Čes. slov. farm. 2021, 70(6):210-219 | DOI: 10.5817/CSF2021-6-210

Preformulation design of PLGA particulate system for multi-day drug delivery of the antidepressant mirtazapine

Martina Holická^1,*, Jan Muselík¹, Martina Kejdušová¹, Miroslava Pavelková¹, Kateřina Kubová¹, Petr Doležel¹, David Vetchý¹, Vratislav Košťál², Jakub Vysloužil¹, Josef Mašek³

¹ Masaryk University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Brno, Czech Republic

² Tescan Orsay, Brno, Czech Republic

³ Veterinary Research Institute, Department of Pharmacology and Toxicology, Brno, Czech Republic

In this experimental study, the biodegradable polylactide-co-glycolide (PLGA) microparticles (MP) loaded with the insoluble antidepressant mirtazapine were prepared by the simple o/w solvent evaporation method. The formation involved intrinsic variables, such as the content of polymer (700, 900 or 1200 mg), dichloromethane (5 or 10 ml) and/or drug (200 or 400 or 600 mg), and the volume of the aqueous emulsion phase (400, 600 or 800 ml). The influence of these parameters on the size and morphology of microparticles, encapsulation efficiency, and drug release behavior was observed. All MP were successfully prepared, and their size ranged between 165.34 ± 42.88 and 360.17 ± 121.59 μm. MP exhibited prolonged drug release (days), and some profiles had multiphasic character. It was found that the samples prepared with a higher initial amount of PLGA were bigger with prolonged lag time up to 34.3 hours. On the other hand, higher drug concentrations reduced the lag time. The external phase volume reduction and multiplication of dichloromethane amount prolonged the mirtazapine release and decreased the encapsulation efficiency. These observations were further confirmed by multivariate data analysis.

Keywords: microparticles; mirtazapine; PLGA; solvent evaporation method; multivariate data analysis

Grants and funding:

This research was supported by Masaryk University (Project MUNI/A/1574/2020) and the Ministry of Education, Youth and Sports of the Czech Republic (Project CZ.02.1.01/0.0/0.0/15_003/0000495).

Received: July 16, 2021; Accepted: December 3, 2021; Published: June 1, 2021  Show citation