Title:Formulation and Characterization of Phytosomes as Drug Delivery System
of Formononetin: An Effective Anti-Osteoporotic Agent
Volume: 21
Issue: 2
Author(s): Arun Agarwal, Muhammad Wahajuddin*, Swati Chaturvedi, Sandeep K. Singh, Mamunur Rashid, Richa Garg, DIvya Chauhan, Nazneen Sultana and Jiaur R. Gayen
Affiliation:
- Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow-226031, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India
- Institute of Cancer Therapeutics,
School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Richmond Road, Bradford
BD7 1DP, United Kingdom
Keywords:
Formononetin, phospholipid complex, solubility, pharmacokinetic study, first-pass metabolism, sprague dawley rat.
Abstract:
Background: Formononetin (FNT), a methoxy isoflavone, is a potential phytoconstituent
utilized for refurbishing fractures in bone tissue. Conceding to its involvement in first-pass metabolism
followed by glucuronidation, its absorption efficacy is limited. Hence, it belongs to the BCS class II
classification.
Objective: We designed the present work to enhance FNT oral bioavailability by using Phospholipids
(PL) as a promising carrier. Formononetin Phospholipid Complex (FNT-PC) was prepared by the solvent
evaporation method and characterized.
Methods: FNT-PC was prepared by solvent evaporation method and characterization (FNT-PC) was
performed using aqueous/n-octanol solubility and partition coefficient, FTIR, NMR, SEM, and in vivo
pharmacokinetic study in female SD rats at 50 mg/kg.
Results: Physicochemical properties like aqueous/n-octanol solubility and partition coefficient were
enhanced in FNT-PC. The FTIR spectrum confirmed there was no involvement of functional groups in
the preparation of FNT-PC. Whereas, the NMR study resulted in the attachment of carbon (C-8) position
of FNT by replacing the quaternary amine of PL to form FNT-PC. When scrutinized for its surface
morphology, the FNT-PC exhibited the amorphous geometry that remarkably enhanced the dissolution
of FNT (p<0.05) from its pure form. This dissolution effect was also affirmed by the per-oral administration
of FNT-PC in female Sprague Dawley (SD) rats at 50 mg/kg dose. The pharmacokinetic profile
showed the free FNT levels were markedly increased, correspondingly decreasing the conjugated
FNT levels in rat plasma.
Conclusion: To summarize, FNT-PC could substantially reduce the first-pass metabolism with enhanced
free concentration, improving oral bioavailability for therapeutic use.