Preparation and Optimization of Esomeprazole Nanosuspension using Evaporative Precipitation– Ultrasonication

Purpose: To prepare and optimize esomeprazole nanosuspension to enhance drug dissolution rate.
Methods: Esomeprazole nanosuspensions were prepared by evaporative precipitation-ultrasonication method using F68 (Poloxamer 188) and F127 (Poloxamer 407) as stabilizers. Formulation and process variables (concentration of stabilizers and drug, power input and duration of ultrasonication) affecting the characteristics of nanosuspensions were optimized. The nanosuspensions were characterized for particle size, shape, zeta potential, stability and in vitro drug release study.
Results: For optimization of esomeprazole nanosuspension, the effect of some important parameters, including concentration of F68, concentration of esomeprazole, precipitation temperature, duration of ultrasonication and power input, on particle size were investigated, and the optimal values were 0.4% w/v, 3.5 mg/ml, 4°C, 20 min and 60% W, respectively. Particle size was in the range of 125 - 184 nm with good zeta potential (15.9 - 25.5 mV). In vitro dissolution rate of esomeprazole was enhanced 4-fold (100% in 60 min) compared with crude esomeprazole (24% in 60 min), and this was due to decrease in particle size. The stability results indicate that nanoformulations stored at 4°C for two months showed maximum stability.
Conclusion: The results indicate the suitability of evaporative-precipitation-ultrasonication method for preparation of nanosuspensions of poorly soluble drugs with improved in vitro dissolution rate, thus potentially capable of enhancing fast onset of therapeutic activity, and bioavailability.

Keywords
Agglomeration; Esomeprazole; Ultrasonification; Nanosuspension; Drug release; Solubility; Stability