title: Investigation of the utility of an in vitro release test for optimizing semisolid dosage forms.
abstract: Current literature indicates that an in vitro release test (IVRT) can serve as a research tool during the course of developing topical formulations. The purpose of this study was therefore to investigate the ability of an IVRT to select the topical semisolid formulations with the most rapid release rate of the model drug ketoprofen from two closely related hydrogels in a simulated product development process. Two glycols with distinct differences in their physical-chemical properties, Transcutol P (ethoxydiglycol) and propylene glycol, were incorporated into Carbopol 980 and Poloxamer 407 formulations. The release rate of ketoprofen was determined utilizing different receptor media and conditions, i.e., phosphate buffer pH 7.4, isopropyl myristate (IPM), and a combination of an IPM soaked membrane and phosphate buffer (pH 7.4) as receptor fluid. The results indicated that the conditions chosen could affect greatly the conclusions concerning the formulations. The only observable trend was that Transcutol P-containing formulations tended to permit a faster ketoprofen release than propylene glycol-containing formulations when utilizing IPM as a receptor component. This was attributed to the mutual miscibility of Transcutol P in IPM. It can be concluded that, for the purpose of formulation screening in the early phases of product development, an IVRT will only be useful for predicting the amount of drug available for absorption if the receptor medium has properties that closely mimic human skin. These results illustrate the importance of selecting suitable receptor components and indicate that it may be necessary to consider alternatives to the commonly used synthetic membranes.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721, USA.
authors.forename: S
authors.initials: S
authors.lastname: Proniuk
authors.forename: S E
authors.initials: SE
authors.lastname: Dixon
authors.forename: J
authors.initials: J
authors.lastname: Blanchard
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics*; D004058:Diffusion; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005026:Ethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D005079:Excipients / Q000737:chemistry / Q000493:pharmacokinetics; D020100:Hydrogels / Q000737:chemistry / Q000493:pharmacokinetics; D007660:Ketoprofen / Q000737:chemistry / Q000493:pharmacokinetics*; D020442:Poloxamer / Q000737:chemistry / Q000493:pharmacokinetics; D019946:Propylene Glycol / Q000737:chemistry / Q000493:pharmacokinetics; D011480:Protease Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005026:Ethylene Glycols; D005079:Excipients; D020100:Hydrogels; D011480:Protease Inhibitors; D020442:Poloxamer; D019946:Propylene Glycol; D007660:Ketoprofen; C010111:carbitol