Polymer Erosion Research Articles

Moringa oleifera protein isolates as novel wall materials in the encapsulation of limonene: Physicochemical properties and its stability

The purpose of this study was to investigate the efficiency of Moringa oleifera protein isolates (MPI) as a wall material for encapsulating limonene. MPI (10 % concentration) formed stable emulsions with a mean droplet size of 1.63±0.07 μm and viscosity of 3.54±0.10 mPa·s. Characterization of microcapsules revealed encapsulation efficiency (94.77±0.05 %), yield (56.50±5.07 %), aqueous solubility (21.00±0.92 %), water activity (0.46±0.01), moisture (2.09±0.42 %), a light color, indicating suitability for incorporation into food products. MPI better protected limonene from light and temperature compared with soy protein isolate (SPI), commonly used in encapsulation. The Korsmeyer-Peppas model best fit the release behavior of MPI-limonene microcapsules (r2=0.959), indicating that the release was controlled by relaxation of polymer chains and erosion. The release constant (k0) implied that MPI (2.303) had a faster release rate of limonene than SPI (1.997). The findings indicate that MPI is a potential wall material for limonene encapsulation, with promising physicochemical properties and improved oxidative stability.

Measuring Erosion of Biodegradable Polymers in Brimonidine Drug Delivery Implants by Quantitative Proton NMR Spectroscopy (q-HNMR)

Erosion of biodegradable polymeric excipients, such as polylactic acid (PLA) and polylactic-co-glycolic acid (PLGA), is generally characterized by microbalance for the remaining mass of PLA and/or PLGA and Gel Permeation Chromatography (GPC) for molecular weight (MW) decrease. For polymer erosion studies of intravitreal sustained release brimonidine implants, however, both microbalance and GPC present several challenges. Mass loss measurement by microbalance does not have specificity for excipient polymers and drug substances. Accuracy of the remaining mass by weighing could also be low due to sample mass loss through retrieval-drying steps, especially at later drug release (DR) time points. When measuring the decrease of polymer MW by GPC, trace amounts of polymeric degradants (oligomers and/or monomers) trapped inside the implants during DR tests may not be measurable due to sensitivity limitations of the GPC detector and column MW range. Previous efforts to measure remained PLGA weight of dexamethasone micro-implants using qNMR with external calibration have been performed, however, these measurements do not account for chemical structure changes (i.e. LA to GA ratio changes from time zero) of PLGA implants during drug release tests. Here, a qNMR method with an internal standard was developed to monitor the following changes in micro-implants during drug release tests: 1. The remaining overall PLA/PLGA mass. 2. The remaining lactic acid (LA), glycolic acid (GA) unit and PLGA's lauryl ester end group percentages. 3. The trace content of PLA/PLGA oligomers as degradants retained in the implants. Unlike microbalance analysis, qNMR has both specificity for drug substance, excipient polymer, and accuracy due to minimal implant loss during sample preparation. Compared to the overall PLA/PLGA remaining mass generally monitored in erosion studies, the percentage of remaining LA, GA, and the ester end group provide more information about the microstructure change (such as hydrophobicity) of PLA/PLGA. Additionally, the qNMR method can complement GPC methods by measuring the change of remaining PLA and PLGA oligomer concentrations in brimonidine implants, with tenfold less sample and no MW cutoff. The qNMR method can be used as a sensitive tool for both polymer excipient characterization and kinetics studies of brimonidine implant erosion.

Targeted therapy of gastric cancer with gingerol-loaded hyaluronic acid/PEG-coated PLGA nanoparticles: Development and physicochemical evaluation

