Eudragit Research Articles

Toxicological analysis of chronic exposure to polymeric nanocapsules with different coatings in Drosophila melanogaster

Nanotechnology involves the utilization of nanomaterials, including polymeric nanocapsules (NCs) that are drug carriers. For modify drug release and stability, nanoformulations can feature different types of polymers as surface coatings: Polysorbate 80 (P80), Polyethylene glycol (PEG), Chitosan (CS) and Eudragit (EUD). Although nanoencapsulation aims to reduce side effects, these polymers can interact with living organisms, inducing events in the antioxidant system. Thus far, little has been described about the impacts of chronic exposure, with Drosophila melanogaster being an in vivo model for characterizing the toxicology of these polymers. This study analyzes the effects of chronic exposure to polymeric NCs with different coatings. Flies were exposed to 10, 50, 100, and 500 μL of NCP80, NCPEG, NCCS, or EUD. The survival rate, locomotor changes, oxidative stress markers, cell viability, and Nrf2 expression were evaluated. Between the coatings, NCPEG had minimal effects, as only 500 μL affected the levels of reactive species (RS) and the enzymatic activities of catalase (CAT) and glutathione S-transferase (GST) without reducing Nrf2 expression. However, NCEUD significantly impacted the total flies killed, RS, CAT, and Superoxide dismutase from 100 μL. In part, the toxicity mechanisms of these coatings can be explained by the imbalance of the antioxidant system. This research provided initial evidence on the chronic toxicology of these nanomaterials in D. melanogaster to clarify the nanosafety profile of these polymers in future nanoformulations. Further investigations are essential to characterize possible biochemical pathways involved in the toxicity of these polymeric coatings.

Electrospun EU/HPMC nanofibers decorated by ZIF-8 nanoparticle as the advanced electrochemical biosensor modifier for sensitive and selective detection of c-MET cancer biomarker in human plasma sample

This research presents a selective and sensitive electrochemical biosensor for the detection of the mesenchymal–epithelial transition factor (c-MET). The biosensing is based on a modification of the SPCE (screen-printed carbon electrode) with the electrospun nanofiber containing eudragit (EU), hydroxypropyl methylcellulose (HPMC), and Zeolite imidazolate frameworks (ZIF-8) nanoparticles. EU/HPMC/ZIF-8 nanofibers have presented a high capability of electron transfer, and more active surface area than bare SPCE due to synergistic effects between EU, HPMC, and ZIF-8. On the other hand, EU/HPMC nanofibers provided high porosity, flexible structures, high specific surface area, and good mechanical strength. The presence of ZIF-8 nanoparticles improved the immobilization of anti-c-MET on the modified SPCE and also resulted in increasing the conductivity. By c-MET incubation on the modified SPCE, c-MET was connected to anti-c-MET, and consequently the electrochemical signal of [Fe(CN)6]3-/4- as the anion redox probe was reduced. In order to investigate the structural and morphological characteristics and elemental composition of electrospun nanofibers, various characterization methods including FE-SEM, XRD, FTIR, and EDS were used. Under optimum conditions with a working potential range −0.3−0.6 V (vs. Ag/AgCl), linear range (LR), correlation coefficient (R2), sensitivity, and limit of detection (LOD) were acquired at 100 fg/mL-100 ng/mL, 0.9985, 53.28 μA/cm2.dec, and 1.28 fg/mL, respectively. Moreover, the mentioned biosensor was investigated in a human plasma sample to determine c-MET and showed ideal results including reproducibility, stability, and good selectivity against other proteins.

