DEVELOPMENT OF BIOPROTECTIVE IN SITU IMPLANTS OF OLANZAPINE: EFFECT OF HYDROPHOBIC SOLVENT
DOI:
https://doi.org/10.22159/ijap.2026v18i3.57879Keywords:
Schizophrenia, Medication non-adherence, In situ implants, Olanzapine, Hydrophobic solventAbstract
Objective: Medication non-adherence is a major contributor to therapeutic failure in schizophrenia, often resulting in relapse, hospitalization, and increased mortality. Olanzapine, a first-line antipsychotic, undergoes extensive first-pass metabolism after oral administration, reducing its long-term therapeutic effectiveness. This study aimed to develop and optimize a Quality by Design (QbD)-based olanzapine-loaded in situ implant (O-ISI) to improve medication adherence, minimize the initial burst release, and provide sustained drug delivery.
Methods: O-ISI formulations were prepared using poly(lactic-co-glycolic acid) (PLGA) and a mixed solvent system comprising dimethyl sulfoxide (DMSO) and benzyl benzoate. A D-optimal experimental design was employed to evaluate the effect of polymer concentration (A), DMSO:benzyl benzoate ratio (B), and lactic acid content in PLGA (C) on initial burst release (R1) and percentage drug release at 30 days (R2). In vitro drug release studies were conducted to assess formulation performance.
Results: Among the developed formulations, O-ISI-7 exhibited the lowest initial burst release (5.16%) with 26.09% drug release on day 30, whereas O-ISI-2 showed the highest burst release (28.62%) and 99.91% drug release at day 30. The optimized formulation containing 40% PLGA with 75% lactic acid and a DMSO:benzyl benzoate ratio of 1:1.7 demonstrated controlled drug release with an initial burst of 7.15% and 25.72% release over 30 days.
Conclusion: The optimized formulation demonstrated sustained drug release with reduced initial burst release. The novelty of this study lies in the use of benzyl benzoate as a hydrophobic solvent in a PLGA-based in situ implant system, which effectively modulates phase inversion behavior and minimizes burst release while maintaining controlled drug release kinetics. Further in vivo studies are planned to establish in vitro–in vivo correlation and confirm safety and efficacy.
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