title: Deaggregation during the dissolution of benzodiazepines in interactive mixtures.
abstract: The purpose of this research was to investigate the influence of surfactants on the dissolution of benzodiazepines in interactive mixtures. The dissolution of ternary interactive mixtures consisting of micronized drugs (oxazepam, nitrazepam, and flunitrazepam) and micronized surfactants (sodium lauryl sulfate and cetrimide) adhered onto the surface of a lactose carrier (250-355 microm) was studied using the USP/NF paddle method. Dissolution was considered to occur from dispersed particle and aggregate fractions of the drugs, and data were modeled using multiexponential equations. The initial concentrations of the aggregates and dissolution rate constants were estimated using a Marquardt-Levenberg nonlinear least squares algorithm. The marked increase in dissolution rate which occurred with increasing concentrations of sodium lauryl sulfate and cetrimide resulted both from deaggregation of the benzodiazepine particles and from increases in the dissolution rate constants of the dispersed particle and aggregate fractions probably associated with an increased intrinsic dissolution rate. The presence of 5% sodium lauryl sulfate in the interactive mixture reduced the initial percent of aggregates from about 85% in a binary mixture to less than 10% and about doubled the dispersed particle dissolution rate constant. The presence of the surfactant in the surface particulate matrix of the interactive mixture was essential for its deaggregation effect. Sodium lauryl sulfate was more effective than cetrimide in achieving drug deaggregation.
authors: Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, Parkville, Australia.
authors: J
authors: J
authors: Liu
authors: P J
authors: PJ
authors: Stewart
mesh_terms: D000268:Adhesiveness; D001569:Benzodiazepines / Q000737:chemistry*; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D005445:Flunitrazepam / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D009567:Nitrazepam / Q000737:chemistry; D010076:Oxazepam / Q000737:chemistry; D010316:Particle Size; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013501:Surface-Active Agents / Q000494:pharmacology*
chemical_list: D002593:Cetrimonium Compounds; D003902:Detergents; D013501:Surface-Active Agents; D001569:Benzodiazepines; D012967:Sodium Dodecyl Sulfate; D005445:Flunitrazepam; D010076:Oxazepam; D009567:Nitrazepam; D007785:Lactose; D000077286:Cetrimonium