title: Modeling the deagglomeration of micronized benzodiazepines from powder mixtures added to dissolution media.
abstract: The objective of this research was to model benzodiazepine deagglomeration profiles of percent agglomerated versus time when interactive mixtures containing micronized benzodiazepines were added to water. Micronized diazepam, nitrazepam, oxazepam, and, for ternary mixtures, micronized sodium lauryl sulfate were mixed with lactose-povidone granules (250-355 microm). After rapid dissolution of the lactose granules, bimodal particle size distributions of benzodiazepines, determined by laser diffraction particle sizing, represented dispersed and agglomerated distributions. The concentrations of agglomerated particle decreased with time and approached constant values. Deagglomeration profiles were determined and best modeled by a three-parameter single-exponential decay equation. A nonlinear least-squares approach was used to estimate the concentration of dispersible (C(0)) and nondispersible agglomerates (C(0a)) and the deagglomeration rate constant (K(a)). Increasing benzodiazepine and sodium lauryl sulphate concentrations in the lactose-povidone mixtures increased both dispersible and nondispersible agglomerate concentrations. Deagglomeration rate was relatively fast with half-lives around 15 min. The estimated parameters of C(0a) and K(a) may provide useful information in optimizing the design of formulations of poorly water soluble, micronized drugs to maximize their dispersion.
authors.affiliation: Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Feng-Ying
authors.initials: FY
authors.lastname: Zhao
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Stewart
mesh_terms: D001569:Benzodiazepines / Q000032:analysis* / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D008956:Models, Chemical; D011208:Powders; D012995:Solubility
chemical_list: D011208:Powders; D001569:Benzodiazepines