In recent years, nanoparticle (NP)-based drug delivery systems have emerged as promising candidates for targeted therapy due to their ability to enhance drug bioavailability and delivery of therapeutic agents to tumor sites. Herein, we aim to develop gingerol-hyaluronic acid (HA)-poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-NPs (gingerol-HA-NPs) as a targeted therapy for gastric cancer. To target the CD44 receptor expressed on malignant cells, gingerol-HA-NPs were fabricated using a single-emulsion solvent evaporation method. The physicochemical properties and cytotoxicity of the NPs were characterized, and their cellular uptake was assessed using flow cytometry analysis. Flow cytometry analysis of FITC-labeled annexin V/PI-stained cells was used to evaluate the induction of apoptosis/necrosis by the NPs. In vitro release studies demonstrated sustained and controlled release of gingerol from the NPs over 72 h. The release kinetics followed the Peppas-Korsmeyer model, suggesting that drug release was influenced by polymer erosion and disentanglement. Also, the NPs showed dose-dependent cytotoxic effects on MKN cells, with lower IC50 values than plain gingerol. The IC50 values for gingerol-PLGA-PEG-NPs (gingerol-NPs) and gingerol-HA-NPs were 175 μM and 117 μM, respectively after 48 h, while the IC50 value for plain gingerol was 202 μM. Gingerol-HA-NPs exhibited higher cellular uptake in MKN cells (CD44+) compared to plain drug and gingerol-NPs. The uptake increased with prolonged incubation. The analysis of apoptosis/necrosis detection showed that the gingerol-HA-NPs caused a greater occurrence of late apoptosis (An+/PI+) in MKN cells compared to plain gingerol and gingerol-NPs, with percentages of 76.43 %, 11.58 %, and 24.03 % respectively. These results underscore the potential of gingerol-HA-NPs as a promising targeted therapy for the treatment of gastric cancer.

Modification of the swelling behavior of a hydrophilic polymer as an approach to maintaining a constant gel layer thickness

The objective of the present study was to screen some ionic polymers that can modify the swelling and erosion characteristics of a hydrophilic polymer (HPMC) and thereby help provide constant drug release. It was hypothesized that the hydrophilic polymer's swelling rate and erosion of matrices could be modified by adding an ionic polymer, as the two will form a hydrogen bond. Methocel™ K4M (HPMC) was selected as the hydrophilic polymer. NaCMC, Eudragit® S100, and Eudragit® L100 were selected as anionic polymers. Eudragit® RSPO, Eudragit® RLPO and Eudragit® EPO were selected as cationic polymers. Various techniques were used to characterize the rate of swelling, gel layer thickness, and erosion of matrices of HPMC-ionic polymer combinations (3:1 ratio). Fourier-transform infrared spectroscopy was used to study HPMC-ionic polymer interaction. A texture analyzer was used to investigate the change in gel layer thickness and firmness of matrices during dissolution study over time. The stereo microscopic examination provided a structural change in matrices during swelling. Of all the matrices, the HPMC-Eudragit® RSPO combination showed simultaneous swelling and matrix erosion, resulting in constant gel layer thickness (diffusional path length) for 12 h.

Preparation, Characterization and in vitro/vivo Evaluation of Long-Acting Rivaroxaban-Loaded Microspheres.

Rivaroxaban is widely used for long-term prevention and maintenance therapy of thromboembolic disorders. The existing oral dosage forms of rivaroxaban lead to poor patient adherence because of repeated daily administration. The aim of this study is to design long-acting rivaroxaban- loaded microspheres to reduce dosing frequency and improve patient compliance. Rivaroxaban-loaded microspheres were prepared using the emulsion-solvent evaporation method. The microspheres were evaluated in terms of morphology, particle size, drug loading and encapsulation efficiency, the physical state of the drug in the matrix, in vitro release/release mechanism, and in vivo pharmacokinetics in Sprague Dawley rats. Rivaroxaban-loaded microspheres presented spherical-shaped particles displaying a mean particle size of 89.3 μm, drug loading of 16.5% and encapsulation efficiency of 97.8%. The X-ray diffraction indicated that rivaroxaban existed in crystal form in the microspheres. in vitro release lasting approximately 50 days was characterized as a tri-phasic pattern: (1) an initial burst release, mainly due to the dissolution of drug particles with direct access to the microparticles' surface, (2) a "plateau" phase with a slow-release rate controlled by the diffusion and (3) a final, rapid drug release phase controlled by polymer erosion. Pharmacokinetic studies showed that rivaroxaban microspheres maintained a sustained release for more than 42 days. Rivaroxaban-loaded microspheres have great potential clinical advantages in reducing dosing frequency and improving patient compliance. The data obtained from this study could be used as scientific evidence for decision-making in future formulation development.

