Self-Emulsifying Pellets: Relations Between Kinetic Parameters of Drug Release and Emulsion Reconstitution—Influence of Formulation Variables

Abstract

The effects of surfactant type and content on the kinetics of emulsion reconstitution and release of drugs differing in lipophilicity from self-emulsifying microcrystalline cellulose pellets were studied. Furosemide and propranolol were the drugs, medium-chain triglyceride was the oil, and Cremophors ELP, RH40, and RH60 were the surfactants. Pellets were prepared by extrusion/spheronization with emulsions (75% water and 25%, w/w, oil/surfactant/drug). Stability of the emulsions was evaluated from changes in the back-scattered light, and re-emulsification and drug release from light transmittance and UV spectroscopy, respectively. Emulsion stability increased because of the incorporation of the drugs. Re-emulsification depended only on the surfactant content and was expressed by a simple power equation (Ra2 > 0.945, Q(2) > 0.752). Drug release was expressed by two biexponential equations (Ra2 > 0.989, Q(2) > 0.699 and Ra2 > 0.947, Q(2) > 0.693) implying initial burst and terminal slow release phase and by the linear form (Lineweaver-Burke) of Michaelis-Menten equation (Ra2 > 0.726, Q(2) > 0.397). Relationships exist between the rate constants of the equations describing emulsion reconstitution and drug release, for propranolol compositions (R(2) = 0.915), and for compositions of both drugs with less hydrophilic ELP and RH40 (R(2) = 0.511), and also, among dissolution efficiency, drug solubility in oil/surfactant, and emulsion reconstitution ability, indicating the importance of drug solubilization in oil/surfactant and re-emulsification ability on drug release.