Crystalline and amorphous carvedilol-loaded nanoemulsions: formulation optimisation using response surface methodology

This study aimed to evaluate the crystalline and amorphous carvedilol along with their lipidic mixtures using various instrumental techniques and to use response surface methodology in conjunction with factorial design to establish the functional relationships between operating variables (capmul GMS 50K and cremophor RH 40). The response variables selected are spectroscopic absorbance (Y-1), mean particle size in distilled water (Y-2) and in phosphate buffer pH 6.8 (Y-3), polydispersibility index (PDI) (Y-4) and zeta potential (Y-5). The optimal formulations of crystalline and amorphous carvedilol-loaded nanoemulsions were composed of fixed levels, -0.41 and -0.42, of capmul GMS 50K and cremophor RH 40, respectively. The predicted and observed values of Y-1-Y-5 for blank nanoemulsions showed the percentage bias error of -12.12%, -10.25%, -18.47%, +14.81 and -2.89, respectively. The bias percent ranged between -2.70% and -29.41% for the responses Y-1-Y-4 for both crystalline and amorphous carvedilol-loaded nanoemulsions, indicating high degree of prognosis. However, the bias percent values for the response variable Y-5 were 294.2% and 262.6%, for the crystalline and amorphous carvedilol-loaded nanoemulsions, respectively, possibly due to cationisation of emulsion droplets. The transmission electron microscopy of selected optimal nanoemulsions showed the spherical shape of globules with no signs of coalescence and precipitation of drug. This study demonstrates the use of factorial design for the preparation of nanoemulsions of crystalline and amorphous carvedilol. The desirable goals can be obtained by systematic formulation approach in the shortest possible time.