Hydrophilic polymer based oral formulations studied by NMR relaxometry and UTE MRI - towards polymer mobilization and erosion assessment

Hydrophilic polymer based oral formulations studied by NMR relaxometry and UTE MRI - towards polymer mobilization and erosion assessment

PULSATILE DRUG DELIVERY: A STRATEGY FOR TREATING CHRONOTHERAPEUTIC AILMENTS

Modern drug delivery systems have been promoted to a unique notion of chronopharmacology, i.e., the ability to provide the medicament to a patient in a staggered profile, as the discipline of chronobiology has advanced. The main disadvantage of developing such a delivery system that fits the circadian cycle is the lack of accurate technology (Pulsatile drug delivery system, PDDS). Pulsatile devices are gaining popularity because they deliver the medicine to the correct region of action at the correct time, allowing for spatial and temporal dosing and compliance among patients. These technologies are meant to work with the body's natural circadian cycle. The circadian rhythm affects various biological systems in humans, including metabolism, physiology, behaviour, sleep patterns, hormone synthesis, and so on. This article addresses several methods, such as osmotic systems, capsular systems, single and multiple-unit programable devices that rely on soluble or erodible polymer coatings, and the usage of rupturable membranes. The present review covered the rationale for the creation of pulsatile drug delivery systems, benefits, limitations the types of diseases that require pulsatile release, categorization, and assessments of pulsatile system of drug delivery.

Hydrogen-Bonding Induced Crosslinked Polymer Network for Highly Stable Electrochromic Device and a Construction Strategy for Black-Bilayer Electrochromic Film.

This work presents a new strategy to achieve highly stable electrochromic devices and bilayer film construction. A novel solution-processable electrochromic polymer P1-Boc with quinacridone as the conjugated backbone and t-Boc as N-substituted non-conjugated solubilizing groups is designed. Thermal annealing of P1-Boc film results in the cleavage of t-Boc groups and the formation of N─H⋯O═C hydrogen-bonding crosslinked network, which changes its intrinsic solubility characteristics into a solvent-resistant P1 film. This film retains the electrochemical behavior and spectroelectrochemistry properties of the original P1-Boc film. Intriguingly, the electrochromic device based on the P1 film exhibits an ultrafast switching time (0.56/0.80 s at 523nm) and robust electrochromic stability (retaining 88.4% of the initial optical contrast after 100000 cycles). The observed cycle lifetime is one of the highest reported for all-organic electrochromic devices. In addition, a black-transparent bilayer electrochromic film P1/P2 is developed in which the use of the solvent-resistant P1 film as the bottom layer avoids interface erosion of the solution-processable polymer in a multilayer stacking.

Surface Eroding Methacrylic Anhydride Copolymers and Model Drug Release

AbstractMethacrylic anhydride (MAA)‐based copolymers are synthesized to probe how comonomer composition and type affect the erosion profiles. Anhydrides readily undergo hydrolysis, which when combined with high crosslink density and hydrophobicity tend to exhibit an ideal surface erosion mechanism for drug delivery, tissue adhesives, and biocement applications. The cylindrical (10 mm diameter × 5 mm height) polyanhydrides are degraded under pseudo‐physiological conditions and surface erosion is qualitatively observed via photographs. The non‐anhydride comonomer can be utilized to tune erosion profiles while retaining degradability and product solubility. The comonomer can accelerate or slow the degradation process to a greater extent at low MAA concentrations. Drug release is conducted using purpurin to model hydrophobic drugs. Purpurin concentration is quantified using UV–visible spectral analysis. Purpurin extends the degradation profile due to a combination of local pH changes, hydrophobicity, and molecular diffusion. Linear purpurin release is observed as a function of polymer erosion (0.9897 R2) thus confirming a surface erosion‐mediated drug release mechanism.

