title: Modification of drug release from acetaminophen granules by melt granulation technique - consideration of release kinetics.
abstract: Acetaminophen granules have been formed by a melt granulation process with the objective of retarding drug release for prolonged action formulations. The waxes used were goat wax, carnuba wax and glyceryl monostearate. In the melt granulation procedure, acetaminophen powder was triturated with the melted waxes and passed through a sieve of mesh 10 (aperture size 710 microm). The content of wax in resulting granules ranged from 10 to 40%w/w. Acetaminophen granules were also formed by the convectional method of wet granulation with starch mucilage (20%w/w). The granules were subjected to in-vitro drug release tests. The release data were subjected to analysis by three different well-established mathematical models (release kinetics) namely, - zero order flux, first order, and the Higuchi square root of time relationship. The convectional granules exhibited an initial zero order flux (first 55%) followed by a first order release profile (the remaining 45%). The pattern of drug release from the melt granulations was consistent with the first order kinetic and the Higuchi square root of time relationship, indicating a diffusion-controlled release mechanism. The first order release rate constant of the convectional granules was 1.95 +/- 0.02 h(-1). After melt granulation (wax content, 20%w/w) the rate constants dropped drastically to 0.130+/-0.001 h(-1) (goat wax), 0.120+/-0.003 h(-1) (carnuba wax), and 0.130+/-0.002 h(-1) (glyceryl monosterate) indicating that all three waxes were equivalent in retarding drug release from the melt granulations.
authors.affiliation: Department of Pharmaceutics, University of Benin, Benin City, Nigeria. mike2003@yahoo.com
authors.forename: M U
authors.initials: MU
authors.lastname: Uhumwangho
authors.forename: R S
authors.initials: RS
authors.lastname: Okor
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D000273:Adipose Tissue / Q000737:chemistry; D000818:Animals; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D005989:Glycerides / Q000737:chemistry; D006041:Goats; D007700:Kinetics; D011208:Powders; D012995:Solubility; D014885:Waxes / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D005989:Glycerides; D011208:Powders; D014885:Waxes; C048159:glyceryl monostearate; D000082:Acetaminophen