title: The effect of surfactants on the dissolution behavior of amorphous formulations.
abstract: The optimal design of oral amorphous formulations benefits from the use of excipients to maintain drug supersaturation and thus ensures adequate absorption during intestinal transit. The use of surfactants for the maintenance of supersaturation in amorphous formulations has not been investigated in detail. The main aim of this study was to investigate the effect of surfactant on the dissolution behavior of neat amorphous drug and binary polymer based solid dispersion. Indomethacin was used as the model drug and the surfactants studied were polysorbate 80 and poloxamer 407. The presence of surfactants (alone or in combination with polymers) in the buffer was detrimental to the dissolution of neat amorphous indomethacin, suggesting that the surfactants promoted the crystallization of neat amorphous indomethacin. In contrast, the presence of surfactants (0.01% w/v) in the buffer resulted in a significant improvement on the dissolution behavior of binary polymer based solid dispersion. Incorporating the surfactant to the formulation to form ternary solid dispersion adversely affected the dissolution behavior. In conclusion, the use of surfactants (as wetting or solubilization agents) in dissolution studies of neat amorphous drugs requires prudent consideration. The design of amorphous formulations with optimal dissolution performance requires the appropriate selection of a combination of excipients and consideration of the method of introducing the excipients.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand; Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Finland.
authors.forename: Pei T
authors.initials: PT
authors.lastname: Mah
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Finland.
authors.forename: Dunja
authors.initials: D
authors.lastname: Novakovic
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Finland. Electronic address: clare.strachan@helsinki.fi.
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Strachan
authors.affiliation: Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Laaksonen
mesh_terms: D003460:Crystallization; D007213:Indomethacin / Q000737:chemistry; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013501:Surface-Active Agents / Q000494:pharmacology*
chemical_list: D013501:Surface-Active Agents; D007213:Indomethacin
keywords: Amorphous; Crystallization; Dissolution; Indomethacin; Polymer; Solid dispersion; Supersaturation; Surfactant