Development of polymeric nanoparticles with highly entrapped herbal hydrophilic drug using nanoprecipitation technique: an approach of quality by design

Abstract

The intention of this study is to achieve higher entrapment efficiency (EE) of berberine chloride (selected hydrophilic drug) using nanoprecipitation technique. The solubility of drug was studied in various pH buffers (1.2–7.2) for selection of aqueous phase and stabilizer. Quality by design (QbD)-based 3² factorial design were employed for optimization of formulation variables; drug to polymer ratio (X₁) and surfactant concentration (X₂) on entrapment efficiency (EE), particle size (PS) and polydispersity index (PDI) of the nanoparticles. The nanoparticles were subjected to solid state analysis, in vitro drug release and stability study. The aqueous phase and stabilizer selected for the formulations were pH 4.5 phthalate buffer and surfactant F-68, respectively. The formulation (F-6) containing drug to polymer ratio (1:3) and stabilizer (F-68) concentration of 50 mM exhibited best EE (82.12%), PS (196.71 nm), PDI (0.153). The various solid state characterizations assured that entrapped drug is amorphous and nanoparticles are fairly spherical in shape. In vitro drug release of the F-6 exhibited sustained release with non-Fickian diffusion and stable at storage condition. This work illustrates that the proper selection of aqueous phase and optimization of formulation variables could be helpful in improving the EE of hydrophilic drugs by nanoprecipitation technique.

• Berberine chloride
• hydrophilic drug
• nanoprecipitation
• poly (ɛ-caprolactone)
• QbD

Acknowledgements

The first author gratefully acknowledges the Indian Council of Medical Research and Special Assistance Program of University Grants Commission, New Delhi, India for providing of financial assistance in the form of Senior Research Fellowship and Instrumentation facility, respectively. Authors are thankful to Dr. Madhu Yashpal, Department of Anatomy, Institute of Medical Sciences for TEM study. The authors also thankfully acknowledge M/s. Inga Pharma, Mumbai, India, for generous supply of Berberine Chloride.

Declaration of interest

The authors state no conflict of interest.