Methacrylic Acid-ethyl Acrylate Copolymer Research Articles

PH-responsive CuS/DSF/EL/PVP nanoplatform alleviates inflammatory bowel disease in mice via regulating gut immunity and microbiota

The clinical treatment of inflammatory bowel disease (IBD) is challenging. We developed copper sulfate (CuS)/disulfiram (DSF)/methacrylic acid-ethyl acrylate copolymer (EL)/polyvinylpyrrolidone (PVP) nanoplatform (CuS/DSF/EL/PVP) and evaluated its efficiency for treating IBD. After oral administration, the pH-sensitive EL protected the CuS/DSF/EL/PVP against degradation by acidic gastric juices. Once the colon was reached, EL was dissolved, releasing DSF and Cu2+. Further, the main in vivo metabolite of DSF can bind to Cu2+ and form copper (II) N, N-diethyldithiocarbamate (CuET), which significantly alleviated acute colitis in mice. Notably, CuS/DSF/EL/PVP outperformed CuS/EL/PVP and DSF/EL/PVP nanoplatforms in reducing colonic pathology and improving the secretion of inflammation-related cytokines (such as IL-4 and IL-10) in the colonic mucosa. RNA-seq analysis revealed that the nanoplatform reduced colonic inflammation and promoted intestinal mucosal repair by upregulating C-type lectin receptor (CLR)-related genes and signaling pathways. Furthermore, CuS/DSF/EL/PVP showed potential for improving colitis Th1/Th17 cells through innate immunity stimulation, down-regulation of inflammatory cytokines, and upregulation of anti-inflammatory cytokines. Additionally, the intervention with CuS/DSF/EL/PVP led to increased intestinal flora diversity, decreased Escherichia–Shigella abundance, and elevated levels of short-chain fatty acid (SCFA)-producing bacteria Prevotella, Lactobacillus, and Bifidobacterium, indicating their potential to modulate the dysregulated intestinal flora and suppress inflammation. Statement of SignificanceOur study introduces the CuS/DSF/EL/PVP nanoplatform as a therapeutic strategy for treating inflammatory bowel disease (IBD). This approach demonstrates significant efficacy in targeting the colon and alleviating acute colitis in mice. It uniquely modulates gut immunity and microbiota, exhibiting a notable impact on inflammation-related cytokines and promoting intestinal mucosal repair. The nanoplatform's ability to regulate gut flora diversity, combined with its cost-effective and scalable production, positions it as a potentially transformative treatment for IBD, offering new avenues for personalized medical interventions.

Processability evaluation of multiparticulate units prepared by selective laser sintering using the SeDeM Expert System approach

3D printing in dosage forms fabrication is in the focus of researchers, however, the attempts in multiparticulate units (MPUs) preparation are scarce. The aim of this study was to fabricate different size MPUs by selective laser sintering (SLS), using different polymers, and investigate their processability based on the SeDeM Expert System approach.MPUs (1- or 2-mm size) were prepared with model drug (ibuprofen or caffeine), polymer (poly(ethylene)oxide (PEO), ethyl cellulose (EC) or methacrylic acid-ethyl acrylate copolymer (MA-EA)) and printing aid. Comprehensive sample characterization was performed and experimentally obtained parameters were mathematically transformed and evaluated using the SeDeM Expert System framework. The obtained samples exhibited irregular shape, despite the spherical printing object design. Polymer incorporated notably affected MPUs properties.The obtained samples exhibited low bulk density, good flowability-, as well as stability-related parameters, which indicated their suitability for filling into capsules or sachets. Low density values implied that compressibility enhancing excipients may be required for MPUs incorporation in tablets. Samples containing EC and MA-EA were found suitable for compression, due to high compacts tensile strength. The obtained results indicate that SeDeM Expert System may extended from powder compressibility evaluation tool to framework facilitating powders/multiparticulate units processing.

ASD Formation Prior to Material Characterization as Key Parameter for Accurate Measurements and Subsequent Process Simulation for Hot-Melt Extrusion

Process simulation facilitates scale-up of hot-melt extrusion (HME) and enhances proper understanding of the underlying critical process parameters. However, performing numeric simulations requires profound knowledge of the employed materials’ properties. For example, an accurate description of the compounds’ melt rheology is paramount for proper simulations. Hence, sample preparation needs to be optimized to yield results as predictive as possible. To identify the optimal preparation method for small amplitude oscillatory shear (SAOS) rheological measurements, binary mixtures of hydroxypropylmethylcellulose acetate succinate or methacrylic acid ethyl acrylate copolymer (Eudragit L100-55) together with the model drugs celecoxib and ketoconazole were prepared. The physical powder mixtures were introduced into the SAOS as a compressed tablet or a disk prepared via vacuum compression molding (VCM). Simulations with the derived parameters were conducted and compared to lab-scale extrusion trials. VCM was identified as the ideal preparation method resulting in the highest similarity between simulated and experimental values, while simulation based on conventional powder-based methods insufficiently described the HME process.

