title: Design and characterization of a surfactant-enriched tablet formulation for oral delivery of a poorly water-soluble immunosuppressive agent.
abstract: The feasibility of incorporating significant quantities of the anionic surfactant, sodium lauryl sulfate (SDS), into an immediate release tablet formulation of a poorly water-soluble immunosuppressive agent was investigated. Despite the extremely poor compressibility of SDS and poor chemical stability of the drug, a commercializable, direct-compression tablet formulation with satisfactory mechanical properties and acceptable chemical stability was achieved. Optimal in vitro release of the drug from the tablet formulation was achieved by establishing the minimum molar uptake ratio necessary to achieve complete micellar solubilization of the drug, after which formulation studies were conducted to determine the influence of formulation and process variables on the rate and extent of drug release. A model-independent analysis of dissolution results in a reduced volume (250 ml) of modified simulated gastric fluid demonstrated that the rate and extent of drug release was highly dependent on the mean particle size of the bulk drug, but independent of compression force above that required to achieve a compact of acceptable mechanical strength. Employing the Korsmeyer-Peppas model of Fickian and non-Fickian drug release, it was further shown that release of the drug from the dosage form was governed largely by surface erosion of the surfactant-enriched tablet matrix.
authors.affiliation: Department of Pharmaceutical Research, Merck Research Laboratories, Merck & Co., Inc., WP78A-31, P.O. Box 4, West Point, PA 19486, USA. stephen_ruddy@merck.com
authors.forename: S B
authors.initials: SB
authors.lastname: Ruddy
authors.forename: B K
authors.initials: BK
authors.lastname: Matuszewska
authors.forename: Y A
authors.initials: YA
authors.lastname: Grim
authors.forename: D
authors.initials: D
authors.lastname: Ostovic
authors.forename: D E
authors.initials: DE
authors.lastname: Storey
mesh_terms: D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D007093:Imidazoles / Q000008:administration & dosage* / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D010316:Particle Size; D012967:Sodium Dodecyl Sulfate / Q000008:administration & dosage*; D012995:Solubility; D013501:Surface-Active Agents / Q000008:administration & dosage*; D013607:Tablets; D016559:Tacrolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D007093:Imidazoles; D007166:Immunosuppressive Agents; C116704:L 733725; D013501:Surface-Active Agents; D013607:Tablets; D012967:Sodium Dodecyl Sulfate; D016559:Tacrolimus