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This study is focused to design a colon specific pellet formulation of rifaximin based on the combination of time-dependent and pH sensitive delivery system using Quality-by-Design (QbD) approach for better and promising treatment of inflammatory bowel disease (IBD). An extrusion/spheronization process was utilized for the preparation of core macroparticles using ethyl cellulose (EC) as matrix former and microcrystalline cellulose (MCC) as a spheronizing aid. Two critical process parameters (CPPs) i.e., spheronization time and spheronizer speed were taken as independent factors while aspect ratio, sphericity, carr's index, and particle size were taken as dependent responses to optimize the composition of the core macroparticles. To regulate the drug release, core macroparticles were coated with Eudragit NE40D and Eudragit FS30D to impart time-dependent and pH sensitive release of drug. The optimized coated macroparticles were characterized for drug content and in vitrodrug release in different pH media of stomach and intestine. The coating levels of the inner and outer polymers were further optimized for the time required for 10 %, 50 % and 90 % drug release. The result showed that the 90% of drug of P3 and P4 formulation were found to be released in 10.87 and 13.19hrs respectively. When exposed to Scanning Electron Microscopy the images of coated macroparticles suggested a uniform and smooth coat of polymers over the surface of macroparticles. This formulation reduces the dose and the side effects due to its specific targeting at the site of inflammation makes it a better choice over the tablets. The result indicates that the developed formulation may possibly reduce the dosing frequency and side effects associated with the conventional tablet formulation for the site-specific targeting at inflammation site. [ABSTRACT FROM AUTHOR]

Microfluidics is widely regarded as a leading technology for industrial-scale manufacture of multicomponent, gene-based nanomedicines in a reproducible manner. Yet, very few investigations detail the impact of flow conditions on the biological performance of the product, particularly biocompatibility and therapeutic efficiency. Herein, this study investigated the engineering of a novel lipid-Eudragit hybrid nanoparticle in a bifurcating microfluidics micromixer for plasmid DNA (pDNA) delivery. Nanoparticles of ~150 nm in size, with uniform polydispersity index (PDI = 0.2) and ξ-potential of 5–11 mV were formed across flow rate ratios (FRR, aqueous to organic phase) of 3:1 and 5:1, respectively. The hybrid nanoparticles maintained colloidal stability and structural integrity of loaded pDNA following recovery by ultracentrifugation. Importantly, in vitro testing in human embryonic kidney cell line (HEK293T) revealed significant differences in biocompatibility and transfection efficiency (TE). Lipid-Eudragit nanoparticles produced at FRR 3:1 displayed high cellular toxicity (0–30% viability), compared with nanoparticles prepared at FRR 5:1 (50–100% viability). Red fluorescent protein (RFP) expression was sustained for 24–72 h following exposure of cells to nanoparticles, indicating controlled release of pDNA and trafficking to the nucleus. Nanoparticles produced at FRR 5:1 resulted in markedly higher TE (12%) compared with those prepared at FRR 3:1 (2%). Notably, nanoparticles produced using the bench-scale nanoprecipitation method resulted in lower biocompatibility (30–90%) but higher RFP expression (25–38%). These findings emphasize the need for in-depth analysis of the effect of formulation and flow conditions on the physicochemical and biological performance of gene nanomedicines when transitioning from bench to clinic. Transitioning lipid-Eudragit hybrid nanoparticles from bench-scale nanoprecipitation to industrial-scale microfluidics [ABSTRACT FROM AUTHOR]

Capsules have been investigated as a popular oral dosage form among communities due to their simplicity and ease of production. Capsules that are considered in the gastro-resistance category can be very beneficial due to enhanced drug absorption, improved stability, targeted release, etc. This study investigated the effect of enteric polymers on uncoated hard capsule fabrication and dissolution properties. The polymers used in this study included HPMCPh and Eudragit L100-55. Eight different formulations based on HPMCPh, Eudragit, and gelatin were examined to identify the ideal formulation for the product of uncoated enteric hard capsules with preferred physicochemical and gastro-resistance properties. The results reveal that the capsules containing Eudragit (F1), HPMCPh (F2), Eudragit/HPMCPh/gelatin (F3), and Eudragit/gelatin (F4) are steady within the simulated stomach environment, and drug release does not occur for 120 min. The outcomes demonstrate that, among the proposed formulas, the F4 formula is suitable both in terms of capsulation form and delayed-release properties and shows no microbial growth. The properties of the optimized sample were studied by FTIR, FESEM, tensile strength, humidity, and rheology. The results illustrated that gelatin-based hydrogels with Eudragit (F4) are potential candidates for manufacturing uncoated enteric hard capsules that inhibit drug release in a gastric pH medium and act as a pH-sensitive drug-release system. [ABSTRACT FROM AUTHOR]

