title: IV-IVC for topically applied preparations--a critical evaluation.
abstract: In vitro-in vivo correlation (IV-IVC) is the relationship between an in vitro parameter (drug release or other rheological properties/measurement such as viscosity and spreadability) and an in vivo parameter (pharmacodynamic (PD) or dermatopharmacokinetic (DPK) or other measurement). In a true sense of correlation, in vitro measurement should predict in vivo performance of the product. For topically applied preparations, one of the in vitro measurements is the drug release from the formulation and in vivo measurement is the drug concentration in the stratum corneum, DPK or the PD measurements. The in vitro release of the drug is the property of the dosage form and is a measure of product quality and 'sameness', especially after certain Scale-UP and Post Approval Changes after initial drug approval. To obtain an IV-IVC for a topically applied drug product is a difficult challenge. However, some success has been achieved in showing a relationship between the drug release and PD and/or DPK measurement. Interestingly, one of the in vitro rheological properties was found to relate to the observed PD and DPK response for Clobetasol dipropionate products. Different rheological properties of the two formulation products explained the difference in DPK results obtained by two laboratories for the same tretinoin gel products. In the scientific arena, it is difficult to obtain a classical IV-IVC even for orally administered products and is more so difficult for topically administered drug products.
authors.affiliation: Office of Pharmaceutical Science, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA. shahvi@cder.fda.gov
authors.forename: Vinod P
authors.initials: VP
authors.lastname: Shah
mesh_terms: D000287:Administration, Topical; D006801:Humans; D010599:Pharmacokinetics; D012867:Skin / Q000378:metabolism*; D012995:Solubility; D014783:Viscosity