Controlled release of bilayer tablet comprising vitamin B6 rapid-release layer and melatonin sustained-release layer

Here, the formulation of a novel bilayer tablet comprising a vitamin B6 rapid-release layer and a melatonin sustained-release layer is described. The effects of viscosity and concentration of the sustained-release matrix material, amount of diluent, and melatonin particle size on the release characteristics of melatonin were examined. In addition, the drug-release behavior of the prepared bilayer tablets was examined in different dissolution media. Further, drug-release kinetics and melatonin behavior in the sustained-release layer were evaluated based on dissolution profiles and changes in tablet weight during dissolution. Furthermore, the stability of the bilayer tablet was established. The in vitro release test revealed that vitamin B6 was completely released within 10–15 ​min, with melatonin demonstrating ∼90% cumulative release within 8 ​h. Based on kinetic model fitting results, melatonin release was well fitted to the Ritger-Peppas model; the release mechanism was non-Fick diffusion with both diffusion and erosion. The drug-release study confirmed that the melatonin sustained-release layer predominantly underwent polymer swelling rather than polymer erosion. The stability test results showed that the bilayer tablets had good stability under high temperature, high humidity, and light conditions. The bilayer tablets offer an alternative for the controlled-release oral administration of melatonin, although their in vivo effects need to be investigated in human studies.

Exploration, Development and Optimization of Eco-friendly Novel Dosage Form – Pastilles

Background: Now-a-day, there is the need to explore the concept of green chemistry in every field. Many existing conventional and novel drug delivery systems have problems related to green chemistry. To overcome the existing limitations of the different dosage forms, a newer untouched dosage form pastilles was explored. Objective: The present study aims to optimize the Glipizide (GPZ) matrix pastilles using waxy erodible polymers integrating the concept of quality by design (QbD) and green chemistry. Methods: The pastilles were formulated using the fabricated lab-scale pastillator. GPZ was used as a model drug. The concern related to the drug is low aqueous solubility and short variable half-life. The solubility of the drug was improved by formulating a complex between GPZ and chemically modified ß –cyclodextrin (β-CD) - hydroxypropyl-ß-cyclodextrin (HP- ß -CD). The complex was prepared using the kneading method. The complex was formulated incorporated different stoichiometric ratios of GPZ: complexing agent. Sustained-release pastille formulated using Gelucire 43/01 (GC 43/01) as release retardant polymer. The central composite design had been used to obtain an optimum batch, using the amount of GC 43/01 and temperature as independent variables, while drug release at 2h, 6h, and 10h was chosen as dependent variables. Design batches were evaluated for post-and preformulation parameters. An optimum formulation was evaluated for the influence of hydroalcoholic media on drug release. Results: The complex formulated using HP- ß –CD (1:1) shown better solubility (36.5mg/ml) and dissolution. The complex was incorporated in the pastilles with erodible polymer GC 43/01. The formulation was found robust with optimum pre and post formulation parameters. Optimized batch was chosen from the design space of central composite design. The drug release of the optimized formulation was found 29.13%, 57.29% and 85.70% at 2, 6 and 10 hrs respectively which was similar to the drug release of the marketed formulation. As the amount of alcohol increased from 5 to 40 %, the drug release also increased but did not show a dose dumping effect. It is just due to the altered solubility of GPZ in alcohol. Conclusion: The untouched formulation, Pastilles of GPZ were developed incorporating the waxy erodible polymer. Pastilles were capable to control drug release up to 12 h. The amount of GC 43/01 and temperature had a significant effect on the formulation of GPZ sustained-release pastille. The newer approach of formulating pastilles might apply to the industry as it is an eco-friendly, single-step process and uses fewer excipients.