Trojan pH-Sensitive Polymer Particles Produced in a Continuous-Flow Capillary Microfluidic Device Using Water-in-Oil-in-Water Double-Emulsion Droplets.

A facile and robust microfluidic method to produce nanoparticle-in-microparticle systems (Trojan systems) is reported as a delivery vector for the oral administration of active pharmaceutical ingredients. The microfluidic system is based on two coaxial capillaries that produce monodisperse water-in-oil-in-water (W/O/W) double emulsions in a highly controlled fashion with precise control over the resulting particle structure, including the core and shell dimensions. The influence of the three phase flow rates, pH and drying process on the formation and overall size is evaluated. These droplets are then used as templates for the production of pH-sensitive Trojan microparticles after solvent evaporation. The shell of Trojan microparticles is made of Eudragit®, a methacrylic acid-ethyl acrylate copolymer that would enable the Trojan microparticle payload to first pass through the stomach without being degraded and then dissolve in the intestinal fluid, releasing the inner payload. The synthesis of the pH-sensitive Trojan microparticles was also compared with a conventional batch production method. The payloads considered in this work were different in nature: (1) fluorescein, to validate the feasibility of the polymeric shell to protect the payload under gastric pH; (2) poly(D,L-lactic acid/glycolic acid)-PLGA nanoparticles loaded with the antibiotic rifampicin. These PLGA nanoparticles were produced also using a microfluidic continuous process and (3) PLGA nanoparticles loaded with Au nanoparticles to trace the PLGA formulation under different environments (gastric and intestinal), and to assess whether active pharmaceutical ingredient (API) encapsulation in PLGA is due efficiently. We further showed that Trojan microparticles released the embedded PLGA nanoparticles in contact with suitable media, as confirmed by electron microscopy. Finally, the results show the possibility of developing Trojan microparticles in a continuous manner with the ability to deliver therapeutic nanoparticles in the gastrointestinal tract.

Boost of solubility and supersaturation of celecoxib via synergistic interactions of methacrylic acid-ethyl acrylate copolymer (1:1) and hydroxypropyl cellulose in ternary amorphous solid dispersions

A current trend in the development of amorphous solid dispersions (ASDs) is the combination of two polymers for synergistic enhancement in supersaturation of poorly soluble drugs. We investigated the supersaturation potential of celecoxib (CXB) using combinations of methacrylic acid-ethyl acrylate copolymer (1:1) (EL 100–55) and hydroxypropyl cellulose (HPC) SSL. Initially, the supersaturation potential of single polymers and combinations in various ratios was assessed. While EL 100–55 and HPC SSL alone showed limited potential in solubility enhancement of CXB the combination of both polymers led to a boost of CXB solubility, whereby most promising results were obtained using a 50:50 polymer ratio. Binary and ternary CXB ASDs (10% drug load) were prepared via vacuum compressing molding (VCM) and hot melt extrusion (HME). ASDs were studied by exploring the miscibility and intermolecular interactions and tested for their dissolution performance. HPC SSL was identified to be a suitable precipitation inhibitor when added to a fast dissolving CXB: EL 100–55 ASD. Ternary ASDs showed even further dissolution improvement, when processed by HME. The combination of heat and shear stress led to a homogeneous and intimate mixture of EL 100–55 and HPC SSL, resulting in formation of synergistic interactions with pronounced impact on CXB supersaturation.

Development, Characterization, Optimization, and In Vivo Evaluation of Methacrylic Acid-Ethyl Acrylate Copolymer Nanoparticles Loaded with Glibenclamide in Diabetic Rats for Oral Administration.

