Polymer-based prolonged-release nanoformulation of duloxetine: fabrication, characterization and neuropharmacological assessments

Abstract

Objective

The poly D, L–Lactic-co-glycolic acid (PLGA) and Polycaprolactone (PCL) have been widely applied for developing the prolonged-release formulation. The current study explores the application of these polymers for developing prolonged-release nanosphere of Duloxetine (DLX). Developing a prolonged release parenteral nanosphere formulation of DLX would be overcoming pitfalls like acid-labile degradation, first-pass metabolism and erratic bioavailability along with long-term therapeutic benefit in the treatment of depression.

Methods

DLX-loaded PLGA and PCL nanospheres were prepared by using the emulsion solvent evaporation technique. The developed formulation was compared with DLX oral solution concerning brain estimation. The prepared nanospheres were subjected to the morphology of the drug particles, polydispersity Index (PDI), distribution size, zeta potential, entrapment efficiency and percentage yield to generate a proof of concept.

Results

DLX-loaded polymeric nanosphere exhibited the uniform size from 89.48 nm to 100.9 nm. The entrapment efficiency was in the range of 74.93 to 77.49, respectively, of PLGA and PCL formulation. The FSEM image affirmed smooth spherical morphology. A good PDI and negative zeta potential value (−31.3 mV for F1 and −30.7 mV for F2) supported the stability of the nanosphere. The brain concentration of the drug was three times enhanced supporting the effectiveness of the nanosphere during pharmacodynamic and pharmacokinetic studies.

Conclusion

The intramuscular DLX-loaded nanospheres signify improved brain availability relative to DLX solution. This can be a blueprint for the effective and targeted brain delivery of CNS drugs.

Keywords:

• Nanospheres
• duloxetine
• long acting parenteral
• PLGA
• PCL

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by Indian Council of Medical and Research (ICMR), New Delhi under grant number 45/57/2015/PHA-BMS. Authors would like to acknowledge, Faculty of Pharmacy, Panjab University for FTIR and DSC analysis and Faculty of Sophisticated Analytical Instrumentation Facility, Panjab University for FeSEM and XRD analysis.