t1/2. Mechanism of drug release according to Korsmeyer–Peppas model was evaluated by fitted first 60% of Z-VAD-FMK in vivo drug release in following equation and release exponent “n” was calculated from plot Log cumulative % drug release vs. Log time. 9, 10 and 11 equation(7) Mt/M∞=kptnMt/M∞=kptnwhere, Mt/M∞ is the
fraction of drug release at time t, n is the release exponent and kp is the rate constant. The statistical significance of the difference in viscosities, particle size, % EE between the different nanoparticle formulations were tested by one-way analysis of variance (ANOVA) Graphpad Instat® Version 3.06 software. Differences were considered to be statistically significant at a level of p ≤ 0.05. Metformin HCl loaded ethylcellulose nanoparticles were formulated by non-aqueous oil in oil solvent emulsion evaporation technique. Methanol was used as common solvent for drug and polymer because it was also immiscible GSK2656157 order with LLP. Metformin HCl and ethylcellulose are insoluble in LLP. This way organic phase and oil phase was totally immiscible with each other. The reason behind to set such a scheme was that, metformin HCl is highly water soluble drug therefore use of water as external
phase may cause drug loss during emulsion formation step and also confer burst release effect as utmost drug was at surface and not in core of the particles.12 So, we do efforts to reduce the initial burst release have followed in the same track as those to increase entrapment efficiency. When we added organic phase in oil phase with high speed homogenization the oil soluble surfactant SPAN 80 decreased the interfacial tension between both the phases and reduced the size of polymeric globules. Homogenization at 25,000 rpm increased the temperature of
external oil phase above room temperature, this facilitate evaporation rate of methanol from emulsion. So, high speed homogenization, surfactant concentration, lipophobic properties of drug and polymers and evaporation rate were combine influenced on size reduction and solidification of nanoparticles. We used ethylcellulose of three different viscosity grades to encapsulate metformin HCl. As given in method, by each viscosity grade polymer three increasing drug-polymer ratios were studied. From obtained results it was concluded that as drug-polymer ratio increased, before the viscosity of internal organic phase also increased (p < 0.05) which affects on particle size only (p < 0.05), not significantly on encapsulation efficiency of recovered nanoparticles ( Table 1). Lower viscous organic phase produced smaller particle size because it ruptured in very small globules without confrontation to mass transfer. It had more spreading competency in external phase leading to formation of smaller nanoparticles. Contrary to lower viscosity, high viscous organic phase was difficult to disperse in external phase due to higher mass transfer resistance leads larger droplets and formed larger nanoparticles.