title: Drug solubility effects on predicting optimum conditions for extrusion and spheronization of pellets.
abstract: This paper explores the utility of aqueous solubility of structurally similar drugs in predicting optimum conditions for extrusion and spheronization of pellets using response surface methodology. Pharmacologically active xanthine derivatives exhibiting widely varying aqueous solubility were used to determine optimum conditions for pelletization. The amount of water added to the formulation, wet mixing time, and spheronizing time were explored in a series of central composite experimental designs to exhaustively explore and mathematically model the response surfaces for each drug. Using a marketed microcrystalline cellulose excipient, optimum extrusion and spheronization conditions for less soluble drugs required more water, a longer wet mixing time, and prolonged spheronizing times. Results were similar when a new microcrystalline cellulose was substituted, except that more water was required. When comparing results for different drugs, a strong linear relationship was observed between the aqueous solubility of the drug and the water content required for optimum pellet production. The water content range over which quality pellets could be produced was much broader for poorly soluble drugs. Aqueous solubility of the active component appears to be a good predictor for the water requirements for optimum extrusion and spheronization of pellets for pharmaceutical applications.
authors.affiliation: Hoechst Marion Roussel, Inc., Kansas City, Missouri 64134-0627, USA. greghileman@kcexgconn1.kc.mmd.com
authors.forename: G A
authors.initials: GA
authors.lastname: Hileman
authors.forename: S M
authors.initials: SM
authors.lastname: Upadrashta
authors.forename: S H
authors.initials: SH
authors.lastname: Neau
mesh_terms: D000628:Aminophylline / Q000737:chemistry; D001993:Bronchodilator Agents / Q000737:chemistry; D004339:Drug Compounding; D004400:Dyphylline / Q000737:chemistry; D008863:Microspheres; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties; D013806:Theophylline / Q000737:chemistry; D014867:Water / Q000032:analysis; D014970:Xanthines / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D001993:Bronchodilator Agents; D014970:Xanthines; D014867:Water; D004400:Dyphylline; D000628:Aminophylline; D013806:Theophylline