Sulfasalazine needs frequent daily dosing and the administration of numerous tablets per day pose challenges to patient compliance, contributing to increased adverse effects and difficulties in disease control. These inconveniences result in less effective treatment for arthritis associated with inflammatory bowel disease i.e. ulcerative colitis etc. To improve drug bioavailability, a delayed-release mechanism that releases the drug at the colon is necessary. To develop and optimize colon-targeted controlled release bilayer tablets coated with pH-dependent polymers. The bilayer tablets containing the immediate release part and sustained release part were developed. The tablets were coated with enteric-coated with Eudragit® S-100 and l -100 to achieve release in the colon. Granule properties and tablets were evaluated. The physicochemical parameters of the tablets were evaluated including, stability study, and drug release in 0.1 N HCl (pH 1.2), pH 6.8 phosphate buffer, pH 7.4 phosphate buffer for 2, 1, and up to 24 h respectively. Radiographic imaging and in vivo pharmacokinetic studies were also done in Rabbits. The bilayer tablets containing immediate and sustained release were successfully developed for the colon targeting. The granule properties were found within the acceptable range indicating good flow properties. The physicochemical properties of the tablets were also found acceptable. The tablets did not show release in 0.1 N HCl and 6.8 phosphate buffer but drug release was found under control in the 7.4 pH buffer. Sulfasalazine coated bilayer tablets were found stable and no significant changes were observed in the stability studies. Based on the X-ray studies, the formulated tablet remained discernible in the stomach, small intestine, and colon for a duration of up to 24 h. Finally, by the 32nd hour, the tablet was no longer visible in the X-ray examination, leading to the conclusion of complete drug release. The drug concentration in plasma remained within the therapeutic range for up to 24 h in vivo. These novel formulations present substantial advantages, providing prolonged targeted drug release and reducing systemic adverse effects. The results suggest promising potential for treating arthritis in Inflammatory bowel disease (IBD) patients, offering a solution to current delivery systems. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: This study aims to formulate a ketoconazole patch containing electrospun nanofibres and enhance the solubility due to the increased particle surface using the electrospinning method. Methods: The Design-Expert version13 software was used in experimental designing, to ensure an efficient nanofiber preparation process. Several nanofiber formulations were prepared with different concentrations of drug and polymers. In this study, Ketoconazole was selected as the model drug, ketoconazole is widely used as an antifungal drug in the treatment of fungal infections. Eudragit and Polyethylene glycol polymers were used with ketoconazole to formulate electrospun nanofibers. Then Ketoconazole nanofibers were investigated and evaluated chemically and morphologically by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Results: Utilizing the electrospinning method, Ketoconazole electrospun nanofiber was successfully fabricated. The produced ketoconazole-loaded nanofibers mat was formulated as a dermal patch. The Eudragit and polyethylene glycol polymers revealed good characteristics that led to the production of uniform ketoconazole nanofibers. The prepared patch showed good physical and mechanical properties. The SEM results Images for the produced nanofiber mat showed good nanofiber distribution and no beads formation with several fiber diameter sizes, while Fourier Transform Infrared Spectroscopy findings revealed the conjugation between polymers and ketoconazole pure powder, the major characteristic peaks of ketoconazole appeared in the FTIR spectrum. Formula 7 showed minimum nanofibers diameter with maximum entrapment efficiency. Conclusions: In this study, the use of the electrospinning method completed the formulation of a dermal patch containing antifungal nanofibers successfully. Using design expert software to ensure maximum optimization, two biocompatible polymers were used, Eudragit E100 and PEG 600 to formulate ketoconazole nanofibers. The formulated dermal patch could be promising for pharmaceutical antifungal applications. [ABSTRACT FROM AUTHOR]

In this paper, rhodamine 6G and carborane were used as raw materials, and four fluorescent polymers were prepared by one-pot method, namely L100-55 fluorescent polymer (L100-55-B), EPO polymer (EPO-B), RS polymer (RS) and RL polymer (RL). The problem of poor water solubility of carborane was solved and the biocompatibility of rhodamine 6G-nido-carborane was improved. By simulating the release of polymers in different gastrointestinal environments, it was found that the release rate of drugs in the four coating materials was slow and controllable, with good bioavailability. Affected by the properties of the resin, L100-55 and EPO coating had the best release effect in the gastrointestinal tract. In the zeta potential test, the absolute potential values of L100-55-B and EPO-B are stable, both up to 30 mV. Transmission electron microscopy revealed that the drug was uniformly dispersed in the drug carrier material and wrapped into nanospheres with particle sizes below 500 nm. Hela cells were imaged in different acidic environments, and the results showed that the polymer had good affinity with target cells and was closely connected to target cells, indicating good biocompatibility and targeting of the polymer. This design not only solves the bioavailability problem of rhodamine 6G-nido-carborane, but also has a good fluorescence targeting effect. Rhodamine 6G-nido-carborane coated by four eudragits, L100-55, EPO, RS, and RL, are released in the gastrointestinal environment. Cell imaging under a microscope shows that L100-55-B and EPO-B have a strong affinity for Hela cells. Four coating pathways, the released rhodamine 6G-nido-carborane targets tumor cells and exerts inhibitory effects. 1. The bioavailability and water solubility of carborane derivatives have been improved. 2. Rhodamine 6G is used to make the complex visible in vivo, which is convenient for monitoring the drug distribution. 3. Acrylic resin coating can change drug release performance. 4. Hela cell imaging experiments display excellent cellular permeability. [ABSTRACT FROM AUTHOR]

The coating process for solid dosage forms is widely used in the pharmaceutical industry but presents challenges for small-scale production, needed in personalized medicine and clinical or galenic settings. This study aimed to evaluate immersion coating, a cost-effective small-scale method, for enteric-coated gelatin capsules using standard equipment. Two enteric coating polymers and different polymer concentrations were tested, along with API solubility. Results were compared with commercially available enteric capsule shells. Successful preparation of enteric coating capsules via immersion necessitates a comprehensive grasp of API and enteric polymer behavior. However, utilizing commercially available enteric capsule shells does not guarantee ease or robustness, as their efficacy hinges on the attributes of the active ingredient and excipients. Notably, coating with Eudragit S100 stands out for its superior process robustness, requiring minimal or no development time, thus representing the best option for small-scale enteric capsule production. [ABSTRACT FROM AUTHOR]

