Formulation and evaluation of repaglinide microspheres

The present investigation involves formulation and evaluation of microspheres with Repaglinide as model drug for prolongation of drug release time. An attempt was made to prepare microspheres of Repaglinide by Quasi emulsion solvent diffusion technique, with a view to deliver the drug at sustained or controlled manner in gastrointestinal tract and consequently into systemic circulation. The microspheres were formulated by using various concentration of HPMCP, Ethyl cellulose and Eudragit RSPO as a retarding agent to control the release rate. The prepared microspheres were evaluated for Flow behavior, Compatibility study, Drug Entrapment Efficiency, In-vitro Dissolution, Scanning Electron Microscopy and Particle size analysis. Among the nine formulations prepared and evaluated F1 and F9 are found to show retarded release. In-vitro release studies indicated that, as the concentration of retarding agent (HPMCP, Eudragit and Ethyl cellulose) increases the formulation become more sustained. Key-Words: Repaglinide, Microsphere, Quasi-emulsion, In-vitro release Introduction Repaglinide induces rapid onset short lasting insulin release. It is administered before each measure meal to control postprandial hyperglycemia: the dose may be omitted if a meal is missed. Because of short lasting action it may have a lower risk of serious hypoglycemia. The quasi-emulsion solvent diffusion method of spherical crystallization technique has been accepted as a useful technique for particle size design for pharmaceuticals. It provides remarkable advantage over conventional microsphere preparation methods. In this process, drug and polymer are co precipitated to form functional drug devices according to the polymer properties. For example, acrylic resin (Eudragit RS,Eudragit RL) and Ethyl Cellulose (EC) could produce sustained release microspheres.However, further application of quasi-emulsion solvent diffusion method to produce solvent disposition system with poorly water soluble drug to improve the dissolution rate has seldom been reported until now. * Corresponding Author E-Mail: [email protected], [email protected] Mob.: +91-9753822226 In this study,the principles of above two methods were combined to design the sustained-release microspheres having solid dispersion structure of poorly watersoluble drug.Release of core material from a nonerodible microparticle can occur in several ways. Nonerodible spherical microparticles release the encapsulated material by steady-state diffusion through a coating of uniform thickness. The rate of release remains constant as long as the internal and external concentration of core material and concentration gradient through the membrane are constant. Material and methods Preparation of microsphere All the formulations were prepared according to the formulae given in Table 1. The microspheres were prepared using the quasi emulsion solvent diffusion method of spherical crystallization technique. In the first three formulation Repaglinide was dissolved with HPMC Phthalate, Ethyl Cellulose and Eudragit RSPO in mixed organic solution containing ethanol, acetone and dichloromethane then aerosil was suspended uniformly in drug polymer solution under vigorous agitation and Propylene Glycol was added as plasticizer; the resultant drug polymer aerosil suspension was poured in water phase containing (SLS) 0.08% that is poor solvent under moderate agitation 500-1000rpm at controlled temp 0-40 ̊c.The suspension, finely dispersed into quasi emulsion droplet, after10min agitation, 200ml of poor solvent was added to it and agitation was continued for 40min until translucent microspheres turned into opaque Research Article [Gupta et al., 3(2): Feb., 2012]