title: Formulation and in vivo evaluation of chlorpropham (CIPC) oral formulations.
abstract: The objective of these studies was to examine the in vivo performance of oral formulations of chlorpropham (CIPC). In order to develop a new oral formulation several different solubilization techniques were evaluated, namely: cosolvents, surfactants, and complexing agents. The solubilization data indicated that a conventional solution formulation was not plausible. Two self-emulsifying drug delivery systems (SEDDS) were developed and evaluated for stability. Both SEDDS formulations were found to be chemically stable. In vivo analysis of a SEDDS formulation, a suspension formulation and an intravenous bolus dose was conducted in F344 rats. Pharmacokinetic analysis of the formulation data indicated that the SEDDS formulation provided only marginally better oral bioavailability compared to a suspension formulation. While SEDDS formulations often result in greater bioavailability this was not observed for CIPC. In vivo analysis indicate that CIPC results in a situation where the dissolution rate of CIPC from the suspension is not rate limiting, rather the absorption rate in the GI tract is rate-limiting. This paradigm is the result of CIPCs low melting point and the relatively small particle size of the suspension which facilitate the dissolution in the GI tract.
authors.affiliation: Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, New Mexico 87108, USA. pkuehl@lrri.org
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kuehl
authors.forename: Tim
authors.initials: T
authors.lastname: Brenner
authors.forename: Parijat K
authors.initials: PK
authors.lastname: Jain
authors.forename: Kelly
authors.initials: K
authors.lastname: Karlage
authors.forename: Kia
authors.initials: K
authors.lastname: Sepassi
authors.forename: Gang
authors.initials: G
authors.lastname: Yang
authors.forename: Michael
authors.initials: M
authors.lastname: Mayersohn
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Yalkowsky
authors.forename: Paul B
authors.initials: PB
authors.lastname: Myrdal
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002748:Chlorpropham / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D010316:Particle Size; D051381:Rats; D011916:Rats, Inbred F344; D012995:Solubility
chemical_list: D002748:Chlorpropham