Odidi, Amina I.; (1990) Taste-masked and controlled-release formulations of quinine. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Due to the widespread emergence of chloroquine-resistant P. falciparum quinine became important again in malaria chemotherapy. Because of possible toxicity with parenteral routes it is often administered orally, frequently causing gastric irritation. Although malaria affects children mainly, there is no known paediatric formulation of quinine, the bitter taste of which is not masked by sweetening. From clinical experience, sustained-release of quinine would decrease the occurrence of treatment failure. In this work, taste-masked and sustained-release quinine was formulated by a modified multiple emulsion technique of microencapsulation. It involves ionic interaction between drug and polymer in the inner aqueous phase of multiple emulsions. Two formulations were prepared using the anionic polyelectrolytes iota-carrageenan, a sulphated polysaccharide and Eudragit L, an acrylic resin. In principle, transfer of quinine from an oil to an aqueous phase, and the binding of quinine to hydrocolloid electrolytes were demonstrated. In vitro release of quinine was faster at lower pH values implying controlled release in the mouth, and the release kinetics were complex. Bioavailability studies and taste evaluation were carried out using healthy human volunteers. Plasma levels were more sustained in the microcapsules than the control. The release mechanism, in vitro-in vivo correlation, the different release rates from the two microcapsules and the relevance of in vivo results to malaria chemotherapy were discussed. It appears that dose forms could be designed from these, to provide sustained action of quinine. The bitter taste was shown to be substantially reduced. Thus these microcapsules could be used for taste coverage, administered as extemporaneous suspensions. The modified process was shown to load more drug and provide better control of release. Two other cationic drugs, acetaminophen and cimetidine were encapsulated and characterised. The drug content depended on the number of acidic groups on a polymer and the basicity of the drug. Drug loss was further minimised when the drug was in the oil phase initially. In vitro release rates depended on the strength of drug-pol5mier interaction. Hence this procedure could be applied for the controlled release of suitable drugs. Some progress was also made in the development of a buccal quinine dosage form using a cross-linked alginate network. Buccal delivery would eliminate gastric irritation.

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