Optimization and evaluation of sirolimus nanodispersion drug-layered prednisolone tablets for the management of  thrombocytopenia

Pradeep  Jena; Achal  Mishra; Madhuri  Baghel; Mayank  Garhewal; Shekhar  Verma

doi:10.69857/joapr.v14i4.2307

Authors

Pradeep Jena Faculty of Pharmaceutical Sciences, SSTC Bhilai, Affiliated to Chhattisgarh Swami Vivekanand Technical University, Bhilai, Chhattisgarh, India
Achal Mishra Drug Design and Discovery Laboratory, Department of Pharmacy, Guru Ghasidas Vishwavidyalaya, Bilaspur-495009, India.
Madhuri Baghel Apollo College of Pharmacy, Affiliated to Chhattisgarh Swami Vivekanand Technical University, Bhilai, Chhattisgarh, India
Mayank Garhewal Drug Design and Discovery Laboratory, Department of Pharmacy, Guru Ghasidas Vishwavidyalaya, Bilaspur-495009, India.
Shekhar Verma Drug Design and Discovery Laboratory, Department of Pharmacy, Guru Ghasidas Vishwavidyalaya, Bilaspur-495009, India.

DOI:

https://doi.org/10.69857/joapr.v14i4.2307

Keywords:

Sirolimus nanodispersion, Drug-layering technology, Prednisolone core tablet, Box–Behnken design, Thrombocytopenia, Fixed-dose combination

Abstract

Background: Thrombocytopenia is a hematological disorder characterized by a reduced platelet count, increasing the risk of bleeding and impairing hemostasis. The present study aimed to develop and optimize a fixed-dose combination tablet comprising a sirolimus nanodispersion layered onto a prednisolone core tablet using a Box–Behnken experimental design as a potential therapeutic strategy for thrombocytopenia. Methodology: Sirolimus nanodispersion drug-layered tablets were prepared and optimized using a three-factor, three-level Box–Behnken design. The optimized formulation was evaluated for critical quality attributes, including hardness and friability, and subsequently experimentally validated. Therapeutic efficacy was investigated in cyclophosphamide-induced thrombocytopenic Wistar rats by assessing platelet count, bleeding time, clotting time, and hematological parameters, including red blood cell count, hemoglobin, and hematocrit. Results and Discussion: The optimized formulation exhibited acceptable mechanical properties, with hardness ranging from 5.3 to 5.5 kg/cm² and friability below 1%, confirming the robustness of the optimization process. In vivo evaluation demonstrated a marked improvement in platelet recovery following treatment. The platelet count increased from 39.87 ± 8.82 × 10³/mm³ in the disease control group to 132.62 ± 21.76 × 10³/mm³ and 154.57 ± 7.40 × 10³/mm³ after once-daily and twice-daily administration, respectively. Furthermore, treatment significantly improved bleeding time, clotting time, and hematological parameters, indicating enhanced therapeutic efficacy. Conclusion: The optimized sirolimus nanodispersion drug-layered prednisolone tablet demonstrated favorable pharmaceutical characteristics and significant therapeutic efficacy in the cyclophosphamide-induced thrombocytopenia model. The developed fixed-dose combination represents a promising formulation strategy for improving the management of thrombocytopenia and warrants further preclinical and clinical investigation.

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