The methacrylic acid–ethyl acrylate copolymer nanoparticles were prepared using the solvent displacement method. The independent variables were the drug/polymer ratio, surfactant concentration, Polioxyl 40 hydrogenated castor oil, the added water volume, time, and stirring speed, while size, PDI, zeta potential, and encapsulation efficiency were the response variables analyzed. A design of screening experiments was carried out to subsequently perform the optimization of the nanoparticle preparation process. The optimal formulation was characterized through the dependent variables size, PDI, zeta potential, encapsulation efficiency and drug release profiles. In vivo tests were performed in Wistar rats previously induced with diabetes by administration of streptozotocin. Once hyperglycemia was determined in rats, a suspension of nanoparticles loaded with glibenclamide was administered to them while the other group was administered with tablets of glibenclamide. The optimal nanoparticle formulation obtained a size of 18.98 +/− 9.14 nm with a PDI of 0.37085 +/− 0.014 and a zeta potential of −13.7125 +/− 1.82 mV; the encapsulation efficiency was of 44.5%. The in vivo model demonstrated a significant effect (p < 0.05) between the group administered with nanoparticles loaded with glibenclamide and the group administered with tablets compared to the group of untreated individuals.

Polymerization Mechanism and Kinetics of Preparation of Methacrylic Acid-Ethyl Acrylate Copolymer Emulsion Reverse Demulsifier

It was shown that methacrylic acid-ethyl acrylate copolymer (P(EA-MAA)) emulsion has a good reverse demulsification performance for treatment of water produced in oilfields. Its polymerization mechanism, kinetics and demulsification mechanism are important for its application and scale-up production. Therefore, they were studied in the research described in this paper. It was found that the demulsification mechanism of P(EA-MAA) was related to the ion compositions of the produced water and the conformation change of P(EA-MAA) when it was dissolved in the produced water. The distributions of monomer and surfactant before the polymerization were investigated and we found that there were both homogeneous nucleation and micellar nucleation during the first stage of emulsion polymerization. The relationships among the polymerization rate (Rp), monomer concentration ([M]), initiator concentration ([I]) and surfactant concentration ([S]) were studied. The emulsion copolymerization kinetic equation was Rp∝[M]0.64 [I]0.68 [S]0.41, which is related with the nucleation mechanism of the polymerization mechanism. In addition, the activation energy was 34.50 kJ/mol.

Influence of Particle Size and Drug Load on Amorphous Solid Dispersions Containing pH-Dependent Soluble Polymers and the Weak Base Ketoconazole

Among the great number of poorly soluble drugs in pharmaceutical development, most of them are weak bases. Typically, they readily dissolve in an acidic environment but are prone to precipitation at elevated pH. This was aimed to be counteracted by the preparation of amorphous solid dispersions (ASDs) using the pH-dependent soluble polymers methacrylic acid ethylacrylate copolymer (Eudragit L100–55) and hydroxypropylmethylcellulose acetate succinate (HPMCAS) via hot-melt extrusion. The hot-melt extruded ASDs were of amorphous nature and single phased with the presence of specific interactions between drug and polymer as revealed by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR). The ASDs were milled and classified into six particle size fractions. We investigated the influence of particle size, drug load, and polymer type on the dissolution performance. The best dissolution performance was achieved for the ASD made from Eudragit L100–55 at a drug load of 10%, whereby the dissolution rate was inversely proportional to the particle size. Within a pH-shift dissolution experiment (from pH 1 to pH 6.8), amorphous-amorphous phase separation occurred as a result of exposure to acidic medium which caused markedly reduced dissolution rates at subsequent higher pH values. Phase separation could be prevented by using enteric capsules (Vcaps Enteric®), which provided optimal dissolution profiles for the Eudragit L100–55 ASD at a drug load of 10%.

Impact of Hot-Melt Extrusion Processing Conditions on Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer

For successful formulation of amorphous solid dispersions (ASDs) using hot-melt extrusion, it is imperative to understand the effect that heat and shear rate has on the physicochemical properties of the excipient. In this study, we investigated the influence of hot-melt extrusion parameters on solvent-free binary ASDs of ibuprofen (IBU), a model active pharmaceutical ingredient, in methacrylic acid-ethyl acrylate copolymer type A, 1:1, EUDRAGIT® L100-55 (EUD). To evaluate the impact of barrel temperature, screw speed, and residence time on EUD mass average molar mass and IBU release profile, size-exclusion chromatography and dissolution testing were used, respectively. The optimal conditions were established for IBU loadings less than 40 wt. %. For ASD formulations prepared using the ideal variables, spectral and thermal analyses confirmed that, under dry conditions at a temperature of 25°C, IBU remained amorphous during an 18-month storage period. After 28 months, formulations with active pharmaceutical ingredient content above 30 wt. % started to recrystallize. A temperature–composition phase diagram, constructed using melting point depression and glass-transition temperature measurements of IBU–EUD mixtures, correlated well with the long-term physical stability. The effect that minor-to-moderate polymer degradation within the extrudates has on their long-term physical stability and dissolution characteristics is analyzed and discussed.

