Formulation of Rectal Supopositories of Omeprazole

오메푸라졸 함유 직장좌제의 제제설계

In order for formulation of rectal containing OMZ, the OMZ suppositories were prepared using water-soluble base, PEG 4000 base and oil-soluble base, Witepsol H 15. Chemical stability of OMZ in suppositories was increased when Witepsol H 15 was used as a suppository base and arginine was added as a stabilizer. The decomposition of OMZ in suppository bases followed the first-order kinetics and their rate constants were 0.11 day $^{1}(t_{1/2}$=/6.25 days) for Witepsol H 15 suppository and 0.48 day $^{1}(t_{1/2}$=/1.43 days) for PEG 4000 suppository, respectively. On the other hand, the decomposition rate constants of Witepsol suppository and PEG suppository stabilized with arginine were 3.89$\times$10$^{-3}$(t$_{1/2}$=171.1 days) and 8.76$\times$10$^{-3}$ day $^{1}(t_{1/2}=79.9 days), respectively. Shelf-lives of the Witepsol and PEG suppositories stabilized with arginine were t$_{90%}$=291.8 days and t$_{90%}$=282.1 days at $35^{\circ}C$ and 75% RH, respectively. The dissolution test of OMZ suppositories was performed by rotating dialysis cell(RDC) method and the release rate constant was calculated by the simplified Higuchi's equation, Q'=K' t$^{1/2}$. Dissolution of OMZ from suppositories was augmented as arginine was added, particle size of OMZ was reduced and a suitable surfactant such as SLS was added. RDC method was more appropriate and available than Paddle method to evaluate the dissolution rate of lipophilic-base suppositoies. Arginine was found to be a very useful exipient for the enhancement of stability and dissolution of OMZ in suppositories.