title: Kinetics of drug release from ointments: Role of transient-boundary layer.
abstract: In the current work, an in vitro release testing method suitable for ointment formulations was developed using acyclovir as a model drug. Release studies were carried out using enhancer cells on acyclovir ointments prepared with oleaginous, absorption, and water-soluble bases. Kinetics and mechanism of drug release was found to be highly dependent on the type of ointment bases. In oleaginous bases, drug release followed a unique logarithmic-time dependent profile; in both absorption and water-soluble bases, drug release exhibited linearity with respect to square root of time (Higuchi model) albeit differences in the overall release profile. To help understand the underlying cause of logarithmic-time dependency of drug release, a novel transient-boundary hypothesis was proposed, verified, and compared to Higuchi theory. Furthermore, impact of drug solubility (under various pH conditions) and temperature on drug release were assessed. Additionally, conditions under which deviations from logarithmic-time drug release kinetics occur were determined using in situ UV fiber-optics. Overall, the results suggest that for oleaginous ointments containing dispersed drug particles, kinetics and mechanism of drug release is controlled by expansion of transient boundary layer, and drug release increases linearly with respect to logarithmic time.
authors.affiliation: Division of Product Quality Research, OTR/OPQ, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Electronic address: Xiaoming.Xu@fda.hhs.gov.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Product Quality Research, OTR/OPQ, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Electronic address: Manar.Al-Ghabeish@fda.hhs.gov.
authors.forename: Manar
authors.initials: M
authors.lastname: Al-Ghabeish
authors.affiliation: Division of Product Quality Research, OTR/OPQ, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Electronic address: Krishnaiah.Yellela@fda.hhs.gov.
authors.forename: Yellela S R
authors.initials: YS
authors.lastname: Krishnaiah
authors.affiliation: Division of Product Quality Research, OTR/OPQ, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Electronic address: Ziyaur.Rahman@fda.hhs.gov.
authors.forename: Ziyaur
authors.initials: Z
authors.lastname: Rahman
authors.affiliation: Division of Product Quality Research, OTR/OPQ, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Electronic address: Mansoor.Khan@fda.hhs.gov.
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D000212:Acyclovir / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D065546:Drug Liberation; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009823:Ointment Bases / Q000737:chemistry; D009824:Ointments / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010825:Physics; D012995:Solubility; D013696:Temperature
chemical_list: D005079:Excipients; D009823:Ointment Bases; D009824:Ointments; D004364:Pharmaceutical Preparations; D000212:Acyclovir
keywords: Acyclovir; Higuchi model; In vitro drug release; Kinetics; Logarithmic time release; Ointment; Transient-boundary