyvinylpyrrolidone and hydroxypropylcellulose prevented the hydrate transformations of the anhydrous drug; the latter even in the presence of hydrate seeds. This may be explained by the higher H-bond ability; higher network association and higher hydrophobicity of hydroxypropylcellulose by comparison with polyethyleneglycol and polyvinylpyrrolidone; which could contribute to its higher affinity to the crystal surfaces of the hydrate nuclei/initial crystals and promoting steric hindrance to the incorporation of other drug molecules into the crystal lattice; thus, preventing the crystal growth. The addition of microcrystalline cellulose needed for the pellets production (final product) did not eliminate the protector effect of both hydroxypropylcellulose and polyvinylpyrrolidone during pellets' processing and dissolution evaluation.
authors.affiliation: iMed.ULisboa, Departamento de Farmácia Galénica e Tecnologia Farmacêutica, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, P-1649-003 Lisboa, Portugal. mdcpaisana@gmail.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Paisana
authors.affiliation: Institut für Pharmazeutische Technologie und Biopharmazie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, D-72076 Tübingen, Germany. Martin.Wahl@uni-tuebingen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Wahl
authors.affiliation: iMed.ULisboa, Departamento de Farmácia Galénica e Tecnologia Farmacêutica, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, P-1649-003 Lisboa, Portugal. jfpinto@ff.ul.pt.
authors.forename: João
authors.initials: J
authors.lastname: Pinto
mesh_terms: D001569:Benzodiazepines / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D000077152:Olanzapine; D044367:Phase Transition; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D005079:Excipients; D011108:Polymers; D014867:Water; D001569:Benzodiazepines; D002482:Cellulose; C008079:hydroxypropylcellulose; D011205:Povidone; D000077152:Olanzapine; C109691:microcrystalline cellulose
keywords: anhydrous; extrusion; hydrate; hydroxypropylcellulose; olanzapine; pellet; polyethyleneglycol; polymorphism; polyvinylpyrrolidone; spheronisation