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Isoniazid (INH) is a first-line chemotherapeutic drug employed in the management of tuberculosis. However, its extensive first-pass metabolism, short-life life, and low oral bioavailability confined its medical application. Therefore, the calcium ion-alginate-piperine microspheres (INH-CaSP Ms) was prepared to enhance encapsulation efficiency, controlled delivery, and oral bioavailability of INH. The INH-CaSP Ms was developed using a modified emulsification method and optimized via Box-Behnken design (BBD). Optimized INH-CaSP Ms were char