Obliteration of H. pylori infection through the development of a novel thyme oil laden nanoporous gastric floating microsponge

Thyme oil (TO) is a valuable essential oil believed to possess a variety of bioactivities, including antibacterial, anticancer, and antioxidant properties. These attributes grant TO the excellent capability to treat a wide range of diseases, particularly the effective eradication of Helicobacter pylori infection in the stomach. However, its practical use is limited by its low stability under atmospheric conditions. Our current research aims to encapsulate TO in eudragit (EGT) microsponges to enhance its stability and improve its effectiveness against H. pylori. The TO microsponges were prepared using EGT as a polymer, polysorbate 80 as a stabilizer, and dichloromethane (DCM) as a solvent via the quasi-emulsion solvent evaporation method. The product yield, particle size, surface morphology, entrapment efficiency, drug-polymer interaction, in-vitro floating, and in-vitro drug release of the microsponges were evaluated. The most promising microsponge was tested against H. pylori ATCC 43504 strains. The results showed that the microsponges exhibited a high product yield (ranging from 41 % ± 0.75–81.27 % ± 1.13), excellent entrapment efficiency (ranging from 63.01 % ± 0.79–88.64 % ± 0.98), prolonged in-vitro floating time (more than 12 h) and sustained in-vitro drug release for 18 h (81.53 %). Scanning electron microscopy results indicated that the microsponges were spherical in shape with a spongy surface. The average particle size of the selected microsponges was determined to be 49.79 ± 1.4 μm, and their average pore size was measured to be 0.81 ± 0.14 μm. DSC study results revealed that TO was physically entrapped in the microsponges. In-vitro anti-H. pylori activity studies demonstrated that TO in microsponge was more effective against H. pylori than pure TO. In conclusion, the developed microsponges containing thyme oil provide a promising alternative for the efficient targeting and eradication of H. Pylori infection.

Micro-interaction of montmorillonite-loaded nanoparticles with mucin promotes retention of betaxolol hydrochloride on the ocular surface and the tear film microenvironment

This work developed a triple-encapsulated nano-delivery system for topical and long-term glaucoma treatment. We encapsulated betaxolol hydrochloride (BH), a glaucoma drug loaded in refined acid-treated montmorillonite (RAMt), in hyaluronic acid/chitosan (HA/CS) cross-linked nanoparticles with high encapsulation efficiency and further wrapped them with Eudragit (ED) films to achieve dual sustained release. RAMt-BH-HA/CS@ED NPs exhibited excellent physicochemical properties for the sustained release of betaxolol hydrochloride. In vitro release experiments were performed, and the results showed that the drug release lasted for up to 8 h. Then, particle surface hydrophobicity experiments showed that the nanoparticles had both hydrophilic and hydrophobic properties. The ocular safety of the nanoparticles was confirmed by the chick embryo allantoic membrane assay and the rabbit blink frequency test. In the mucin-nanoparticle interaction experiments, the interaction between the nanoparticles and the mucin solution with high pH and low concentration (simulating the aqueous layer microenvironment of tears) was stronger than that with low pH and high concentration (simulating the tear mucin layer microenvironment of tears). Therefore, the nanoparticles showed excellent retention properties in tears and cornea. In vivo experiments in a rabbit model of elevated intraocular pressure demonstrated that the IOP-lowering effect was sustained for more than 12 hours. In conclusion, nanoparticles effectively lower IOP with excellent tolerability, and offer promising applications for long-term treatment of glaucoma.

Effect and Mechanism of Pharmaceutical Excipients on Berberine to Alleviate Ulcerative Colitis via Regulating Gut Microbiota.

Background: Various potential effect of drugs on alleviating diseases by regulating intestinal microbiome as well as the pharmaceutical excipients on gut microbiota has been revealed. However, the interaction between them is rarely investigated. Methods: Histological analysis, immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) analysis, RT-qPCR, and 16S rRNA analysis were utilized to explore the effect mechanism of the five excipients including hydroxypropyl methylcellulose (HPMC) F4M, Eudragit (EU) S100, chitosan (CT), pectin (PT), and rheum officinale polysaccharide (DHP) on berberine (BBR) to cure UC. Results: The combined BBR with PT and DHP group exhibited better therapeutic efficacy of UC with significantly increased colon length, and decreased hematoxylin-eosin (H&E) scores than other groups. Furthermore, the expression of tight junction ZO-1 and occludin in colon tissue were upregulated, and claudin-2 was downregulated. Ultimately, the serum content of tumor necrosis (TNF)-α, interleukin (IL)-1β, and IL-6 was decreased. Moreover, the combined BBR with PT significantly promoted the restoration of gut microbiota. The relative abundance of Firmicutes and Lactobacillus was significantly increased by the supplement of PT and DHP, and the relative abundance of Proteobacteria was downregulated. Conclusions: Our study may provide a new perspective that the selection of pharmaceutical excipients could be a crucial factor affecting the drugs’ therapeutic efficiency outcome.

