title: A high throughput platform for understanding the influence of excipients on physical and chemical stability.
abstract: The present study puts forward a miniaturized high-throughput platform to understand influence of excipient selection and processing on the stability of a given drug compound. Four model drugs (sodium naproxen, theophylline, amlodipine besylate and nitrofurantoin) and ten different excipients were selected. Binary physical mixtures of drug and excipient were transferred to a 96-well plate followed by addition of water to simulate aqueous granulation environment. The plate was subjected for XRPD measurements followed by drying and subsequent XRPD and HPLC measurements of the dried samples. Excipients with different water sorbing potential were found to influence distinctly on the phase transformation behaviour of each drug. Moreover, the amount of water addition was also a critical factor affecting phase transformation behaviour. HPLC analysis revealed one of the drug:excipient pairs with a tendency for chemical degradation. The proposed high-throughput platform can be used during early drug development to simulate typical processing induced stress in a small scale and to understand possible phase transformation behaviour and influence of excipients on this.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Dhara
authors.initials: D
authors.lastname: Raijada
authors.forename: Claus
authors.initials: C
authors.lastname: Cornett
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
mesh_terms: D017311:Amlodipine / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D009288:Naproxen / Q000737:chemistry*; D009582:Nitrofurantoin / Q000737:chemistry*; D033362:Powder Diffraction; D013806:Theophylline / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D005079:Excipients; D014867:Water; D017311:Amlodipine; D009288:Naproxen; D009582:Nitrofurantoin; D013806:Theophylline