(Cilostazol is considered a potential anti-platelets drug exhibiting also antithrombotic effects. Unfortunately, cilostazol shows low oral bioavailability due to its low aqueous solubility. Nanofibers are a promising new class of drug delivery materials that can improve the solubility of poorly soluble medications and prolong their release, thereby creating a gastro-retentive delivery system. This can be achieved by appropriate picking of polymers in the fabrication of the nanofibers . Consequently, the goal of this work was to create eudragit/ethyl cellulose-based nanofibers for enhancing and managing the release of the medication cilostazol. Scanning electron microscopy (SEM) was used to characterize the nanofibers' shape. Also floating behavior, drug content, drug solubility and drug release profile were determined for evaluation of the nanofiber. The Scanning electron microscopy (SEM) showed that the cilostazol-loaded nanofibers were smooth and uniform. Solubility study showed that nanofibers enhanced the cilostazol aqueous solubility by more than ten folds. The floating study showed that the nanofibers developed extended floating time. Drug content was satisfactory and reached 87.6%. Eudragit/ethyl cellulose nanofiber enhanced the solubility of cilostazol reaching 43.5% while only 11.6% for the unprocessed cilostazol after 24 hours exhibiting also sustained drug release profile). [ABSTRACT FROM AUTHOR]

The main purpose of this study is to design Cefpodoxime proxetil (CFP) loaded Eudragit RS 100 (ERS) nanoparticles to provide prolonged drug release, the enhanced oral efficacy of the drug at a lower oral dose. CFP-loaded nanoparticles are prepared by the single-emulsion solvent evaporation method with different drug:polymer ratios, F1 (CFP:ERS=1:1) and F2 (CFP:ERS=1:2). Physicochemical characterization, antibacterial activity, cytotoxicity profiles of nanoparticles are examined. F1 and F2 nanoparticles have a particle size of 236.70±3.05 and 258.87±11.32 nm, spherical shape, and a porous surface under SEM. The zeta potential values of F1 and F2 nanoparticles were 22.13±1.01 and 25.80±2.01 mV, and the encapsulation efficiencies were 34.37±3.71% and 55.78±3.52%, respectively. Since F2 nanoparticles have a smaller particle size, higher zeta potential, and encapsulation efficiency, this formulation was chosen as superior, and the subsequent experiments were continued with this formulation. The antibacterial activity of F2 nanoparticles against E.coli was found to be 2 times more effective than CFP. Cytotoxicity studies revealed that the cell viabilities in BEAS-2B and HepG2 cells were higher with the exposure to CFP nanoparticles (200 µg/ml) compared to CFP (100 µg/ml) alone. CFP nanoparticles have excellent efficacy and a cytocompatible profile in inhibiting the growth of bacteria compared to free CFP. [ABSTRACT FROM AUTHOR]

Abstract The therapeutic potential of medicinal plants is known as an alternative in treatment of human affections; in effect, the conventional application of these medicinal sources has several limitations like low bioavailability, solubility and stability, which affect its pharmacological efficacy. In recent decades, extraordinary advances have been made in new drug delivery systems using nanocarriers. This work consisted in determining the in vitro antifungal activity of the methanolic extract of Euphorbia tirucalli formulated in polymeric nanoparticles. The antifungal activity was determined by the microdilution method in 96-well microplates, applying nanoparticles loaded with plant extract (NP-Ext) obtained by nanoprecipitation on clinical isolates of Trichophyton rubrum and T. interdigitalis. Regarding the nanoparticles, the lots used did not present significant differences in their physicochemical characteristics, with a size of 91.885 ± 1.621nm, polydispersity index of 0.152 ± 0.025 and Z-potential of -6.047 ± 0.987. The quantification of the extract in the polymeric matrix was determined by infrared spectroscopy (FTIR), where an efficiency and encapsulation percentage of 22.15 ± 0.82 and 2.95 ± 0.11, respectively, were obtained. The in vitro antifungal activity of the crude and formulated extract was obtained calculating the Minimum Inhibitory Concentration (MIC) of each one; a MIC of 125 µg/mL was obtained against T. rubrum and T. interdigitalis with the crude extract, while a MIC value of 55.55 and 0.1 µg/mL was obtained with NP-Ext, respectively, against these same. Conclusions: biological activity is closely linked to the phytochemical profile of the extract; while the improvement of said potential with the NP-Ext with the dosage form was directly related to the physicochemical characteristics of the nanocarrier.

Acetaminosalol labeling reaction with technetium‐99m was optimized, and the radiocomplex was obtained in a high radiochemical yield of 98.9 ± 0.6% and high stability (>30 h). The tracer was characterized, and its binding to the PPARγ receptor was assessed in silico. To reduce radiation exposure to non‐target organs and increase accumulation in the colon, the tracer was formulated as pH‐sensitive microspheres with a mean particle size of 201 ± 2.1 μm, a polydispersity index of 0.18, a 25.3 ± 3.6 zeta potential, and 98.6 ± 0.33% entrapment efficiency. The system suitability was assessed in vivo in normal and ulcerative rats, and the biodistribution profile in the colon showed 56.5 ± 1.4% localization within 4 h. Blocking study suggested the selectivity of the tracer to the target receptor. Overall, the reported data encouraged the potential use of the labeled microspheres to target ulcerative colitis. [ABSTRACT FROM AUTHOR]

