Abstract
The present study evaluates the preparation of risperidone controlled release microspheres as appropriate long-acting injectable formulations based on a series of novel biodegradable and biocompatible poly(lactic acid)–poly(propylene adipate) (PLA/PPAd) polymer blends. Initially, PPAd was synthesized using a two-stage melt polycondensation method (esterification and polycondensation) and characterized by 1H-NMR, differential scanning calorimetry (DSC), and powder X-ray diffraction (XRD) analyses. DSC and XRD results for PLA/PPAd blends (prepared by the solvent evaporation method) showed that these are immiscible, while enzymatic hydrolysis studies performed at 37 °C showed increased mass loss for PPAd compared to PLA. Risperidone-polyester microparticles prepared by the oil–water emulsification/solvent evaporation method showed smooth spherical surface with particle sizes from 1 to 15 μm. DSC, XRD, and Fourier-transformed infrared (FTIR) analyses showed that the active pharmaceutical ingredient (API) was dispersed in the amorphous phase within the polymer matrices, whereas in vitro drug release studies showed risperidone controlled release rates in all PLA/PPAd blend formulations. Finally, statistical moment analysis showed that polyester hydrolysis had a major impact on API release kinetics, while in PLA/PPAd blends with high PLA content, drug release was mainly controlled by diffusion.
Highlights
Drug parenteral administration is the main choice of treatment especially in cases where the active pharmaceutical ingredient (API) exhibits high first-pass metabolism, is highly unstable in the gastrointestinal physiological conditions or shows a narrow therapeutic index
Risperidone release from prepared microspheres followed two-step release kinetics, i.e., an initial burst release phase, observed up to approximately six hours, and a controlled release phase which lasted till the end of dissolution process
Dissolution results showed that microspheres consisting of neat PPAd release up to 95% of the API within the first three days of dissolution, while at the same time only the 40% of the API is released by neat poly(lactic acid) (PLA) microspheres
Summary
Drug parenteral administration is the main choice of treatment especially in cases where the active pharmaceutical ingredient (API) exhibits high first-pass metabolism, is highly unstable in the gastrointestinal physiological conditions or shows a narrow therapeutic index. In order to overcome these, the reduction of the total number of injections through the use of properly designed depot controlled release parenteral formulations has shown to be truly advantageous, especially in cases where long-term treatment is needed [1,2,3,4]. Research on such drug delivery systems has been growing increasingly in the last decades due to the several advantages that they possess, including better patient compliance through lower dosing frequency, consistent drug blood levels, reduced adverse effects, avoidance of first-pass metabolism etc. Drug release from such systems is governed by simultaneous drug diffusion and polymer erosion [20,21]
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