Ranitidine hydrochloride stomach specific bouyant microsponge: Preparation, in-vitro characterization, and in-vivo anti-ulcer activity

Ranitidine HCl (RTD) is the safest drug used to treat a life-threatening disease gastric ulcer. Therefore, sustained-release gastric buoyant microsponges of RTD were prepared by employing a double emulsion method. In the formulation of these microsponges eudragit (EGT) was a polymer, xanthan gum (XG) was used to impart non collapsible structure to microsponges, and tween 80 was used as an emulgent and all prepared microsponges were characterized for in-vitro studies and the best microsponge was evaluated for in-vivo antiulcer activity in albino rat model. All RTD microsponges exhibited appreciable in-vitro floating behavior and also showed initial burst release followed by sustained release of RTD in an acidic medium. However, microsponge formulation with RTD to EGT ratio (1:1) illustrated comparatively high in-vitro drug release (71.9% ± 2.79 in 12 h) and it also demonstrated appreciable production yield (81.3% ± 1.92), drug content (60.03% ± 1.81), and entrapment efficiency (68.2% ± 1.40). SEM study revealed the formation of RTD microsponge. Furthermore, In-vivo anti-ulcer activity study results showed that the studied microsponge exhibited more protective and healing effects in induced gastric ulcers in albino rats than pure RTD. Thus, it could be concluded that the gastric buoyant microsponge could be a useful approach to improve the anti-ulcer effect of RTD.

Wrinkling of an Enteric Coating Induced by Vapor-Deposited Stimuli-Responsive Hydrogel Thin Films.

In this contribution, we report on the thin-film synthesis of a thermoresponsive polymer onto another polymer used as an enteric coating in drug applications. In particular, we deposit cross-linked poly(N-vinylcaprolactam) (pNVCL) thin films by initiated chemical vapor deposition (iCVD) onto spin-coated Eudragit (EUD) layers. Already upon iCVD synthesis, the layered structure starts to form wrinkles at a minimum iCVD thickness of 30 nm. By changing the EUD layer thickness and the amount of cross-linking used during iCVD, the morphology of the wrinkles is demonstrated to be readily tunable. Laterally, the double-layer structures vary in morphology from being ultrasmooth to exhibiting up to a 3.5 μm wrinkle wavelength. The surface roughness and, thus, the wrinkles’ height can be tailored from below 1 nm up to 100 nm. From the resulting wavelength of wrinkles, an estimation of the elastic modulus of pNVCL proves its tunability over a wide range of values thanks to the iCVD process. This study elucidates an uncomplicated way to tune the wrinkles’ morphology and, thus, the surface area of a system that can be employed in drug delivery applications. Hence, an enteric coating of EUD together with an iCVD-synthesized thermoresponsive thin film is proposed as a promising composite encapsulation layer to outperform established systems in terms of tunability of the response to multiple external stimuli.