The objective of the study was to fabricate tailored extended‐release tablets of blood thinner Ticagrelor as once‐daily dosing using additive manufacturing for better compliance in heart failure therapy. The solid work design of the tablet was printed using hot melt extrusion (HME) based 3D printing by optimized mixture of Eudragit RS‐100, plasticizer and drug for producing extrudable and printable filaments. FTIR and TGA results showed no covalent interaction among ingredients and no decomposition during HME process, respectively. Friability, weight variation, assay and content uniformity tests met USP requirements, while the mean hardness of the tablets was calculated in a value between 40 and 50 kg. According to DSC and XRD results, the crystallinity state of the Ticagrelor was converted to an amorphous one in the tablet matrix. Smooth surfaces with multiple deposited layers were observed using SEM. In comparison, the maximum Ticagrelor release of 100% after 120 min from Brilinta® tablets was decreased to 97% in 400 min from the 3D tablet at infill of 90%. Korsmeyer‐Peppas kinetic model showed the drug release mechanism is affected by diffusion and swelling. In general, fabrication of the extended‐release 3D printed tablet of Ticagrelor using HME‐based‐additive manufacturing has the potential to provide specific doses with tailored kinetic release for personalized medicine, improving adherence at point‐of‐care. [ABSTRACT FROM AUTHOR]

Targeted drug delivery is achieving great success in cancer therapy due to its potential to deliver drugs directly to the action site. Terbinafine hydrochloride (TER) is a broad-spectrum anti-fungal drug that has been found to have some potential anti-tumor effects in the treatment of colon cancer. We aimed here to design and develop pH-sensitive Eudragit (Eud)-coated mesoporous silica nanostructures (MSNs) to control drug release in response to changes in pH. The diffusion-supported loading (DiSupLo) technique was applied for loading TER into the MSNs. The formulation was optimized by a D-optimal design, which permits the concurrent assessment of the influence of drug/MSN%, coat concentration, and MSN type on the drug entrapment efficiency (EE) and its release performance. The optimal formula displayed a high EE of 96.49%, minimizing the release in pH 1.2 to 16.15% and maximizing the release in pH 7.4 to 78.09%. The cytotoxicity of the optimal formula on the colon cancer cells HT-29 was higher than it was with TER alone by 2.8-fold. Apoptosis in cancer cells exposed to the optimum formula was boosted as compared to what it was with the plain TER by 1.2-fold and it was more efficient in arresting cells during the G0/G1 and S stages of the cell cycle. Accordingly, the repurposing of TER utilizing Eud/MSNs is a promising technique for targeted colon cancer therapy. [ABSTRACT FROM AUTHOR]

Objectives: Oral steroids are commonly prescribed to children. Steroids have a strong bitter taste that limits their oral acceptance in children. The objective of this study was to formulate a pediatric-friendly and palatable oral dosage form of steroids. Materials and Methods: Solid dispersions of dexamethasone were prepared using polyethylene glycol, pectin, and Eudragit as carrier polymers, and chocolate as a flavoring agent. Taste masking efficiency was evaluated by healthy volunteers to select the best formula. The selected formula was pressed into chewable tablets with varying amounts of sweeteners. Chewable tablets were evaluated for palatability, hardness, and chewing index. The typical application of the taste masking approach was confirmed using prednisolone. Results: Eudragit-based solid dispersions were effective in dexamethasone taste masking. Using 40% mannitol resulted in palatable tablets with acceptable hardness and chewing difficulty. The effectiveness of the taste masking approach was successfully used to prepare prednisolone chewable tablets. However, an increase in the carrier: drug ratio and a change in the flavor to pineapple were necessary to achieve maximum palatability of prednisolone chewable tablets. Conclusion: Eudragit solid dispersion is an effective method for the taste masking highly bitter steroids. The solid dispersion was successfully pressed into a palatable, easy-to-chew, and pediatric-friendly chewable tablet dosage form. The carrier: drug ratio and the choice of flavoring agent are crucial factors in improving tablet palatability. [ABSTRACT FROM AUTHOR]

3D printing is heavily researched in the pharmaceutical field over the last two decades and, more recently, in cosmetics research. Fused deposition modelling (FDM) is one of many methods of printing. The FDM process allows printing structures in various sizes and shapes by using read-ymade filaments and/or filaments loaded with active ingredients produced by various methods. However, using FDM for producing topical applications for the skin is limited. Therefore, in this work, FDM is used to print topical patches containing salicylic acid for acne treatment. By utilizing Eudragit EPO as the polymer, the patch can be printed at a lower temperature, safeguarding the integrity of salicylic acid. The patch shows good mechanical strength, and successful in vitro release of salicylic acid is achieved. This research signifies the potential of 3D printing for efficient and customizable skincare applications.

Nanoparticles based TDDS was employed to overcome the adverse effects of oral contraceptives. A transdermal patch of Ethinyl Estradiol (EE) nanoparticles was aimed to provide sustained release of the drug and lower dosage frequency. The patch was designed with Eudragit-based polymeric films or EE-loaded chitosan nanoparticles poured onto a polyvinyl alcohol backing membrane, with a non-ionic surfactant (span-20) and a plasticizer (n-butyl phthalate) using solvent evaporation method. Nanoparticles were analyzed for their size, morphology, yield and entrapment efficiency. The patches were analyzed for their folding endurance, thickness, weight, drug content, in vitro release pattern, FTIR and DSC. All patches were transparent, having a uniform, smooth surface. The folding endurance of all the patches indicated optimum flexibility. In vitro, release and Ex-Vivo permeation studies showed that F1 containing nanoparticles exhibited the most optimum drug release in 72h (97.6%). The release pattern demonstrated was diffusion controlled. FTIR, DSC studies indicated no interaction between drug and excipients. The accelerated stability studies were performed at 40ᵒC and 70% relative humidity for six months. The product was found stable. The developed patches of EE nanoparticles were expected to improve patient compliance by reducing dose frequency and provide optimum therapy by sustained drug release for contraception. [ABSTRACT FROM AUTHOR]

