Formulations and pharmacokinetics of prolonged release ketoprofen rectal suppositories

Abstract

Formulations and pharmacokinetics of prolonged release ketoprofen rectal suppositories were studied. Formulations were conducted using three hydrophilic suppository bases and two prolonged release carriers (Eudragit S-100 and HP55). The amount of each carrier used was dependent on the drug to carrier ratios. Various ratios of the drug to Eudragit S-100 or HP55 were individually assigned to each base. A commercially available hydrophobic base (Suppocire ®AM) was also used for comparison. All formulations with 100 mg ketoprofen were prepared by fusion method. In vitro evaluations showed that they met the requirements for uniformity of weight and uniformity of content according to the British Pharmacopoeia 1993. All release profiles were slow and prolonged compared to those without the two carriers. The formulation with Eudragit S-100 at the ratio of 1:1 in Base 1 and that with HP55 at the ratio of 1:4 in Base 3 were subsequently selected for in vivo studies. Pharmacokinetics of the two selected formulations and the one with Suppocire® AM were performed using nine New Zealand White rabbits. Each rabbit received a single rectal dose of 100 mg prolonged release ketoprofen rectal suppository in a crossover manner. Blood samples were collected at predetermined time intervals post dose and determined for ketoprofen, concentrations by HPLC. Results demonstrated that the pharmacokinetic patterns of ketoprofen from all three formulations were similar and appeared to be multicompartment model. Analysis of variance for three-way crossover design revealed that there were no significant differences (p>0.05) among all the corresponding relevant pharmacokinetic parameters obtained. Both formulated products were bioequivalent with the reference formulation with respect to the rate and the extent of drug absorption. The two carriers produced the same efficacies but Eudragit S-100 was slightly superior based on the amount being used was lesser and the ease of preparation.