Novel nano-encapsulation of probucol in microgels: scanning electron micrograph characterizations, buoyancy profiling, and antioxidant assay analyses

Smart polymers such as Eudragit (ED) have shown potential applications in oral drug delivery and targeted release. Probucol (PB) is a lipophilic drug used for hypercholesterolemia and possesses desirable antidiabetic effects such as antioxidant and cell protective effects. PB is highly hydrophobic and has poor bioavailability with significant inter- and intra-patient absorption, limiting its clinical applications in diabetes. This study aimed to design and analyse new PB-ED formulations with or without the absorption-enhancer chenodeoxycholic acid (CDCA). Sodium alginate-based microcapsules containing three different ED polymers (NM30D, RL30D and RS30D) were investigated with or without CDCA via scanning electron microscopy, energy dispersive X-ray spectroscopy (EDXR), confocal microscopy, osmotic stability, mechanical properties, buoyancy, release profiles (pH: 7.4), thermal stability and antioxidant effects. The effects of microcapsules on pancreatic β-cell survival, function, inflammatory profile and PB cellular uptake were analysed. All microcapsules showed uniform morphology and surface topography with CDCA being distributed evenly throughout the microcapsules. Osmotic stability was significantly improved in PB-NM30D and PB-RL30D microcapsules (p < .01 and p < .05, respectively), and PB-NM30D microcapsules displayed low buoyancy (p < .01). CDCA improved PB-NM30D effects on pancreatic β-cell function and bioenergetics, which suggests potential application of PB-NM30D-CDCA in PB delivery and diabetes treatment.

Polymeric Precipitation Inhibitors Promote Fenofibrate Supersaturation and Enhance Drug Absorption from a Type IV Lipid-Based Formulation.

The ability of lipid-based formulations (LBFs) to increase the solubilization, and prolong the supersaturation, of poorly water-soluble drugs (PWSDs) in the gastrointestinal (GI) fluids has generated significant interest in the past decade. One mechanism to enhance the utility of LBFs is to prolong supersaturation via the addition of polymers that inhibit drug precipitation (polymeric precipitation inhibitors or PPIs) to the formulation. In this work, we have evaluated the performance of a range of PPIs and have identified PPIs that are sufficiently soluble in LBF to allow the construction of single phase formulations. An in vitro model was first employed to assess drug (fenofibrate) solubilization and supersaturation on LBF dispersion and digestion. An in vitro-in situ model was subsequently employed to simultaneously evaluate the impact of PPI enhanced drug supersaturation on drug absorption in rats. The stabilizing effect of the polymers was polymer specific and most pronounced at higher drug loads. Polymers that were soluble in LBF allowed simple processing as single phase formulations, while formulations containing more hydrophilic polymers required polymer suspension in the formulation. The lipid-soluble polymers Eudragit (EU) RL100 and poly(propylene glycol) bis(2-aminopropyl ether) (PPGAE) and the water-soluble polymer hydroxypropylmethyl cellulose (HPMC) E4M were identified as the most effective PPIs in delaying fenofibrate precipitation in vitro. An in vitro model of lipid digestion was subsequently coupled directly to an in situ single pass intestinal perfusion assay to evaluate the influence of PPIs on fenofibrate absorption from LBFs in vivo. This coupled model allowed for real-time evaluation of the impact of supersaturation stabilization on absorptive drug flux and provided better discrimination between the different PPIs and formulations. In the presence of the in situ absorption sink, increased fenofibrate supersaturation resulted in increased drug exposure, and a good correlation was found between the degree of in vitro supersaturation and in vivo drug exposure. An improved in vitro-in vivo correlation was apparent when comparing the same formulation under different supersaturation conditions. These observations directly exemplify the potential utility of PPIs in promoting drug absorption from LBF, via stabilization of supersaturation, and further confirm that relatively brief periods of supersaturation may be sufficient to promote drug absorption, at least for highly permeable drugs such as fenofibrate.

Dexibuprofen nanocrystals with improved therapeutic performance: fabrication, characterization, in silico modeling, and in vivo evaluation.