Purpose: In the present study, we aimed to optimize, formulate and characterize Eudragit-based nanosuspension of Ganciclovir (GCV-NPs) as a carrier for ocular delivery. GCV is having a potential role in the treatment of herpes simplex keratitis caused by herpes simplex virus (HSV). The topical delivery of GCV is valuable for treating the HSK but it is limited due to its hydrophilic character. Hence, the purpose of the work was to develop nanosuspension of GCV with the help of a hydrophobic polymer Eudragit RL 100 in order to enhance the corneal permeation and to achieve sustained release of medication. Methods: The GCV-NPs was formulated using nanoprecipitation method and the formula was optimized using central composite design. The optimized formulation was characterized for particle size (PS), zeta potential (ZP), entrapment efficiency (EE), polydispersity index (PDI), scanning electron microscopy (SEM), pH, in vitro drug release study and ex vivo transcorneal permeation study. Results: The GCV-NPs were successfully developed using nanoprecipitation method. The optimized GCV-NPs have an average particle size of 260.8 ± 2.05 nm and drug entrapment efficiency of 51.06 ± 0.36%. The ZP and PDI were found to be − 10 ± 6.45 and 0.158 ± 0.02 respectively. The SEM images revealed a spherical shape for the optimized nanoparticles. The formulation has a pH of 6.96 ± 0.20. When compared with GCV solution, the optimized GCV-NPs exhibited a sustained release pattern and enhanced corneal permeation. Conclusion: The formulated GCV-NPs have demonstrated several advantages like suitable pH, enhanced permeation and sustained release of medication. These findings indicate the potential role of GCV-NPs in ocular drug delivery. [ABSTRACT FROM AUTHOR]

Exclusive physicochemical and biological properties of carbon allotrope graphene have attracted the peer attention of researchers for the synthesis and development of newer topical remedies including films, scaffolds, microspheres, and hydrogels. Here, graphene nanoplatelets (GN) were embedded into a different ratio of polymeric ERL100/ERS100 solution and fabricated in the form of a scaffold through the electrospinning process. FTIR spectra displayed characteristic similar peaks present both in GN and GN-loaded scaffold owing to the compatibility of GN and polymeric mixture. XRD curve revealed a distinct GN peak at nearly 26° whereas from DSC/TGA thermal stability was observed between polymers and graphene nanoplatelets. FESEM images showed ultrathin architecture of GN-loaded scaffold in a range of 280 ± 90 nm. The fabricated scaffold exhibited hydrophilicity (contact angle 48.8 ± 2.8°) and desirable swelling index (646% in skin pH media) which were desired criteria for the scaffold for topical application. In vitro, antifungal activity was conducted through the broth microdilution method against different virulent dermatophytes i.e., Microsporum gypseum, M. canis, M. fulvum, and Trychophyton rubrum. For in vivo evaluation, T. rubrum inoculum was applied on the dorsal surface of each group of Swiss albino mice, and the degree and intensity of mycelial growth or erythema on skin surfaces was visually investigated. The study depicted complete signs of cure after 14 days of application of G3-loaded scaffold on the infected dorsal site. Hence graphene-loaded scaffold represented a possible alternative for the treatment of topical fungal infections caused by dermatophytes. [ABSTRACT FROM AUTHOR]

To design and develop a nanoformulation from isolated quercetin (QT) from the Annona reticulata Linn leaves to enhance therapeutic index, solubility, bioavailability, toxicity mitigation, pharmacological activity improvement, and prevention of physical and chemical degradation of antidiabetic lead compounds. Bio-flavonoids are gaining popularity in diabetes and other therapeutic research due to their various pharmacological and biological effects. QT is one of several beneficial flavonoids, has amazing hypoglycemic effects, with significant improvement, stabilization of long-term insulin secretion, and regeneration of human islets in the pancreas without causing severe health risks. However, poor solubility, biological milieu instability, limited permeation, short biological half-life, and low bioavailability prevent its widespread use in anti-diabetic research. This novel approach of polymeric nanoformulation of QT will improve the bioavailability and enhance its antidiabetic activity. The effectiveness of QT-loaded Eudragit L-100 (EDL) nanoparticles (NPs) against hyperglycemia in streptozotocin-induced type 2 diabetic rats was investigated in this work. QT/EDLNPs were designed by Box–Behnken Design and prepared by a sonication-assisted emulsification solvent evaporation process. The optimized QT/EDLNPs formulation was administered orally for 21 days to streptozotocin-induced diabetic rats. The QT/EDLNPs demonstrated significant antidiabetic effects comparable to the currently available anti-diabetic drug Glibenclamide. Thus, the approach provides an effective oral medicine for diabetes management with a lower dose and dosing frequency that is also patient compliant. These findings suggest that QT/EDLNPs is an effective oral medicine for diabetes management with a lower dose and dosing frequency that is also patient compliant. This study also investigates a fantastic alternative method for creating brand-new polymeric NPs that serve as bioactive compound delivery systems.Journal instruction requires a city for affiliations; however, these are missing in affiliation 2. Please verify if the provided city is correct and amend if necessary.City for affiliation 2 is Dibrugarh.It is correctPlease confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author Given name: [Mohammad Zaki], Last name [Ahmad], Given name: [Ratna Jyoti], Last name [Das].The author names are presented accurately.It is confirmed [ABSTRACT FROM AUTHOR]

