Risperidone Controlled Release Microspheres Based on Poly(Lactic Acid)-Poly(Propylene Adipate) Novel Polymer Blends Appropriate for Long Acting Injectable Formulations

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.

New Biodegradable Poly(l-lactide)-Block-Poly(propylene adipate) Copolymer Microparticles for Long-Acting Injectables of Naltrexone Drug

“…The 1 H-NMR spectra of PLLA, PPAd, and PLLA-b-PPAd copolymers are shown in Figure 3A. The 1 H-NMR spectrum of PPAd, exhibits a triple peak at 4.15 ppm corresponding to methylene group d, a quintuple peak at 1.97 ppm corresponding to methylene group e, a single peak at 2.33 ppm owing to methylene group b and a multiple peak at 1.66 ppm attributed to methylene group c. These peaks have also been documented in previous studies [16,17]. Typical resonance signals were obtained for PLLA, i.e., a quadruple peak at 5.17 ppm attributed to methine group h, and a double peak at 1.6 ppm corresponding to methyl group g. These peaks are in accordance with the literature [19,20].…”

“…As mentioned earlier, the in vivo hydrolysis of PLLA is slow and hence time-consuming [29]. It is thus a common practice to evaluate the hydrolytic degradation in the presence of enzymes [17]. More specifically, in the present work, the enzymatic hydrolysis of PLLA, PPAd and their copolymers was studied using a mixture of Rhizopus oryzae and Pseudomonas cepacia lipases.…”

“…PLLA-b-PPAd copolymers were synthesized by a combination of melt polycondensation and ring-opening polymerization, as described in Figure 1. Initially, poly(propylene adipate) (PPAd) homopolymer was synthesized by a two-stage melt polycondensation method [16,17]. Briefly, during esterification (1st stage), PPAd oligomers were synthesized and water was removed as a byproduct.…”

“…Polymers 2020, 12, x FOR PEER REVIEW 17 of 24 17.2°, and the presence of NTX could affect its structure. In microparticles prepared with PPAd it seems that a semicrystalline formulation was obtained mainly ought to the polymer rather than NTX.…”

Hierarchical Porous Carbon—PLLA and PLGA Hybrid Nanoparticles for Intranasal Delivery of Galantamine for Alzheimer’s Disease Therapy

“…Alzheimer's disease (AD) is one of the major causes of senile dementia and is characterized by progressive neurodegeneration that causes gradual neuronal and memory loss, as well as cognition impairment [1]. The ever-growing prevalence of AD and its detrimental effect on patients' quality of applications [16][17][18][19][20]. Furthermore, poly(lactide-co-glycolide) (PLGA), with lactide:glycolide ratios of 75/25 and 50/50 w/w has already been studied in microparticle preparation with paclitaxel [21] or paliperidone [22,23], an anticancer and an antipsychotic drug, respectively, either alone or by absorbing the drugs on silica-based nanoparticles (SBA-15 and MCF).…”