BackgroundThe aim of this study was to prepare and evaluate the impact of polymers on fabricating stable dexibuprofen (Dexi) nanocrystals with enhanced therapeutic potential, using a low energy, anti-solvent precipitation method coupled with molecular modelling approach.MethodsDexi nanocrystals were prepared using antisolvent precipitation with syringe pump. Crystallinity of the processed Dexi particles was confirmed using differential scanning calorimetry and powdered X-ray diffraction and transmission electron microscopy. Dissolution of Dexi nanocrystals was compared with raw Dexi and marketed tablets. Molecular modelling study was coupled with experimental studies to rationalise the appropriate polymers for stable Dexi nanocrystals. Antinociceptive study was carried out using balb mice.ResultsCombinations of hydroxypropyl methylcellulose (HPMC)–polyvinyl pyrrolidone (PVP) and HPMC–Eudragit (EUD) were shown to be very effective in producing stable Dexi nanocrystals with particle sizes of 85.0±2.5 nm and 90±3.0 nm, and polydispersity of 0.179±0.01, 0.182±0.02, respectively. The stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C–8°C and 25°C were more stable than those at 40°C. The maximum recovery of Dexi nanocrystals was observed from the formulations using the combination of HPMC–PVP and HPMC–EUD, which equated to 98% and 94% of the nominal active drug content respectively. The saturation solubility of the Dexi nanocrystals was substantially increased to 270.0±3.5 μg/mL compared to the raw Dexi in water (51.0±2.0 μg/mL) and stabilizer solution (92.0±3.0 μg/mL). Enhanced dissolution rate (P<0.05) was observed for the Dexi nanocrystals compared to the unprocessed drug substance and marketed tablets. Dexi nanocrystals produced the analgesic effect at much lower doses (5 mg/kg) than that of control standard, diclofenac sodium (20 mg/kg) and Dexi counterparts (40 mg/kg).ConclusionHPMC-PVP and HPMC-EUD were found the best polymer combination to stabilise Dexi nanocrystals. The Dexi nanocrystals exhibited significant dissolution, solubility and analgesic effect compared to the raw Dexi and the control standard diclofenac sodium.

Toxicity screening of a novel poly(methylmethacrylate)-Eudragit nanocarrier on L929 fibroblasts

Translation of innovative drug delivery nanosystems into the market involves an early toxicity screening in the development phase. Previously, we showed that inclusion of the polymer Eudragit (EUD) into poly(methylmethacrylate) (PMMA) nanoparticles (NP) resulted in a novel nanocarrier (PMMA-EUD) with an improved biomedical performance. The safety of this novel nanoparticulate system (PMMA-EUDNPs) was assessed in this work and compared to that of the original PMMANPs by using an integrated approach, comprising in vitro toxicity assessment and NPs physicochemical characterization in water and cell medium. For toxicity assessment several endpoints were analysed, including cell death, oxidative stress, and genotoxicity using L929 fibroblasts. PMMA-EUDNPs proved to be more hydrophobic than the original PMMANPs. Also, charge of both NPs was strongly affected by cell medium. On the other hand, the novel nanosystem was easily uptaken by L929 cells and did not display relevant in vitro cytotoxic or genotoxic effects. On the contrary, PMMANPs were less internalized in cells and proved to be genotoxic, as measured by the micronucleus assay. To conclude, our results provide initial evidence about the safety of the novel and promising PMMA-EUD nanoparticulate system, enabling its further development towards applications for drug delivery.

Polymer–naproxen precipitation by supercritical antisolvent (SAS) process

The non-steroidal anti-inflammatory drug naproxen (NAP) has been coprecipitated with two different biopolymers, Eudragit (EUD) and poly(l-lactic acid) (PLA), by a supercritical antisolvent process (SAS). NAP release profiles were determined in simulated gastric and intestinal fluids in order to identify the best polymer to use for different administration routes. The in vitro release profiles of the NAP–EUD and NAP–PLA systems showed a slower and more controlled release in comparison to the untreated NAP. Moreover, the effects of pressure, temperature, initial concentration of the solution and drug-to-polymer ratio on the particle size and morphology of these drug-polymer systems have been evaluated. Although the morphology was spherical for both kinds of system, the NAP–PLA particles are larger than the NAP–EUD particles. A larger particle size is also obtained on using a lower pressure. However, the temperature did not influence, or only had a slight influence on, the particle size of NAP–PLA systems but it did have an influence on NAP–EUD systems.

