title: High-throughput study of phenytoin solid dispersions: formulation using an automated solvent casting method, dissolution testing, and scaling-up.
abstract: A high-throughput experimentation method for studying the dissolution of phenytoin, a poorly water soluble drug, was developed and validated. Solid dispersions with 12 excipients (7 polymers and 5 surfactants) were prepared and tested. Each excipient was screened with three drug loadings: 10, 20, and 40% (w/w). Each solid dispersion was prepared in triplicate, for a total of 108 samples. The drug dissolution was studied in simulated gastric fluid without pepsin plus 1% sodium laurylsulfate. This study led to the identification of three improved formulations, exhibiting an extent of dissolution higher than 90% after both 30 and 60 min. The HTE results could be reproduced at a larger scale using a conventional solvent evaporating method, proving the reliability of the HTE protocol.
authors.affiliation: Laboratory for Pharmacotechnology and Biopharmacy, K.U. Leuven, Gasthuisberg O&N2, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Valéry
authors.initials: V
authors.lastname: Barillaro
authors.forename: Paolo P
authors.initials: PP
authors.lastname: Pescarmona
authors.forename: Michiel
authors.initials: M
authors.lastname: Van Speybroeck
authors.forename: Thao Do
authors.initials: TD
authors.lastname: Thi
authors.forename: Jan
authors.initials: J
authors.lastname: Van Humbeeck
authors.forename: Jan
authors.initials: J
authors.lastname: Vermant
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.forename: Johan A
authors.initials: JA
authors.lastname: Martens
authors.forename: Guy
authors.initials: G
authors.lastname: Van Den Mooter
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000737:chemistry; D001331:Automation / Q000379:methods*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D005750:Gastric Juice / Q000737:chemistry; D010672:Phenytoin / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D005079:Excipients; D011108:Polymers; D012997:Solvents; D013501:Surface-Active Agents; D010672:Phenytoin