Effect of Pharmaceutical Excipients on Cloud Point of Amphiphilic Drug Venlafaxine Hydrochloride Solutions

Abstract

One of the characteristics of amphiphilic drug which may be a disadvantage is the phase separation or clouding phenomenon on heating which depends upon the nature, structure and concentration of the amphiphile, pressure, presence of additives, etc. The effect of various types of pharmaceutical excipients such as hydrotropes and β-cyclodextrin on the cloud point (CP) behaviour of amphiphilic drug venlafaxine hydrochloride (VFN) in sodium phosphate buffer sodium phosphate buffer (pH 6.7) solutions have been investigated in the present study. The anionic hydrotropes (sodium benzoate and sodium salicylate) increase the CP of VFN, when added in low concentrations, whereas at high concentration, decrease it. Cationic and non-ionic hydrotropes increase the CP of VFN solution at all the concentration. β-cyclodextrin behave like simple sugar is found to decrease the CP of the drug solutions at all concentrations. The thermodynamic parameters are also evaluated: where ΔG° is found to be negative and ΔH° and TΔS° values are negative as well as positive depending upon type and nature of hydrotropes. Based upon the result, storing formulations at temperatures significantly higher than the cloud point may result in phase separation and instability.