A Comparative Evaluation of Drug Release and Permeability of Ethylcellulose, Cellulose Acetate and Eudragit RS100 Microspheres

Present study aims at comparative evaluation of drug release and permeability of diclofenac sodium loaded ethylcellulose (EC), cellulose acetate (CA) and eudragit (EU) microspheres. Microspheres of EC, CA and EU containing diclofenac sodium were prepared by an emulsification-solvent evaporation (oil-in-oil, o/o) method and were investigated for a comparative evaluation of various parameters. The microspheres were found discrete, free flowing, multinucleate, monolithic and spherical. About 5560% of all microspheres prepared were in the size range of -20+30 (715 m) mesh size. The encapsulation efficiency was in the range of 97.1106.4% with various polymers. The wall thickness of microspheres was in the range of 13.69-74.97m which depended on polymer employed and was directly proportional to polymer concentration. Diclofenac release from the microspheres was slow over longer periods of time and depended on the polymer used and coat:core ratio. Release was diffusion controlled and followed first order kinetics. Good linear relationships were observed between percent coat, wall thickness and release rate constant with all the three polymers. The slopes of percent coat vs release rate (k1) plots were found to be 0.4117, 0.2351 and 0.9762; and those of wall thickness (h) vs drug release rate (k1) plots were found 0.2549, 0.1863 and 0.7850 respectively for EC, CA and EU microspheres. The lower the slope the better is the controlling effect. Cellulose acetate exhibited better release-controlling effect than that of ethylcellulose and eudragit. The increasing order of diclofenac release rate and permeability observed with various microspheres was, cellulose acetate < ethylcellulose < eudragit RS100. The possible permeability of drug from the prepared porous micrsopheres could be due to osmotic pressure generated by diclofenac.

Improved Intestinal Absorption of a Poorly Water-Soluble Oral Drug Using Mannitol Microparticles Containing A Nanosolid Drug Dispersion

A nozzle for a spray dryer that can prepare microparticles of water-soluble carriers containing various nanoparticles in a single step was previously developed in our laboratory. To enhance the solubility and intestinal absorption of poorly water-soluble drugs, we used probucol (PBL) as a poorly water-soluble drug, mannitol (MAN) as a water-soluble carrier for the microparticles, and EUDRAGIT (EUD) as a polymer vehicle for the solid dispersion. PBL-EUD-acetone-methanol and aqueous MAN solutions were simultaneously supplied through different liquid passages of the spray nozzle and dried together. PBL-EUD solid dispersion was nanoprecipitated in the MAN solution using an antisolvent mechanism and rapidly dried by surrounding it with MAN. PBL in the dispersion vehicle was amorphous and had higher physical stability according to powder X-ray diffraction and differential scanning calorimetry analysis. The bioavailability of PBL in PBL-EUD S-100-MAN microparticles after oral administration in rats was markedly higher (14- and 6.2-fold, respectively) than that of the original PBL powder and PBL-MAN microparticles. These results demonstrate that the composite microparticles containing a nanosized solid dispersion of a poorly water-soluble drug prepared using the spray nozzle developed by us should be useful to increase the solubility and bioavailability of drugs after oral administration.

Eudraginated polymer blends: A potential oral controlled drug delivery system for theophylline

Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for micromeritic properties, drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl(®)) formulation. Asmanyl(®) tablets showed faster absorption (t(max) 4.0 h) compared to the TPH formulation showing a t(max) value of 8.0 h. The C(max) and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl(®), revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline.

