In the present era, there is an immense need for the pharmaceutical industries to step forward, contrive novel effectual drug formulations and techniques to ameliorate the existing products. On the other hand, lack of scale up techniques and commercial procedures were the reason for the failure of the novel drug delivery system (DDS) to enter the market. Therefore, the pharmaceutical industries are in search of effective, reproducible and simple methods for producing DDS. A continuous search is on to find out better techniques for generating DDS, and to make a positive impact on the conventional techniques. Recently, ultrasound cavitation has gained importance due to its widespread use in a variety of processes i.e. physical, chemical and biological [1] . Research in ultrasound-activated novel delivery has emerged widely in the last two decades with the origination of gas bubbles [2] . High energy ultrasonic vibrations are tried for designing and formulating the various novel DDS [3] . Recently, in novel aspects, advantages of ultrasound technology in terms of intensification and low energy requests for microencapsulation are emphasized [4] . Generation of microspheres using cavitation approach is highly energy efficient and also flexible to control particle size over other conventional mechanical and high-pressure techniques [5] . The impact of process parameters such as the flow rate and liquid properties on the size distribution and effect of other equipment parameters like the operating frequency, power dissipation have also been evaluated over conventional methods [6] . The objective of this study is to demonstrate an effective technique with potential for commercialization for microsphere production. Ultrasound-assisted ionic gelation of sodium alginate was used to encapsulate simvastatin. Chitosan was used as a mucoadhesive polymer for gastroretention of microsphere. Sodium alginate solution was sonicated using probe sonicator at a frequency of 20±3 KHz and ultrasonic power of 130 W with an input voltage range of 170-270 AC, 50 Hz, at a temperature of 50°. The influence of ultrasound waves on drug entrapment efficiency, yield and particle size dispersion was studied in comparison to mechanical stirring method. Mucoadhesiveness, release pattern and kinetics of drug release were also characterized. Ultrasound treatment caused small fissures and depressions on the surface of alginate as evidenced in SEM. Ultrasound of 20±3 KHz for 12 min duration was the optimum frequency and time in the experimental set up to obtain microspheres with uniform and smaller microparticles. The encapsulation efficiency of simvastatin was directly proportional to the sonication effect, concentration of alginate and extent of its cross linkage with calcium ions. DSC studies revealed that ultrasound treatment did not alter the structural integrity of the drug component. Formulation was found to be dissolution efficient and drug release pattern was concentration-dependent, which followed non-Fickian diffusion mechanism with an 'n' v...