title: Feasibility studies of utilizing disk intrinsic dissolution rate to classify drugs.
abstract: The purpose of this report was to investigate the feasibility of using disk intrinsic dissolution rate (DIDR) to determine solubility class membership. We employed a VanKel dissolution apparatus fitted with a Wood's intrinsic dissolution die. To test the robustness of the method, variations of DIDR with compression force, dissolution volume, distance of the drug disk from the bottom of the dissolution vessel, and drug disk rotation speed were studied using furosemide and metoprolol in pH 4.5 acetate buffer as a model system. The DIDRs of six low solubility and nine high solubility model drugs were then determined at pH 1.2, 4.5, and 6.8 and compared to their BCS solubility class membership. It was found that the compression force, dissolution medium volume, and die position had no significant effect on DIDR for the system studied. The proposed compression force, dissolution volume, die position, and rotation speed are 2000 psi, 900 ml, 0.5 in., and 100 rpm, respectively. The test results obtained from 15 model BCS drugs show a good relationship between the DIDR and BCS solubility classification with 0.1 mg/min/cm(2) as a class boundary unless the dose is either extremely low or high where discrepancies may exist between the solubility and DIDR methods. Therefore, more scientific research and debates are needed before considered for regulatory purpose.
authors.affiliation: Food and Drug Administration, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, 5600 Fishers Lane, Rockville, MD 20857, USA. yul@cder.fda.gov
authors.forename: Lawrence X
authors.initials: LX
authors.lastname: Yu
authors.forename: Alan S
authors.initials: AS
authors.lastname: Carlin
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Amidon
authors.forename: Ajaz S
authors.initials: AS
authors.lastname: Hussain
mesh_terms: D019245:Compressive Strength; D005240:Feasibility Studies; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000145:classification*; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations; D013607:Tablets