Preparation and Evaluation of Mixture of Eudragit and Ethylcellulose Microparticles Loaded with Ranolazine for Controlled Release

To minimize the unwanted toxic effects of anti-anginal ranolazine by kinetic control of drug release, it was entrapped into gastro-resistant, biodegradable eudragit (EU) and ethyl cellulose (EC) binary blend using phase separation method. Ten formulations were prepared using different polymer blend ratios and solvent. The prepared microparticles were characterized for micromeritic properties, polymer drug compatibility by Fourier Transform Infrared Spectroscopy (FT-IR) and Differential Scannibg Calorimetry (DSC), and surface morphology by Scanning Electron Micrography (SEM). The yield of microparticles was up to 90% and more than 98% of the isolated microparticles are having volume mean diameter of 285 μm. The obtained angle of repose, percentage Carr's index and tapped density values were within the limits indicating good flow properties. The surface morphology revealed that particles were free-flowing, spherical, with minute pores and invert dents on the surface. The prepared microparticles were evaluated for percentage yield, encapsulation efficiency and in vitro release studies. FT-IR and DSC studies showed no chemical interaction between the drug and used polymers The in vitro drug release studies were carried out using pH 1.2 acid buffer and pH 7.4 phosphate buffer. EU acts as an excellent pH-dependent binder and helps to release the drug in the intestine. The drug release kinetics followed different transport mechanisms. Increasing the weight fractions of EU and decreased EC helps to control the drug release from the particles. From the differential (f1) and similarity factor (f2), Formulation F5 was the formulation most similar to the commercially available oral formulation as reference standard. The drug release performance was greatly affected by the materials used in microparticle preparations, which allow absorption in the intestinal tract.

Ammonium methacrylate units polymer content and their effect on acyclovir colloidal nanoparticles properties and bioavailability in human volunteers

Acyclovir (ACV)-Eudragit (EUD) nanoparticles (NPs) were prepared using both EUD RS 100 and RL 100 with different charge density. The effect of charge intensity on particle size, encapsulation efficiency, and in vitro dissolution was assessed. The bioavailability of ACV NP colloids were evaluated in human volunteers, compared with commercial product using a validated LC–MS/MS method with a lower limit of quantification (LLOQ) of 0.02 μg/ml. EUD RL 100 with higher ammonium groups gave smaller NPs than EUD RS 100. The surface charge of the polymer did not affect encapsulation efficiency and in vitro dissolution. In human volunteers, both F2 and F5 colloidal nanosuspensions prepared with EUD RS and RL respectively in drug to polymer ratio 1:3 sustained the oral absorption of ACV, expressed by the significant lower C max, significant delayed T max and the significant higher HV D t 50 % C max . The mean C max of F2, F5, and Zovirax ® were 0.61 ± 0.06, 0.73 ± 0.07 and 0.92 ± 0.21 μg/ml respectively. Furthermore, the AUC 0–12 of F2 and F5 was significantly higher than that of Zovirax ® with values of 4.37 ± 0.88, 5.14 ± 0.87 and 3.21 ± 0.53 μg/ml h respectively. The higher AUC 0–12 for both F2 and F5 reflected high relative bioavailability of 136.2% and 159.9% respectively compared to commercial ACV tablets.

Optimization of Budesonide Compression-Coated Tablets for Colonic Delivery

The purpose of this study was to formulate budesonide (BUD) compression-coated tablets for colonic specific delivery. Pectin and guar gum were used as enzyme-dependent polymers. For comparison purposes, both pH- and time-dependent polymers were also tried. In vitro release studies were carried out at different pH (1.2, 6.8, and 7.4). Therapeutic efficacy of the prepared tablets compared to commercially available capsules and enema were evaluated in trinitrobenzenesulfonic acid-induced rabbit colitis model. In pH-dependent polymers, Eudragit (EUD) S100/EUD L100 (1:1) released 45.58% in the target area (colon). For time-dependent polymers, decreasing cellulose acetate butyrate (CAB) ratio increased the release in both pH 6.8 and 7.4 till it reached 40.58% and 93.65%, respectively, for 25% CAB. In enzyme-dependent polymers, increasing pectin ratio to 75% retarded the release (4.59% in pH 6.8 and 54.45% in pH 7.4) which was significantly enhanced to 99.31% using pectinolytic enzyme. Formula F14 coated with 75% pectin significantly reduced the inflammatory cells in the connective tissue core of the colon of the treated group and significantly decreased myeloperoxidase activity (3.90 U/g tissue weight). This study proved that BUD compression-coated with 75% pectin may be beneficial in the treatment of inflammatory bowel disease.

