Title:A Quality By Design (QbD) Prospect in Fabrication of PLGA-based
Antipsychotic Long-acting Microspheres: An Alternative to Combination
Therapy
Volume: 7
Issue: 1
Author(s): Akanksha Singh, Rajkiran Narkhede and Rajani Athawale*
Affiliation:
- Prin. K. M. Kundnani College of Pharmacy, Cuffe Parade, Mumbai, 400 005, India
Keywords:
Risperidone, antipsychotic, PLGA, quality by design (QbD), TEM, SEM.
Abstract:
Background: Discontinuation and poor compliance with long-term oral medicine are
major therapeutic issues in psychosis treatment. Poorer long-term outcomes may result from
non-compliance as well as a higher chance of relapse. In order to sustain therapeutic drug plasma
levels, co-administration of oral antipsychotics is necessary for commercially available longacting
injections of second-generation antipsychotics, as they have a lag period of approximately
three weeks during the drug release process.
Methods: Poly(lactic-co-glycolic acid) (PLGA) encapsulated microspheres loaded with risperidone
were fabricated in the current research for intramuscular administration. The single emulsion
solvent evaporation technique was applied for the fabrication of microspheres. Risperidone
microspheres were prepared using PLGA grade 75:25. Particle size, drug content and entrapment
efficiency with a central composite design were the main optimization parameters for the formulation.
The microspheres were characterized by different techniques, namely Fourier transform
infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry
(XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The
drug content, entrapment efficiency, morphology, particle size, and in vitro release profiles,
along with release kinetics of the risperidone microspheres, were studied.
Results and Discussion: The microspheres produced by the single emulsion solvent evaporation
approach show smooth and spherical morphology, with particle size ranging from 3 μm to 6 μm,
drug content of 99.7%, and entrapment efficiency of 98.2% with little burst release of 3% to
10%, providing drug release for 45 days and exhibiting zero order release kinetics and Korsmeyer-
Peppas model for non-fickian drug release from the polymeric matrix. By applying the Quality
by Design (QbD) approach and formulation parameters, microspheres with appropriate particle
size, morphology, enhanced drug content, entrapment efficiency and desirable drug release
profile for depot formulation can be obtained successfully.
Conclusion: The optimized microspheres, in comparison to the marketed Risperdal Consta™,
show enhanced potential for a better depot formulation, which can further improve patient compliance.
