Novel Drug Delivery Systems Containing Artesunate And Amodiaquine

ABSTRACT 

Globally, an estimated 3.4 billion people are at risk of malaria, including Nigerians. The current World Health Organization (WHO) Guideline for the treatment of malaria recommends the use of artemisinin combination therapy (ACT) for the treatment of uncomplicated malaria. Presently, the available formulations of ACTs are administered through the oral route. Rectal administration, which formed the basis of this work, is an alternative route of administration which overcomes the limitations of oral and parenteral administration of drugs. Differential Scanning Calorimetry (DSC) was employed to study the compatibility between artesunate, amodiaquine and the suppository bases and to determine the optimum ratio of the excipients. Three batches of structured suppositories of artesunate and amodiaquine (ACT) were formulated by the melt moulding (fusion) technique, evaluated for various parameters including physical characterization, weight variation, drug content, morphology and in vitro drug release. The drug release data were analyzed by zero order and Higuchi models. The suppositories were further evaluated in mice against virulent rodent malaria parasite Plasmodium berghei using Peter’s 4 days suppressive protocol. Data were expressed as mean ± SD. The parasitemia of the different groups were statistically assessed by ANOVA. The compatibility results proved that artesunate and amodiaquine are compatible. The optimum excipient ratio as determined by DSC was 4:4:3 for Phospholipon®90G-Softisan®154 matrix, Castor oil, and PEG 4000 respectively. The colours of the prepared suppositories ranged from light yellow to deep yellow; no fissures, fat blooming, exudation or migration of active ingredients was observed. The weight variation of all the suppositories met the BP Standards, with uniform drug content. The release profile for artesunate ranged from 99.21 % to 81.31 % and from 99.89 % to 28.81 % for amodiaquine. The developed suppositories reduced parasitemia to undetectable levels 28 days after drug administration. The survival rate of animals treated with E and PS suppositories was 100 %, while the survival of animals treated with P was 80 %, 55 days after drug administration. The results of the hemoglobin and hematocrit tests 55 days after drug administration revealed that the blood levels were normal for animals in the treatment groups. Stability studies revealed that the suppositories stored at 4 o C were more stable than the suppositories stored at 27 o C