Amorphous solid dispersions of weak bases with pH-dependent soluble polymers to overcome limited bioavailability due to gastric pH variability – An in-vitro approach

Several drugs are pH-dependent soluble weak bases with a poor solubility in the intestinal pH range. Additionally a variable gastric pH, which is a common issue in the population, potentially reduces the in-vivo performance due to reduced solubility at elevated pH. Aiming to avoid the influence of variable gastric pH on the dissolution performance, enteric polymers – hydroxypropylmethylcellulose acetate succinate (HPMCAS), hydroxypropylmethylcellulose phthalate (HP-55, HP-50) and methacrylic acid ethylacrylate copolymer (Eudragit L100-55) together with nevirapine as model drug were used for the preparation of solid dispersions by hot-melt extrusion. We were able to generate solid dispersions without crystalline residuals. The resulting solid dispersions were further tested for stability and dissolution performance applying two different pH-shift experiments (non-sink conditions), to simulate standard and altered gastric conditions. Solid dispersions made of enteric polymers were independent to gastric pH variability and exhibited superior dissolution performances compared to their respective physical mixtures and neat nevirapine.

The influence of polymer excipients on the dissolution and recrystallization behavior of ketoconazole: Application, variation and practical aspects of a pH shift method

The formulation of amorphous solid dispersions (ASDs) is an effective way to improve the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). The combination of an amorphous state of the drug and the presence of crystallization-inhibiting polymers retains a high amount of dissolved API over time. ASDs with ketoconazole and different polymers were manufactured by spray drying and their characteristics as well as performance were analyzed. Dissolution tests with a change of the dissolution medium from 0.1 M HCl to phosphate buffer at pH 6.8 to simulate pH conditions for instant release formulations, and a direct dissolution of the ASDs in phosphate buffer pH 6.8 to simulate conditions for an enteric formulation, were performed. All ASDs with API contents between 25 and 50% by weight were completely X-ray amorphous. Varying dissolution behaviors between medium change and direct dissolution occurred. It was possible to identify the superior ASD-compositions for both types of tests. The acidic polymers methacrylic acid-ethyl acrylate copolymer, hypromellose acetate succinate and the solubilizer macrogolglycerol hydroxystearate showed the best performances. The combination of the acidic polymers with macrogolglycerol hydroxystearate showed an improved dissolution behavior at higher API contents. The optimization of such formulations with different release-patterns plays an important role for the enhancement of the oral bioavailability of poorly water-soluble drugs.

Structural and optical properties of VO2+doped methacrylic acid ethylacrylate (MAA:EA) copolymer films

AbstractPure and VO2+doped methacrylic acid ethylacrylate (MAA:EA) copolymer films were prepared by using a solution casting method. Various techniques including X-ray diffraction, Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, scanning electron microscopy and electron paramagnetic resonance were employed for characterization of the samples. XRD patterns showed some degree of crystallinity of the doped polymer films due to interaction of the MAA:EA copolymer with VO2+. FT-IR spectral studies of pure and VO2+doped MAA:EA copolymer films displayed significant structural changes within the doped copolymer film indicating the complexation. The optical absorbance of the pure and VO2+doped films were measured in the 200 nm to 800 nm wavelength range. The values of the absorption edge and indirect band gaps were calculated. The optical band gap decreased with the increase of mol% of VO2+. From the EPR spectra, the spin- Hamiltonian parameters (g and A) were evaluated. The values of the spin-Hamiltonian parameters confirmed that the vanadyl ions were present in MAA:EA copolymer films as VO2+molecular ions in an octahedral site with a tetragonal compression (C4v). The morphology of the copolymer samples was examined by scanning electron microscopy. The enhanced crystalline nature of the doped copolymer was identified from SEM analysis.