Formulation and Evaluation of Aspirin-PLGA Microsphere for the Dental Stem Cell Stimulation

Abstract: Aim: According to WHO, dental caries is the most prevalent oral disease, and its progression leads to tooth loss. Clinical management of caries focuses on the severity and extent of disease with the main aim, i.e., the ‘art’ of creating a good restoration. Recently, it has been reported that aspirin can stimulate existing stem cells and regenerate damaged teeth. But, the therapeutic effectiveness of a drug depends on developing a suitable novel drug delivery system, to retain at the site and suitably release the drug to produce effective therapy. Therefore, the present investigation intends to develop Aspirin-Poly lactic-co-glycolic acid microspheres for the restoration of dentin. Materials and Methods: Aspirin- Poly lactic-co-glycolic acid microsphere was formulated by the double emulsion technique and evaluated for particle size, encapsulation efficiency, characterization (differential scanning calorimetry, X-ray powder diffraction), in vitro release, as well as irritation testing using the Hen’s egg test-chorioallantoic membrane method. Results: The formulation exhibited good encapsulation efficiency (87.31±1.52%) and a particle size of 7.52 μm by Scaning Electron Micrscopy. In vitro release study exhibited sustained release (98.76±0.49%) for 16 days and triphasic release. This confirms that release is due to polymer erosion, swelling, and degradation. The ex vivo permeation study also confirmed sustained permeation and showed the significant partition and accumulation of the drug in the tissue. Further, the prepared formulation showed significantly low irritation compared to positive control by Hen’s Egg Test-Chorioallantoic Membrane method. Conclusion: Thus, the above finding suggests that the formulation can stimulate stem cells for the regeneration of dental tissue. Keywords: Stem cell, Dental caries, Sustained release, Aspirin, Dentinogenesis, Microsphere.

Nanofibers with genotyped Bacillus strains exhibiting antibacterial and immunomodulatory activity.

Biofilm-associated diseases such as periodontitis are widespread and challenging to treat which calls for new strategies for their effective management. Probiotics represent a promising approach for targeted treatment of dysbiosis in biofilm and modulation of host immune response. In this interdisciplinary study, nanofibers with two autochthonous Bacillus strains 27.3.Z and 25.2.M were developed. The strains were isolated from the oral microbiota of healthy individuals, and their genomes were sequenced and screened for genes associated with antimicrobial and immunomodulatory activities, virulence factors, and transferability of resistance to antibiotics. Spores of two Bacillus strains were incorporated individually or in combination into hydrophilic poly(ethylene oxide) (PEO) and composite PEO/alginate nanofibers. The nanofiber mats were characterised by a high loading of viable spores (> 7 log CFU/mg) and they maintained viability during electrospinning and 6months of storage at room temperature. Spores were rapidly released from PEO nanofibers, while presence of alginate in the nanofibers prolonged their release. All formulations exhibited swelling, followed by transformation of the nanofiber mat into a hydrogel and polymer erosion mediating spore release kinetics. The investigated Bacillus strains released metabolites, which were not cytotoxic to peripheral blood mononuclear cells (PBMCs) in vitro. Moreover, their metabolites exhibited antibacterial activity against two periodontopathogens, an antiproliferative effect on PBMCs, and inhibition of PBMC expression of proinflammatory cytokines. In summary, the developed nanofiber-based delivery system represents a promising therapeutic approach to combat biofilm-associated disease on two fronts, namely via modulation of the local microbiota with probiotic bacteria and host immune response with their metabolites.

Mefenamic acid modified-release by encapsulation in a k-carrageenan/sericin blend

Multiple dosages of mefenamic acid have been reported to result in side effects such as gastrointestinal discomfort, headaches and fatigue. Therefore, a modified release system for this drug could improve patient well-being and treatment adhesion. In this study, we developed a carrier based on k-carrageenan and sericin biomacromolecules. The produced particles presented great encapsulation rates, above 86.19 % and drug loading above 48.85 % In addition, the beads had a reproducible spherical shape and size ranging from 1.28 to 1.46 mm. The presence of the Active Pharmaceutical Ingredient (API) and its compatibility with the matrix were verified by XRD, SEM and FTIR. The in vitro release in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 9.0) without enzymes were less than 10 % and up to 100 %, respectively, which suggests gastroresistance. The release kinetics followed the Weibull model (R2adj 0.787–0.9922 and AIC 65.9798–36.7948) and indicated a release mechanism based on matrix swelling, polymer chain relaxation and erosion. Cell viability assay in the intestinal cell model Caco-2 showed that the blend and placebo were not cytotoxic (cell viability > 84 %), therefore suggesting citocompability. demonstrating that the carrier is biocompatible. Our results suggest that the proposed polymer matrix is capable of a high mefenamic acid loading, with in vitro indication of a sustained release of mefenamic acid for intestinal delivery, compatible with the gastrointestinal tissue.

