Dhrubojyoti Mukherjee1, Bharath Srinivasan1, J Anbu2, Mohammad Azamthulla2, Venkatesh Teja Banala3, S G Ramachandra4. 1. a Department of Pharmaceutics , M. S. Ramaiah University of Applied Sciences , Bengaluru , India. 2. b Department of Pharmacology , M. S. Ramaiah University of Applied Sciences , Bengaluru , India. 3. c Pharmaceutics Department , Central Drug Research Institute , Lucknow , India. 4. d Central Animal Facility , Indian Institute of Science , Bengaluru , India.
Abstract
OBJECTIVE: In this study, we investigated the potential of thiolated chitosan-based mucoadhesive film, loaded with risedronate sodium in the treatment of osteoporosis. SIGNIFICANCE: Risedronate sodium is a bisphosphonate derivative having very low bioavailability when administered through the oral route. Moreover, the adverse effects associated with the drug when administered through GIT necessitate an alternative and feasible route which can improve its bioavailability and therapeutic efficacy. METHODS: Thiolation of chitosan was interpreted by different analytical techniques. The mucoadhesive films were prepared by the solvent evaporation method and evaluated for drug content analysis, swelling degree, mucoadhesive parameters, and permeation characterization. For the screening of preclinical efficacy and pharmacodynamic parameters, a methylprednisolone induced osteoporotic rat model was used. The trabecular microarchitecture and biochemical markers were evaluated for determination of bone resorption. RESULTS: The different analytical characterization of synthesized thiolated chitosan revealed that chitosan was successfully incorporated with thiol groups. The formulation containing 2:1 ratio of thiolated chitosan and HPMC-4KM was found to have the maximum swelling degree, mucoadhesive strength with a good force of adhesion and better in vitro permeability compared to the marketed formulation. With respect to trabecular microarchitecture, the drug-loaded film formulation showed superior and promising results. Furthermore, the film formulation also improved the serum level of biomarkers better than the marketed formulation. CONCLUSIONS: The results significantly suggest that risedronate loaded novel mucoadhesive film formulation could be a logical approach in the therapeutic intervention of osteoporosis.
OBJECTIVE: In this study, we investigated the potential of thiolated chitosan-based mucoadhesive film, loaded with risedronate sodium in the treatment of osteoporosis. SIGNIFICANCE: Risedronate sodium is a bisphosphonate derivative having very low bioavailability when administered through the oral route. Moreover, the adverse effects associated with the drug when administered through GIT necessitate an alternative and feasible route which can improve its bioavailability and therapeutic efficacy. METHODS: Thiolation of chitosan was interpreted by different analytical techniques. The mucoadhesive films were prepared by the solvent evaporation method and evaluated for drug content analysis, swelling degree, mucoadhesive parameters, and permeation characterization. For the screening of preclinical efficacy and pharmacodynamic parameters, a methylprednisolone induced osteoporoticrat model was used. The trabecular microarchitecture and biochemical markers were evaluated for determination of bone resorption. RESULTS: The different analytical characterization of synthesized thiolated chitosan revealed that chitosan was successfully incorporated with thiol groups. The formulation containing 2:1 ratio of thiolated chitosan and HPMC-4KM was found to have the maximum swelling degree, mucoadhesive strength with a good force of adhesion and better in vitro permeability compared to the marketed formulation. With respect to trabecular microarchitecture, the drug-loaded film formulation showed superior and promising results. Furthermore, the film formulation also improved the serum level of biomarkers better than the marketed formulation. CONCLUSIONS: The results significantly suggest that risedronate loaded novel mucoadhesive film formulation could be a logical approach in the therapeutic intervention of osteoporosis.