The Effects of Surfactant and Storage Conditions on the In-Vitro Release of Quinine Suppository Made from Witepsol Base

Abstract

Background: The need to develop quinine suppository formulation as an alternative to the intravenous parenteral dosage form in severe cases of malaria necessitates this study. The aim is to demonstrate the effect of surfactant, polysorbate (Tween® 20), and storage conditions on the in-vitro release rate of quinine suppositories made from Witepsol H15 base.
Methods: Different batches of quinine bisulphate suppositories were made from Witepsol HI5 base by fusion method incorporating Tween® 20, as a surfactant at 0, 0.5, 1.0, 2.0 and 4.0 % w/w concentrations. Some of these suppositories were stored at room temperature (30 ± 2 ˚C) while the rest were stored in the refrigerator (10 + 2˚C) for a period of 21 days and were then analyzed. The physicochemical properties of the suppositories were determined by several tests which include content uniformity, melting range test, hardness and in- vitro drug release rate.
Results: The melting ranged from 20 – 30 min for suppositories without surfactant while those with the surfactant were from 3 – 12 min. Suppositories with surfactant had the same trend in hardness. For preparation containing 4% w/w of surfactant, (3800 - 4000 g pressure at room temperature and 3800 – 2600 g pressure in a refrigerator), respectively for days 1 and 12. The active constituent for 0, 0.5, 1.0, 2.0 and 4.0% w/w concentrations of incorporated Tween 20℗ were 98.00, 82.30, 77.60, 81.90 and 76.73 % respectively while the in-vitro release on day 1 after 60 min were 78.32 ± 0.34, 75.69 ± 0.66, 84.34 ± 0.35, 90.50 ± 0.10 and 98.10 ± 0.30 %.
Conclusion: This study on day 1 reveals an enhanced effect of the surfactant on the in-vitro release of quinine bisulphate from the suppositories with the highest effect being at the concentration of 4.0 % w/w of Tween 20. Storage of the suppositories at room temperature and refrigeration had a surprising effect of increasing hardness and softening the suppositories, respectively with time.

Keywords: Antimalarial; Quinine; Suppositories; Surfactant; Witepsol