The effect of Eudragit RSPO on the photostability of venlafaxine in a physical mixture and as a melt was studied. A validated ultra-high-performance liquid chromatography mass spectrometry method was used to determine the content of venlafaxine alongside degradation products. The most likely structures of the degradation products were determined by mass spectrometry. The samples were evaluated before and after exposure to ultraviolet A by differential scanning calorimetry and scanning electron microscopy. The kinetic parameters of the decomposition of venlafaxine in the physical mixture and melt form were calculated and comparable to those of venlafaxine as an active pharmaceutical ingredient. The results indicate that the process of venlafaxine decomposition is more than three times slower in the venlafaxine–eudragit melt than in its physical mixture with eudragit and its pure form. The strong photoprotective nature of the tested polymer against venlafaxine in the melt form was also confirmed by differential scanning calorimetry and scanning electron microscopy. [ABSTRACT FROM AUTHOR]

The coating process for solid dosage forms is widely used in the pharmaceutical industry but presents challenges for small-scale production, needed in personalized medicine and clinical or galenic settings. This study aimed to evaluate immersion coating, a cost-effective small-scale method, for enteric-coated gelatin capsules using standard equipment. Two enteric coating polymers and different polymer concentrations were tested, along with API solubility. Results were compared with commercially available enteric capsule shells. Successful preparation of enteric coating capsules via immersion necessitates a comprehensive grasp of API and enteric polymer behavior. However, utilizing commercially available enteric capsule shells does not guarantee ease or robustness, as their efficacy hinges on the attributes of the active ingredient and excipients. Notably, coating with Eudragit S100 stands out for its superior process robustness, requiring minimal or no development time, thus representing the best option for small-scale enteric capsule production.

In this work, we report the use of the hot melt extrusion method in harsh extrusion conditions, i.e., screw rotation speed of 250 rpm, temperature above 100 °C, and two mixing zones, in order to obtain an amorphous dispersion of an active pharmaceutical ingredient (API) that is sparingly soluble in water. As a polymer matrix Eudragit EPO (E-EPO) and as an API ibuprofen (IBU) were used in the research. In addition, the plasticizer Compritol 888 ATO (COM) was tested as a factor potentially improving processing parameters and modifying the IBU release profile. In studies, 25% by weight of IBU, 10% of COM and various extrusion temperatures, i.e., 90, 100, 120, 130, and 140 °C, were used. Hot melt extrusion (HME) temperatures were selected based on the glass transition temperature of the polymer matrix (Tg = 42 °C) and the melting points of IBU (Tm = 76 °C) and COM (Tm = 73 °C), which were tested by differential scanning calorimetry (DSC). The thermal stability of the tested compounds, determined on the basis of measurements carried out by thermogravimetric analysis (TGA), was also taken into account. HME resulted in amorphous E-EPO/IBU solid dispersions and solid dispersions containing a partially crystalline plasticizer in the case of E-EPO/IBU/COM extrudates. Interactions between the components of the extrudate were also studied using infrared spectroscopy (FTIR-ATR). The occurrence of such interactions in the studied system, which improve the stability of the obtained solid polymer dispersions, was confirmed. On the basis of DSC thermograms and XRPD diffractograms, it was found that amorphous solid dispersions were obtained. In addition, their stability was confirmed in accelerated conditions (40 °C, 75% RH) for 28 days and 3 months. The release profiles of prepared tablets showed the release of 40% to 63% of IBU from the tablets within 180 min in artificial gastric juice solution, with the best results obtained for tablets with E-EPO/IBU extrudate prepared at a processing temperature of 140 °C. [ABSTRACT FROM AUTHOR]

Eluxadoline (ELD), a recently approved drug, exhibits potential therapeutic effects in the management and treatment of IBS-D. However, its applications have been limited due to poor aqueous solubility, leading to a low dissolution rate and oral bioavailability. The current study's goals are to prepare ELD-loaded eudragit (EG) nanoparticles (ENPs) and to investigate the anti-diarrheal activity on rats. The prepared ELD-loaded EG-NPs (ENP1-ENP14) were optimized with the help of Box–Behnken Design Expert software. The developed formulation (ENP2) was optimized based on the particle size (286 ± 3.67 nm), PDI (0.263 ± 0.01), and zeta potential (31.8 ± 3.18 mV). The optimized formulation (ENP2) exhibited a sustained release behavior with maximum drug release and followed the Higuchi model. The chronic restraint stress (CRS) was successfully used to develop the IBS-D rat model, which led to increased defecation frequency. The in vivo studies revealed a significant reduction in defecation frequency and disease activity index by ENP2 compared with pure ELD. Thus, the results demonstrated that the developed eudragit-based polymeric nanoparticles can act as a potential approach for the effective delivery of eluxadoline through oral administration for irritable bowel syndrome diarrhea treatment. [ABSTRACT FROM AUTHOR]

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition in the colon that includes ulcerative colitis and Crohn’s disease. Dexamethasone is a steroid anti-inflammatory drug that can be used in IBD therapy. This study aims to obtain an optimum formulation of a dexamethasone drug delivery system for IBD treatment and to investigate its release profile based on an in vitro dissolution test. Dexamethasone was formulated as a double-coated tablet in combination with a probiotic L. acidophilus and B. longum mixture (1:1). The core tablets were produced using the wet granulation method, after which they were coated with pectin 4% b/v on the inner coat and a mixture of Eudragit L100 and S100 (1:4) on the outer coat. Three different core tablet formulas were prepared by varying the concentration of probiotics at 0%, 16% and 40% (F1, F2, and F3, respectively). The cumulative drug release of F1, F2 and F3 in HCl 0.1 N pH 1.2 for 2 hours were 42.92 ± 1.55%, 39.41 ± 4.10%, and 39.39 ± 1.63%, respectively, while in the phosphate buffer pH 6.8 they were 102.83 ± 1.56%, 105.08 ± 1.70%, and 98.81 ± 3.37% respectively, after 12 hours. From the results, we conclude that all formulas could be promising candidates for developing colon-targeted drug delivery.

