title: Effect of polymer microstructure on the docetaxel release and stability of polyurethane formulation.
abstract: PurSil®AL20 (PUS), a copolymer of 4,4'-dicyclohexylmethane diisocyanate (HMDI), 1,4-butane diol (BD), poly-tetramethylene oxide (PTMO) and poly-dimethyl siloxane (PDMS) was investigated for stability as a vehicle for Docetaxel (DTX) delivery through oesophageal drug eluting stent (DES). On exposure to stability test conditions, it was found that DTX release rate declined at 4 and 40 °C. In order to divulge reasons underlying this, changes in DTX solid state as well as PUS microstructure were followed. It was found that re-crystallization of DTX in PDMS rich regions was reducing the drug release at both 4 °C and 40 °C samples. So far microstructural features have not been correlated with stability and drug release, and in this study we found that at 40 °C increase in microstructural domain sizes and the inter-domain distances (from ∼85 Å to 129 Å) were responsible for hindering the DTX release in addition to DTX re-crystallization.
authors.affiliation: Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Mohsin
authors.initials: M
authors.lastname: Shaikh
authors.affiliation: Ian Wark Research Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes, SA 5095, Australia.
authors.forename: Namita Roy
authors.initials: NR
authors.lastname: Choudhury
authors.affiliation: ANSTO, Locked Bag 2001, Kirrawee, NSW 2232, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Knott
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research, Centre for Molecular and Medical Research, School of Medicine, Faculty of Health, Deakin University, Pigdons Road, Waurn Ponds, Geelong, Victoria 3216, Australia.
authors.forename: Jagat Rakesh
authors.initials: JR
authors.lastname: Kanwar
authors.affiliation: Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia. Electronic address: Sanjay.garg@unisa.edu.au.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Garg
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D054855:Drug-Eluting Stents; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011140:Polyurethanes / Q000737:chemistry*; D043823:Taxoids / Q000737:chemistry*; D013696:Temperature
chemical_list: D011108:Polymers; D011140:Polyurethanes; D043823:Taxoids; D000077143:Docetaxel
keywords: Docetaxel; Drug release; Polymer microstructure; Polyurethane; Small-angle X-ray diffraction; Stability