Transport properties of hydrophilic compounds in PLGA microspheres

Biodegradable polyesters, such as the poly(lactic-co-glycolic acid) (PLGA), have been extensively used as a polymer matrix for entrapping a variety of active compounds. In this study, the physicochemical phenomena that control the mass transport mechanism of hydrophilic compounds released from PLGA microspheres were identified. This study aims to produce and characterize PLGA microspheres loaded with metformin hydrochloride (MH) and perform a case study using the literature data of PLGA microspheres loaded with fluorescein isothiocyanate-dextran (FITC-dextran). The MH is a low molecular weight compound that was easily and rapidly transported by diffusion mechanism through the microsphere pores. The FITC-dextran, as a high molecular weight compound, depended on the mechanism of polymer erosion and mesopore formation, with 18 days of duration, before its release by diffusion mass transfer. Values of the effective diffusion coefficient of MH and FITC-dextran, both in PLGA, were 2.4 x 10-13 and 5.3 x 10-18 m2 s-1, respectively, with a difference of five orders of magnitude attributed to the molecular weight of these hydrophilic compounds and the main mass transport that governed their release. This study provides important insights into the mechanisms of mass transfer and their correlation with the physicochemical properties of both hydrophilic compounds and the PLGA matrix, contributing to the development of biodegradable controlled delivery systems for a variety of applications in chemical, biotechnological, and pharmaceutical industries.

Polycaprolactone/epoxide-functionalized silica composite microparticles for long-term controlled release of trans-chalcone

Abstract In this study, controlled release of trans-chalcone was achieved by using a polycaprolactone-based hybrid system as the drug carrier material. Encapsulation efficiency was obtained in the range of 70–75% for various formulations and in vitro release studies, conducted at 37 °C and pH 7.4, revealed slow profile reaching 60% cumulative release. As interpreted from kinetic modelling, drug release was controlled mainly by Fickian diffusion; polymer erosion did not contribute to the TC release. Difference in drug loading efficiencies of the hybrid and neat PCL microparticles was observed such that PCL microparticles had lower loading efficiency than the hybrid microparticles whereas the release profiles were similar. pH of the release medium had affected release profiles; acidic medium enhanced drug release. Characterization of the microparticles were realized by FT-IR, TGA, DSC, SEM and WCA which revealed key properties such as molecular dispersion state and hydrophilicity. With the results obtained, we concluded that our hybrid system has a significant potential for long term release of trans-chalcone.

Polyanhydride Chemistry.

Polyanhydrides (PAs) are a class of synthetic biodegradable polymers employed as controlled drug delivery vehicles. They can be synthesized and scaled up from low-cost starting materials. The structure of PAs can be manipulated synthetically to meet desirable characteristics. PAs are biocompatible, biodegradable, and generate nontoxic metabolites upon degradation, which are easily eliminated from the body. The rate of water penetrating into the polyanhydride (PA) matrix is slower than the anhydride bond cleavage. This phenomenon sets PAs as "surface-eroding drug delivery carriers." Consequently, a variety of PA-based drug delivery carriers in the form of solid implants, pasty injectable formulations, microspheres, nanoparticles, etc. have been developed for the sustained release of small molecule drugs, and vaccines, peptide drugs, and nucleic acid-based active agents. The rate of drug delivery is often controlled by the polymer erosion rate, which is influenced by the polymer structure and composition, crystallinity, hydrophobicity, pH of the release medium, device size, configuration, etc. Owing to the above-mentioned interesting physicochemical and mechanical properties of PAs, the present review focuses on the advancements made in the domain of synthetic biodegradable biomedical PAs for therapeutic delivery applications. Various classes of PAs, their structures, their unique characteristics, their physicochemical and mechanical properties, and factors influencing surface erosion are discussed in detail. The review also summarizes various methods involved in the synthesis of PAs and their utility in the biomedical domain as drug, vaccine, and peptide delivery carriers in different formulations are reviewed.