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Targeted drug delivery is achieving great success in cancer therapy due to its potential to deliver drugs directly to the action site. Terbinafine hydrochloride (TER) is a broad-spectrum anti-fungal drug that has been found to have some potential anti-tumor effects in the treatment of colon cancer. We aimed here to design and develop pH-sensitive Eudragit (Eud)-coated mesoporous silica nanostructures (MSNs) to control drug release in response to changes in pH. The diffusion-supported loading (DiSupLo) technique was applied for loading TER into the MSNs. The formulation was optimized by a D-optimal design, which permits the concurrent assessment of the influence of drug/MSN%, coat concentration, and MSN type on the drug entrapment efficiency (EE) and its release performance. The optimal formula displayed a high EE of 96.49%, minimizing the release in pH 1.2 to 16.15% and maximizing the release in pH 7.4 to 78.09%. The cytotoxicity of the optimal formula on the colon cancer cells HT-29 was higher than it was with TER alone by 2.8-fold. Apoptosis in cancer cells exposed to the optimum formula was boosted as compared to what it was with the plain TER by 1.2-fold and it was more efficient in arresting cells during the G0/G1 and S stages of the cell cycle. Accordingly, the repurposing of TER utilizing Eud/MSNs is a promising technique for targeted colon cancer therapy.

An attempt was made to conquer the limitation of orally administered nanoparticles for the delivery of budesonide to the colon. The ionic gelation technique was used to load budesonide on chitosan nanoparticles. The nanoparticles were investigated in terms of size, zeta potential, encapsulation efficiency, shape and drug release. Then, nanoparticles were pelletized using the extrusion–spheronization method and were investigated for their size, mechanical properties, and drug release. Pellets were subsequently coated with a polymeric solution composed of two enteric (eudragit L and S) and time-dependent polymers (eudragit RS) for colon-specific delivery. All formulations were examined for their anti-inflammatory effect in rats with induced colitis and the relapse of the colitis after discontinuation of treatment was also followed. The size of nanoparticles ranged between 288 ± 7.5 and 566 ± 7.7 nm and zeta potential verified their positive charged surface. The drug release from nanoparticles showed an initial burst release followed by a continuous release. Pelletized nanoparticles showed proper mechanical properties and faster drug release in acidic pH compared with alkaline pH. It was interesting to note that pelletized budesonide nanoparticles released the drug throughout the GIT in a sustained fashion, and had long-lasting anti-inflammatory effects while rapid relapse was observed for those treated with conventional budesonide pellets. It seems that there is a synergistic effect of nanoformulation of budesonide and the encapsulation of pelletized nanoparticles in a proper coating system for colon delivery that could result in a significant and long-lasting anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

pH-responsive polyelectrolytes, including methacrylate-based anionic copolymers (MACs), are widely used as enteric coatings and matrices in oral drug delivery. Despite their widespread use in these macroscopic applications, the molecular understanding of their use as stabilizers for nanoparticles (NPs) is lacking. Here, we investigate how MACs can be used to create NPs for therapeutic drug delivery and the role of MAC molecular properties on the assembly of NPs via flash nanoprecipitation. The NP size is tuned from 59 to 454 nm by changing the degree of neutralization, ionic strength, total mass concentration, and the core-to-MAC ratio. The NP size is determined by the volume of hydrophilic domains on the surface relative to the volume of hydrophobic domains in the core. We calculate the dimensions of the hydrophobic NP core relative to the thickness of the polyelectrolyte layer over a range of ionizations. Importantly, the results are shown to apply to both high-molecular-weight polymers as core materials and small-molecule drugs. The pH responsiveness of MAC-stabilized NPs is also demonstrated. Future development of polyelectrolyte copolymer-stabilized nanomedicines will benefit from the guiding principles established in this study. [ABSTRACT FROM AUTHOR]

Objective(s): Folic acid is an essential vitamin, labile to hydrolysis in the acidic environment of the stomach with low water solubility and bioavailability. In order to solve these problems, enteric oral folic acid-loaded microfibers with a pH-sensitive polymer by electrospinning method were prepared.Materials and Methods: Electrospinning was performed at different folic acid ratios and voltages. Fibers were evaluated in terms of mechanical strength, acidic resistance, and drug release. Additionally, DSC (Differential Scanning Calorimetry), FTIR (Fourier-transform infrared spectroscopy), and XRD (X-ray diffraction) analyses were performed on the optimal formulation. Results: Drug ratio and voltage had a considerable effect on fibers’ entrapment efficiency, acid resistance, and mechanical strength. Based on the obtained results, the optimum formulation containing 1.25% of the drug/polymer was prepared at 18 kV. The entrapment efficiency of the optimal sample was above 90% with an acid resistance of higher than 70%. The tensile test confirmed the high mechanical properties of the optimum microfiber. DSC and XRD tests indicated that folic acid was converted to an amorphous form in the fiber structure and the FTIR test confirmed the formation of a chemical bond between the drug and the polymer. The release of the drug from the optimal fiber was about 90% in 60 min.Conclusion: In conclusion, the optimal formulation of folic acid with proper mechanical properties can be used as a candidate dosage form for further bioavailability investigations.

