Investigation of Effect of Non-Ionic Stabilizers on the Physical Stability of Drug Nanosuspension Prepared By Bottom Up Approach

Abstract

In this research work, the effects of nonionic stabilizers on the physical stability of drug nanosuspensions were investigated. For this purpose five nonionic polymers (hydroxypropylmethyl cellulose (HPMC), Hydroxypropyl cellulose (HPC), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP) and pluronic F68) and esomeprazole were selected as stabilizers and drug candidate, respectively. All the nanosuspensions were prepared using bottom up approach. The potential of Ostwald ripening for the nanosuspensions was investigated by subjecting them to various stress conditions such as storage at various temperature conditions (15°C, 25°C, 35°C, 45°C), mechanically shaking for 72 hours and fluctuation in storage temperature. All the polyvinylpyrrolidone and hydroxypropyl cellulose based formulations that were stored under different stress conditions exhibited the increase in particle size. In other cases the highest increase in mean particle size was observed at 45oC, followed by 35°C. Samples stored at 15°C and 25°C did not exhibit the significant changes in particle size. The HPMC 1 formulation stored at 45°C, exhibited a steep increase in particle size, probably due to desolvation of the HPMC molecules at this temperature and subsequent loss of stabilization of the nanoparticles. However, in case of HPMC 2 and HPMC 3 formulations (stored at 45°C), the gradual increase in particles size was obtained. This trend of increase in particle size was attributed to presentation of excess amount of HPMC. Powder X-ray diffraction analysis confirmed that all the prepared nanosuspensions were in crystalline state. Hence, physical treatments and other factors did not change the crystalline state of nanosuspensions. To Confirm the crystalline state of those samples which were undergo for 3 cycles of temperature fluctuation, the DSC (Differential scanning calorimetry) analysis was performed, and compare with raw drug. Esomeprazole exhibited the melting endotherm at an onset temperature of 178.1°C and a peak temperature at 185.31°C. The thermogram revealed that crystalline state of raw drug was not changes but the melting peak drifted slightly due to presence of stabilizers.