Abstract
Objective: The aim of the present study was to optimize long-acting injectable (LAI) microspheres of Paliperidone palmitate (PP) for treatment of schizophrenia using face-centered central composite design (FC-CCD). Methods: In this study, poly lactic-co-glycolic acid (PLGA) based LAI microspheres of paliperidone palmitate (PP) were formulated by using FC-CCD. LAI microspheres were developed by using oil in water (O/W) emulsion solvent evaporation technique. On the basis of preliminary trials, FC-CCD was employed to check effect of independent variables such as drug polymer ratio (X1), homogenization speed (X2) and rate of addition (X3). While mean particle size (Y1), drug loading (Y2), entrapment efficiency (Y3), burst release (Y4), and drug release on day 60 (Y5) were considered as dependent variables and statistically evaluation performed by using design expert 12 software. Morphology of prepared microspheres was studied by using the scanning electron microscopy (SEM) technique, while particle size was analyzed by laser diffraction technique. In vitro drug release studies were performed using a controlled temperature shaking water bath apparatus. Fourier transforms infrared spectroscopy (FTIR) and differential scanning calorimetric (DSC) study were performed to analyze any changes in crystal behavior or to detect any chemical bonding between ingredients. 13C NMR and 1H NMR techniques were used to analyze end-capping and monomer ratio in developed microspheres. Results: The factorial batches mean particle size was found to be 38 µm to 104 µm and drug loading were found between 27.2 % to 47.2%. Mathematical modelling of drug release kinetics revealed that near zero-order drug release of checkpoint formulations. Endcap analysis and molar ratio of formulated microspheres were found to be ester end cap and ~75:25, respectively. Morphologically all the prepared samples were found to be spherical in shape and smooth surface. FTIR data showed no significant interactions occurred between drug and excipients. The actual responses of checkpoint formulations were observed within 5% variation of predicted values. Conclusion: The prepared microspheres showed promising results of morphology, particle size, drug loading, entrapment efficiency, burst release and drug release on day 60. The successful predictive designs models were achieved from employed FC-CCD.
Highlights
Long-acting injectable (LAI) dosage forms are becoming choice of medical practitioners to combat diseases which need long-term therapy for management and cure [1]
Composition and manufacturing process parameters were observed to show an impact on the particle size and particle size distribution of prepared microspheres
The responses obtained from seventeen formulation runs were showed strong effect of independent process variables on formation of Paliperidone palmitate (PP) microspheres
Summary
Long-acting injectable (LAI) dosage forms are becoming choice of medical practitioners to combat diseases which need long-term therapy for management and cure [1]. LAI’s are being used for clinical management of various disease conditions like cancer, schizophrenia, opioid intolerance; diabetes, acromegaly, osteoarthritis etc [2]. Continuous research is ongoing to cater the unmet need of medical field for newer disease conditions and dosage designs. Schizophrenia is mental disorder that adversely affects thoughts and daily life of patient. Schizophrenia is associated with impact on health, social, occupational, and economics. Hostility, depression and body mass index may be targeted to improve quality of life [11]
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