Evaluation of process parameters involved in chitosan microsphere preparation by the o/w/o multiple emulsion method

Objective: The aim of this study is to develop a gastroretentive microsphere of pregabalin using design of experiment (DoE) to decrease dosing frequency and increasing bioavailability. Methods: Pregabalin microsphere was prepared by W/O/O multiple emulsion method using a mixture of ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP) as rate-controlling polymer. Mixed solvent system comprising of dichloromethane (DCM) and acetonitrile (ACN) and light liquid paraffin was chosen as primary and secondary oil phase respectively. Taguchi design was employed for factor screening and Box Behnken design was used for the optimisation of critical process parameters. Results: Taguchi design revealed that polymer: drug, DCM: ACN and PVP: EC is the critical factor for the preparation of microspheres. The optimized formulation was prepared using polymer: drug (4.95:1), DCM: ACN (53.76: 46.24) and PVP: EC (2:5) which showed mean particle size of 203.34±4.82 µm, practical yield of 87.52±2.91 %, encapsulation efficiency of 96.43±3.14 %, floating ability up to 90.42±1.64 % and T60% of 332.81±5.84. Drug release from microsphere followed Higuchi Kinetic model. Conclusion: In a nutshell, microspheres with excellent flowability and great encapsulation efficiency were successfully developed. These can be useful in improving patient compliance by reducing frequent dosing.

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Recent Advance in Polymer Based Microspheric Systems for Controlled Protein and Peptide Delivery

Current Medicinal Chemistry ◽

10.2174/0929867326666190409130207 ◽

2019 ◽

Vol 26 (13) ◽

pp. 2285-2296 ◽

Cited By ~ 20

Author(s):

Yuanyuan Yang ◽

Qiling Chen ◽

Jianyu Lin ◽

Zheng Cai ◽

Guochao Liao ◽

...

Keyword(s):

Protein Delivery ◽

Drug Carriers ◽

Synthetic Polymers ◽

Poly Lactic Acid ◽

Biodegradable Materials ◽

Pharmaceutical Companies ◽

Peptide Drug ◽

Multiple Emulsion ◽

Academic Researchers ◽

Microsphere Preparation

Sustained-release systems made by biodegradable polymers for protein and peptide drug delivery have received considerable attention by academic researchers and major pharmaceutical companies around the world. Various types of biodegradable materials, including natural and synthetic polymers, have been applied to form protein and peptide drug carriers. Among these material candidates, poly lactic acid (PLA) and poly lactic-co-glycolic acid (PLGA) are the most commonly used biodegradable materials in the development of protein and peptide microspheres. In addition, many microsphere preparation technologies, including spray drying, coacervation, multiple emulsion solvent evaporation method and microporous membrane emulsification have been developed for microspheres preparation. In this review, we particularly summarize and briefly introduce the materials and methods that are used to fabricate microspheres as protein delivery systems. The existing opportunities and challenges for successful protein delivery are also discussed.

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