Comparative in vitro–in vivo study of two quinine rectal gel formulations

Abstract

The main objective of this work was to develop and evaluate rectal quinine paediatric formulations to treat acute uncomplicated malaria attack in some African countries. Developed dosage forms must be able to assure a prolonged release in the rectum but not too much so as to avoid product expulsion by the child anus. Two quinine rectal gels, namely mucoadhesive (MA) gel and thermosensitive (TS) gel, containing 20 mg quinine base/g were developed and evaluated in vitro and in vivo in the rabbit. The MA and the TS gels contained hydroxypropyl methylcellulose 4000 (HPMC) and poloxamer 407, respectively. The calculated in vitro release exponent ( n) values suggested that drug was released from both gels by non-Fickian diffusion. Both gels exhibit practically similar efficient of dissolution (ED%) which was not reflected in the plasma and, therefore, quinine bioavailability from MA gel was found to be higher than that obtained from TS gel and their AUC 0–∞ were statistically different ( P = 0.0006). The t 1/2 values of quinine were significantly higher for Hydrogels than for IV and rectal solutions. MRT values displayed by TS gel and MA gel were not statistically different but were about 3.8- and 1.3-fold, respectively, larger than those obtained for IV solution and rectal solution, respectively. These results confirm the sustained-release behaviour of both hydrogels in the rabbit. Tolerability study of hydrogels didn’t show any damage on the rectal mucosa of the rabbit.