Structural, Thermal and Optical Properties of Mn2+ Doped Methacrylic Acid – Ethyl Acrylate (MAA:EA) Copolymer Films

Abstract Pure and Mn2+ doped Methacrylic Acid Ethylacrylate (MAA:EA) copolymer films were prepared by using the solution cast technique. Investigations were conducted using DSC, TGA, XRD, FTIR, UV–Vis, SEM and EPR. Thermal properties of these films were investigated with differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Using the DSC thermograms, glass transition temperature (Tg ) and melting temperature (Tm ) of copolymer films were measured. Thermogravimetric curves of the pure and Mn2+ doped MAA:EA copolymer showed two distinct steps of weight loss. The optical absorbance of the pure and Mn2+ doped films were measured in the 200–800 nm wavelength range. The values of absorption edge, direct and indirect band gaps were calculated. The optical band gap decreased with the increase of mol% of Mn2+ ions. The enhanced amorphous nature of the doped copolymer has been identified from X-ray diffraction analysis. FTIR spectral studies of pure and Mn2+ doped MAA:EA copolymer films display significant structural changes within the copolymer film indicating the complexation. The morphology of the copolymer samples was examined by scanning electron microscopy (SEM). EPR spectra of all the doped samples exhibit a single absorption line centered at g=2.005. The observed variation in the EPR signal intensity is due to the existence of interacting paramagnetic centers.

Characterization of Variant Soft Nanoparticle Structure and Morphology in Solution by NMR Spectroscopy

The physicochemical properties of soft nanoparticles, most notably size, morphology, and ligand interactions, typically depend upon the solution environment in which they are suspended. Comprehensive characterization in a given environment is therefore essential. We have employed high-resolution solution nuclear magnetic resonance (NMR) spectroscopy, nuclear spin relaxation measurements, and diffusion ordered NMR spectroscopy (DOSY) techniques to thoroughly characterize polymeric nanoparticles formed by salt-induced collapse of a methacrylic acid–ethyl acrylate copolymer stabilized by ultraviolet (UV) irradiation. UV-dose-dependent production of new chemical species is apparent from 1H and 13C chemical shift patterns. 1H–13C correlation spectroscopy reveals that cross-linking is likely responsible for nanoparticle structural integrity. Paramagnetic relaxation enhancement (PRE) unambiguously shows protection of photochemically derived moieties from solvent, with a UV-dose-dependent decrease in particle siz...

In vitro dissolution of proton-pump inhibitor products intended for paediatric and geriatric use in physiological bicarbonate buffer

Proton-pump inhibitor (PPI) products based on enteric coated multiparticulates are design to meet the needs of patients who cannot swallow tablets such as children and older adults. Enteric coated PPI preparations exhibit delays in in vivo absorption and onset of antisecretory effects, which is not reflected by the rapid in vitro dissolution in compendial pH 6.8 phosphate buffer commonly used for assessment of these products. A more representative and physiological medium, pH 6.8 mHanks bicarbonate buffer, was used in this study to evaluate the in vitro dissolution of enteric coated multiparticulate-based PPI products. Commercially available omeprazole, lansoprazole and esomeprazole products were subject to dissolution tests using USP-II apparatus in pH 4.5 phosphate buffer saline for 45min (acid stage) followed by pH 6.8 phosphate buffer or pH 6.8 mHanks bicarbonate buffer. In pH 6.8 phosphate buffer, all nine tested products displayed rapid and comparable dissolution profiles meeting the pharmacopeia requirements for delayed release preparations. In pH 6.8 mHanks buffer, drug release was delayed and failed the pharmacopeia requirements from most enteric coated preparations. Despite that the same enteric polymer, methacrylic acid–ethyl acrylate copolymer (1:1), was applied to all commercial multiparticulate-based products, marked differences were observed between dissolution profiles of these preparations. The use of pH 6.8 physiological bicarbonate (mHanks) buffer can serve as a useful tool to provide realistic and discriminative in vitro release assessment of enteric coated PPI preparations and to assist rational formulation development of these products.

Coatings from blends of Eudragit® RL and L55: A novel approach in pH-controlled drug release

The aim of the present study was to investigate the drug release from theophylline pellets coated with blends of quaternary polymethacrylate and methacrylic acid–ethyl acrylate copolymers. Pellets were coated with blends of Eudragit® RL PO (RL) and Eudragit® L 100-55 (L55) in either organic solution or aqueous dispersion at various copolymer ratios. Generally, the coatings were less permeable for theophylline in phosphate buffer pH 6.8 than they were in hydrochloric acid pH 1.2. Further dissolution experiments revealed that the differences in drug release are caused by the different pH values. A design of experiments for historical data was performed on drug release data of pellets with different coating levels and blend ratios of RL and L55. Drug release in hydrochloric acid was predominantly affected by the coating level, whereas for drug release in phosphate buffer pH 6.8 the blend ratio was the determining factor. As expected, dissolution experiments at different pH values showed that drug release depends on the ratio of dissociated L55 to RL because ionization is a requirement for the functional groups to interact. With the dissolution test for delayed-release solid dosage forms (Ph. Eur.) it was demonstrated that the unique release behavior in neutral media is preserved after the exposition to hydrochloric acid. These findings indicate that the combination of RL and L55 in coatings prepared from solutions is a promising approach for controlled drug release.