Polyoxyethylene-poly(methacrylic acid-co-methyl methacrylate) compounds for site-specific peroral delivery

pH-sensitive interpolymer interactions between high molecular weight polyoxyethylene (POE) and poly(methacrylic acid-co-methyl methacrylate) (Eudragit (EUD) L100 or S100) are evidenced and exploited to prepare, from either POE–EUD coevaporates or POE+EUD physical mixtures, both in the 1:1 wt. ratio, compressed matrix tablets, potentially able to deliver the model drug, prednisolone, to sites in the GI tract characterized by specific pHs, such as the jejunum or the ileum. With these devices, drug release is inhibited at pHs lower than the threshold of EUD ionization, whereas at pHs exceeding such a threshold, the matrix undergoes a gradual erosion, which controls the release. A post-compression exposure of tablets to the vapors of appropriate solvents realizes the necessary compaction of matrices, in fact, a high compression force (3 ton) is insufficient, per se, to prevent matrix disintegration in the dissolution medium, whereas such a disintegration is prevented by the treatment with solvent vapors, even with a low compression force (0.3 ton). With the POE+EUD physical mixtures, the exposure to solvent vapors promotes the formation of a layer of POE–EUD complex at the interfaces of the POE and EUD particles in matrix, which inhibits release at pHs lower than that designed for delivery. Both POE and EUD concur to determine the properties of the POE–EUD complex relevant to drug release, indeed, EUD ionization, which elicits matrix erosion and drug release, is favored by the hydrophilic POE. In fact, matrices based on plain EUD exhibit a comparatively low release rate, more suited to an extended delivery to the colon than to a specific delivery to the ileum. Details of the release mechanism are discussed.

Silicone microspheres for pH-controlled gastrointestinal drug delivery

Silicone microspheres containing pH-sensitive hydrogels are prepared, characterized and evaluated for their potential pH-controlled gastrointestinal (GI) drug delivery. The pH-sensitive hydrogels are semi-interpenetrating polymer networks (semi-IPN(s)) made of varying proportions of poly(methacrylic acid-co-methylmethacrylate) (Eudragit (EUD) L100 or EUD S100) and crosslinked polyethylene glycol 8000 (P8000C). Up to 35 wt% hydrogel particles of mean volume diameters from 89 to 123 μm, medicated with 15 wt% prednisolone (PDN), are encapsulated, with 100% efficiency, into morphologically acceptable silicone microspheres in the 500–1000 μm size range, by a modified emulsion vulcanization method. Microspheres are eluted for 9 h with isotonic fluids at pH values increasing from 1.2 to 7.4, to simulate transit across the GI regions. PDN release depends on dissolution medium pH and on hydrogel composition, which determines hydrogel pH-sensitivity. With the P8000C–EUD L100 (1:2) semi-IPN, the release shows a marked peak at pH 6.8. The P8000C–EUD S100 (1:2) semi-IPN causes a gastroprotection and an almost uniform distribution of released drug between media at pH 6.8 and 7.4. With the P8000C–EUD S100 (1:1) semi-IPN, the dose fraction released to gastric fluid increases to match the values for the media at pH 6.8 and 7.4. With the pH-insensitive, highly swelling, P8000C, the largest dose fraction is released to the gastric medium and release is of Fickian type. With semi-IPNs, release depends weakly on the buffer molarity of the dissolution medium, a reduction from 0.13 to 0.032 of which renders the release rate to the media at pH 6.8 and 7.4 more uniform.