Bioavailability of ketprofen liquid filled in coated hard gelatin capsule for rectal use in rabbits

Abstract

Formulation and bioavailability of ketoprofen liquid filled in coated hard gelatin capsule were studied. Formulation of 100 mg ketoprofen was conducted using the combination of three cosolvents (PEG 1500, PG and either Tween 60®, Tween 80® or Dimethly isosorbide). The dissolution from all formulations were increased by using higher concentration of Tween 60® Tween 80® or Dimethyl isosorbide from 10% to 30%. The formulation with 20% Tween 80® and that with 20% Dimethyl isosorbide were subsequently selected for further in vitro and in vivo studies. In vitro evaluation showed that both formulations met the requirement for uniformity of content according to British Pharmacopoeia 1993. Dissolution and disintegration times of coated rectal capsule were longer than those without coating. For stability study, it was found that amount of drug in formulation was decreased after 3 months storage at 40 ℃ with 75% RH and deep yellow formulation was observed. Bioavailability of the two selected formulations and Oruvail® were performed using twelve white New Zealand rabbits. Each rabbit received a single dose of each ketoprofen formulation. Blood samples were collected at predetermined time intervals post dose and determined for ketoprofen concentrations by HPLC. Result demonstrated that ketoprofen was well absorbed from rectal coated capsule into systemic circulation. The relevant pharmacokinetic parameters of both ketoprofen rectal formulations were not statistically significant differences except the Cmax values. Relative bioavailability of each formulation with respect to Oruvail® was found to be 127 and 107%, respectively.