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Formulation, Evaluation, and Clinical Assessment of Novel Solid Lipid Microparticles of Tetracycline Hydrochloride for the Treatment of Periodontitis

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Abstract

The novel solvent-free process to formulate long-acting microparticles of tetracycline hydrochloride (TH) using hot melt extrusion granulation process coupled with size reduction using comil for the treatment of periodontitis was investigated using hydrogenated castor oil (HCO) as hydrophobic matrix former. The microparticles were characterized for micromeritics, drug diffusion, SEM studies, and stability analysis by DSC, FTIR, and proton NMR. Xanthan gum gel was used as delivery vehicles to administer microparticles inside periodontal pockets. The microparticles were sterilized using gamma radiation; delivery vehicle was sterilized using gamma radiation and autoclave process. Microparticles were evaluated for microbial load as per compendial guidelines. Optimized composition was evaluated for clinical parameters such as plaque index, gingival index, probing pocket depth, and clinical attachment level. Based on the statistical analysis of the data, the micromeritic properties and drug diffusion profiles vary based on the concentration of HCO in the formulation. SEM images reflect the surface properties prior and post drug diffusion studies, which indicates that release takes place predominantly by diffusion of TH through HCO matrix. DSC studies indicate no change in the respective spectra of initial and stability samples. FTIR studies indicate possibility of hydrogen bonding. Proton NMR data suggests characteristic peaks of TH being retained in the stability samples, indicating stable composition. Gamma radiation has led to significant reduction in viscosity of xanthan gum solution over autoclave. Clinical studies indicated statistical improvements in the formulation compared to baseline results, indicating the efficacy of the formulation in the treatment of periodontitis.

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Acknowledgments

We acknowledge DST (FIST), BASF India Limited and Nair Dental hospital, Mumbai, for their support in this research work. We also acknowledge ISOMED (BARC) and CIRCOT Mumbai for their valuable support.

Funding

The authors declare that the research work was carried out with support from Prin. K M Kundnani college of pharmacy and self-funding.

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Authors and Affiliations

  1. Department of Pharmaceutics, Prin. K.M. Kundnani College of Pharmacy, Plot No. 23, Jote Joy Building, Rambhau Salgaonkar Rd, Cuffe Parade, Mumbai, 400018, India

    Rajkiran Narkhede & Rajani Athawale

  2. Department of Periodontics, Nair Hospital Dental College, Dr. A. L. Nair road, Opposite Maratha Mandir, Mumbai Central, Mumbai, 400008, India

    Nikita Patil & MalaDixit Baburaj

Authors
  1. Rajkiran Narkhede
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Contributions

Rajkiran Narkhede: substantial contributions to the conception and design of the work; the acquisition, analysis, or interpretation of data for the work. Drafting the work or revising it critically for important intellectual content. Dr. Rajani Athawale: substantial contributions to the conception, design of the work; or the acquisition, analysis, or interpretation of data for the work. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Final approval of the version to be published. Dr. Nikita Patil: substantial contributions to the planning of clinical studies, drafting the clinical protocols, and execution of the clinical study. Final approval of the version to be published. Dr. Mala Dixit Baburaj: substantial contributions to the planning of clinical studies, drafting the clinical protocols, and execution of the clinical study. Final approval of the version to be published.

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Correspondence to Rajani Athawale.

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Narkhede, R., Athawale, R., Patil, N. et al. Formulation, Evaluation, and Clinical Assessment of Novel Solid Lipid Microparticles of Tetracycline Hydrochloride for the Treatment of Periodontitis. AAPS PharmSciTech 22, 162 (2021). https://doi.org/10.1208/s12249-021-02037-3

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