Electrospun nanofibers for drug delivery applications: Methods and mechanism

AbstractElectrospinning procedures such as blend electrospinning, coaxial electrospinning, and emulsion electrospinning have been used for the fabrication of electrospun nanofibers (ENFs) for biomedical applications. These ENFs are attracted great interest especially in drug delivery applications due to their small size, high surface area‐to‐volume, and porosity. The aim of this review is to focus on the controlled release mechanism among the different electrospinning methods, and the selectivity of hydrophilic, water‐soluble polymers as a carrier for drug. The mechanism for the drug delivery depends mainly on the method of drug loading, polymeric interactions, and the nature of polymer swelling, erosion, or degradation. This review compressed on the literature survey about the fabrication of nanofibers by different electrospinning methods, factors affecting the nanofiber morphologies, selectivity of polymeric blends for successful controlled release behavior, and the mechanism involved in the drug release steps.

Evaluation of Hydroxyethyl Cellulose Grades as the Main Matrix Former to Produce 3D-Printed Controlled-Release Dosage Forms.

Diclofenac sodium tablets were successfully prepared via hot-melt extrusion (HME) and fused deposition modeling (FDM), using different molecular-weight (Mw) grades of hydroxyethyl cellulose (HEC) as the main excipient. Hydroxypropyl cellulose (HPC) was added to facilitate HME and to produce drug-loaded, uniform filaments. The effect of the HEC grades (90–1000 kDa) on the processability of HME and FDM was assessed. Mechanical properties of the filaments were evaluated using the three-point bend (3PB) test. Breaking stress and distance were set in relation to the filament feedability to identify printer-specific thresholds that enable proper feeding. The study demonstrated that despite the HEC grade used, all formulations were at least printable. However, only the HEC L formulation was feedable, showing the highest breaking stress (29.40 ± 1.52 MPa) and distance (1.54 ± 0.08 mm). Tablet drug release showed that the release was Mw dependent up to a certain HEC Mw limit (720 kDa). Overall, the release was driven by anomalous transport due to drug diffusion and polymer erosion. The results indicate that despite being underused in FDM, HEC is a suitable main excipient for 3D-printed dosage forms. More research on underutilized polymers in FDM should be encouraged to increase the limited availability.

Poly(Lactic Acid) Block Copolymers with Poly(Hexylene Succinate) as Microparticles for Long-Acting Injectables of Risperidone Drug.

In the present work, Risperidone microparticles from poly(lactic acid)/poly(hexylene succinate) (PLA-b-PHSu) block copolymers in different ratios, 95/05, 90/10 and 80/20 w/w, were examined as long-acting injectable formulations. Nuclear magnetic resonance (NMR) was used to verify the successful synthesis of copolymers. Enzymatic hydrolysis showed an increase in weight loss as the content of PHSu increased, while the cytotoxicity studies confirmed the biocompatibility of the copolymers. The polyesters were further used to encapsulate Risperidone by spray drying. The drug-loaded microparticles were studied by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray diffraction (XRD). SEM microphotographs confirmed that spherically shaped microparticles were prepared with sizes about 5–12 μm, while XRD and differential scanning calorimetry (DSC) studies evidenced that Risperidone was encapsulated in amorphous form. The drug loading and the entrapment efficiency of Risperidone were studied as well as the in vitro release from the prepared microparticles. As the content of PHSu increased, a higher release of Risperidone was observed, with PLA-b-PHSu 80/20 w/w succeeding to release 100% of RIS within 12 days. According to theoretical modeling, the kinetics of RIS release from PLA-b-PHSu microparticles is complex, governed by both diffusion and polymer erosion.