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Calcium Ion-Sodium Alginate-Piperine-Based Microspheres: Evidence of Enhanced Encapsulation Efficiency, Bio-Adhesion, Controlled Delivery, and Oral Bioavailability of Isoniazid

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Abstract

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 characterized for encapsulation efficiency, differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), bio-adhesion, in vitro dissolution, ex vivo permeation, and oral bioavailability studies. Characterization studies confirmed the formation of microspheres. The INH-CaSP Ms showed spherical microspheres with enhanced encapsulation efficiency (~ 93.03 ± 1.54% w/w). The optimized INH-CaSP Ms exhibited higher bio-adhesion around (~ 81.41 ± 1.31%). The INH-CaSP Ms enhanced the dissolution rate of INH (~ 57%) compared to pure INH (~ 57%) and INH-SA Ms (~ 81%) in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.4). The same formulations improved the permeation rate of INH (~ 90%) compared to pure INH (~ 55%) and INH-SA Ms (~ 80%). The oral bioavailability results indicated that INH-CaSP Ms appreciably improved the oral bioavailability of INH via increasing the Cmax, Tmax, t1/2, and AUC parameters compared to pure INH. The study demonstrates that the development of INH-CaSP Ms via cross-linked coordinate bond interaction between divalent cation calcium ion-alginate complex and anion piperine bio-enhancer is an effective approach for enhancing the encapsulation efficiency, bio-adhesion, controlled release, and oral bioavailability of INH.

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Acknowledgements

The corresponding author thanks Dr. Ravindra RP, Ph.D. supervisor of School of Pharmacy and Technology Management, SVKM’s NMIMS, Shirpur, for providing all the essential facilities to complete this project.

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The conducted research did not receive any funding from the university and government agencies.

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Authors and Affiliations

  1. Rajarshi Shahu College of Pharmacy, Maharashtra, Buldhana, India

    Darshan R. Telange & Shirish P. Jain

  2. School of Pharmacy and Technology Management, SVKM’s NMIMS (Deemed to be University), Shirpur, Maharashtra, India

    Ravindra R. Pandharinath

  3. Datta Meghe College of Pharmacy, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (Meghe), Wardha, Maharashtra, India

    Darshan R. Telange & Anil M. Pethe

  4. GES’s Sir Dr. M. S. Gosavi College of Pharmaceutical Education and Research, Nashik, Maharashtra, India

    Prashant L. Pingale

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Contributions

Darshan R Telange: analysis, interpretation of data for the work, drafting of the work, editing. Ravindra R Pandharinath: conceptualization, supervision, visualization, interpretation of the data for the work. Anil M Pethe: design of the work, writing of the original draft, investigation. Shirish P Jain: Analysis, validation, data curation. Prashant L Pingale: design of the work, analysis, interpretation of data for the work, final approval of the version to be published.

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Correspondence to Prashant L. Pingale.

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Telange, D.R., Pandharinath, R.R., Pethe, A.M. et al. Calcium Ion-Sodium Alginate-Piperine-Based Microspheres: Evidence of Enhanced Encapsulation Efficiency, Bio-Adhesion, Controlled Delivery, and Oral Bioavailability of Isoniazid. AAPS PharmSciTech 23, 99 (2022). https://doi.org/10.1208/s12249-022-02236-6

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