Calculation of reactivity ratios of methacrylic acid-ethyl acrylate copolymer by on-line quantitative 1H NMR spectroscopy

The solution copolymerization of methacrylic acid (MAA) and ethyl acrylate (EA) was studied by online proton nuclear magnetic resonance spectroscopy (1H NMR) using 2,2′–azobisisobutyronitrile as an initiator in deuterated dimethyl sulfoxide at 60 °C. The chemical compositions of the copolymer and the comonomer concentrations were determined from the conversion of comonomers to copolymer by quantitative in situ NMR monitoring to estimate the reactivity ratios of the comonomers at low conversion. This is a new and easy methodology to analyze radical copolymerization. In this research, it is shown that monomer reactivity ratios can be calculated by data collected only from one initial comonomer mixture composition via online monitoring progress of the copolymerization reaction. The reactivity ratios of MAA and EA are equal to 2.360 and 0.414, respectively. This approach is used to compute the monomer reactivity ratios in a nonlinear integrated form of the copolymerization equation which is described by Mayo and Lewis terminal model. The fairly good agreement between the results and the literature data reported for the emulsion system represent the accuracy of the reactivity ratios calculated by this new approach. The calculated reactivity ratios for emulsion copolymerization are rMAA = 2.040 and rEA = 0.470, and the previous literature data are rMAA = 2.580 and rEA = 0.157.

Strain Screening, Fermentation, Separation, and Encapsulation for Production of Nattokinase Functional Food

This study presents a novel and integrated preparation technology for nattokinase functional food, including strain screening, fermentation, separation, and encapsulation. To rapidly screen a nattokinase-productive strain, PCR-based screening method was combined with fibrinolytic activity-based method, and a high productive strain, Bacillus subtilis LSSE-22, was isolated from Chinese soybean paste. Reduction of poly-γ-glutamic acid (γ-PGA) concentration may contribute to separation of nattokinase and reduction of late-onset anaphylaxis risk. Chickpeas were confirmed as the favorable substrate for enhancement of nattokinase production and reduction of γ-PGA yield. Using cracked chickpeas, the nattokinase activity reached 356.25 ± 17.18 FU/g (dry weight), which is much higher than previous reports. To further reduce γ-PGA concentration, ethanol fractional extraction and precipitation were applied for separation of nattokinase. By extraction with 50 % and precipitation with 75 % ethanol solution, 4,000.58 ± 192.98 FU/g of nattokinase powders were obtained, and the activity recovery reached 89 ± 1 %, while γ-PGA recovery was reduced to 21 ± 2 %. To improve the nattokinase stability at acidic pH condition, the nattokinase powders were encapsulated, and then coated with methacrylic acid-ethyl acrylate copolymer. After encapsulation, the nattokinase was protected from being denatured under various acid conditions, and pH-responsible controlled release at simulated intestinal fluid was realized.

Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers

Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid–ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids.

Electron microscope characterization of drug release from methacrylic acid-ethyl acrylate copolymer-coated cross-linked alginate-gelatine beads

Drug release from alginate-based beads is generally a fast process influenced by parameters such as bead production technique and drug physicochemical properties. In a previous report new cross-linked alginate-gelatin beads were developed, with the ability to successfully prolong drug release. The present work is focused on scanning electron microscopy analysis of the morphological modifications of cross-linked alginate-gelatin beads occurring throughout enteric coating with a methacrylic acid-ethyl acrylate copolymer and in vitro release studies. The coating material remains unchanged in gastric pH conditions irrespective either of the irregular thickness of the coating layer or related changes observed in the inner matrix. In phosphate buffer pH 7.4 the coating dissolves immediately and the cross-linked matrix tends to swell influencing drug release. However, beads maintained their shape throughout the dissolution test, presenting a prolonged drug release profile. The cross-linking bonds contribute to the particle keeping its shape throughout release. Microscopical analysis confirms that matrix modification by the cross-linking reaction is crucial for the controlled release of the model drug (pindolol) from alginate beads.