title: 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.
authors.affiliation: Department of Pharmaceutical Technology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Nikolakakis
authors.forename: Stavros
authors.initials: S
authors.lastname: Malamataris
mesh_terms: D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D004343:Drug Implants / Q000737:chemistry*; D065546:Drug Liberation; D004655:Emulsions / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D005665:Furosemide / Q000737:chemistry; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D007700:Kinetics; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D004343:Drug Implants; D004655:Emulsions; D005079:Excipients; D009821:Oils; D004364:Pharmaceutical Preparations; D013501:Surface-Active Agents; D014867:Water; C000515:cremophor EL; D005665:Furosemide; D002482:Cellulose; D011433:Propranolol; C109691:microcrystalline cellulose; D005990:Glycerol
keywords: dissolution rate; extrusion; kinetics; light-scattering; log P; physical stability; self-emulsifying; solubility; spheronization; surfactants