Diarrhea is a globally major problem especially Escherichia coli induced diarrhea becoming fatal nowadays in developing countries. Colon-targeted chitosan microspheres (Ms) comprising of lipase‑zinc and lipase‑copper complexes were prepared, loaded with Attapulgite (Cts-Li-Zn-ATG/Ms and Cts-Li-Cu-ATG/Ms) for the treatment of bacterial diarrhea. Thin layer chromatography (TLC) and Fourier-transform infrared spectroscopy (FTIR) studies were used for confirmation of proposed lipase-metal complexes. Ms showed particle size range 18 ± 0.24 to 23 ± 0.83 μm, zeta potential −13.7 ± 0.71 to −29.3 ± 1.34 mV, PDI 0.5 ± 0.04 to 1.0 ± 0.07 and hemolytic activity was found to be <5 ± 1.25 %. After coating with Eudragit S-100 for colon targeting, in-vitro % drug release of ATG at pH 7.4 was 80 ± 0.21 % for Eud-Cts-Li-Zn-ATG/Ms while it was increased to 83 ± 0.54 % for Eud-Cts-Li-Cu-ATG/Ms within 7 h, respectively. In-vivo anti-diarrheal activity of Eud-Cts-Li-Zn-ATG/Ms and Eud-Cts-Li-Cu-ATG/Ms was performed by oral challenge on albino mice having infectious diarrhea colonized with E. coli. Results revealed significant anti-diarrheal effect of proposed Eud-Cts-Li-Cu-ATG/Ms in terms of weight gain from 24 ± 0.12 g to 26.05 ± 0.31 g, which was 2-fold increase as compared to Eud-Cts-Li-Zn-ATG/Ms. Conclusively, Eud-Cts-Li-Cu-ATG/Ms provides an innovative alternate for the treatment of bacterial diarrhea with additional support of chitosan and lipase for nutritional support and immunity which was compromised in diarrheal patients. Showing preparation of lipase-metals complex/chitosan microspheres loaded with attapulgite used for the treatment of E. coli- induced diarrhea in albino mice. [Display omitted] [ABSTRACT FROM AUTHOR]

Exclusive physicochemical and biological properties of carbon allotrope graphene have attracted the peer attention of researchers for the synthesis and development of newer topical remedies including films, scaffolds, microspheres, and hydrogels. Here, graphene nanoplatelets (GN) were embedded into a different ratio of polymeric ERL100/ERS100 solution and fabricated in the form of a scaffold through the electrospinning process. FTIR spectra displayed characteristic similar peaks present both in GN and GN-loaded scaffold owing to the compatibility of GN and polymeric mixture. XRD curve revealed a distinct GN peak at nearly 26° whereas from DSC/TGA thermal stability was observed between polymers and graphene nanoplatelets. FESEM images showed ultrathin architecture of GN-loaded scaffold in a range of 280 ± 90 nm. The fabricated scaffold exhibited hydrophilicity (contact angle 48.8 ± 2.8°) and desirable swelling index (646% in skin pH media) which were desired criteria for the scaffold for topical application. In vitro, antifungal activity was conducted through the broth microdilution method against different virulent dermatophytes i.e., Microsporum gypseum, M. canis, M. fulvum, and Trychophyton rubrum. For in vivo evaluation, T. rubrum inoculum was applied on the dorsal surface of each group of Swiss albino mice, and the degree and intensity of mycelial growth or erythema on skin surfaces was visually investigated. The study depicted complete signs of cure after 14 days of application of G3-loaded scaffold on the infected dorsal site. Hence graphene-loaded scaffold represented a possible alternative for the treatment of topical fungal infections caused by dermatophytes.

Since their introduction to pharmacotherapy, proton pump inhibitors (PPIs) have been widely used in the treatment of numerous diseases manifested by excessive secretion of gastric acid. Despite that, there are still unmet needs regarding their availability for patients of all age groups. Their poor stability hinders the development of formulations in which dose can be easily adjusted. The aim of this review is to describe the discovery and development of PPIs, discuss formulation issues, and present the contemporary solutions, possibilities, and challenges in formulation development. The review outlines the physicochemical characteristics of PPIs, connects them with pharmacokinetic and pharmacodynamic properties, and describes the stability of PPIs, including the identification of the most important factors affecting them. Moreover, the possibilities for qualitative and quantitative analysis of PPIs are briefly depicted. This review also characterizes commercial preparations with PPIs available in the US and EU. The major part of the review is focused on the presentation of the state of the art in the development of novel formulations with PPIs covering various approaches employed in this process: nanoparticles, microparticles, minitablets, pellets, bilayer, floating, and mucoadhesive tablets, as well as parenteral, transdermal, and rectal preparations. It also anticipates further possibilities in the development of PPIs dosage forms. It is especially addressed to the researchers developing new formulations containing PPIs, since it covers the most important formulary issues that need to be considered before a decision on the selection of the formula is made. It may help in avoiding unnecessary efforts in this process and choosing the best approach. The review also presents an up-to-date database of publications focused on the pharmaceutical technology of formulations with PPIs. [ABSTRACT FROM AUTHOR]

Pharmaceutical opioid dosage forms are commonly misused via an oral route in non-manipulated form, i.e., overdose in intact form, or manipulated form, i.e., after crushing the dosage form, and also via the non-oral route in manipulated form, particularly the parenteral or nasal route. To assess the self-regulated anti-overdose property, crushing strength, extractability, and syringeability of the developed drug delivery system by in vitro laboratory studies. Tapentadol HCl drug particulates fabricated using different polymers were assessed for extractability studies in 25 ml of water at room temperature (RT) and at > 90°C. Crushing strength was assessed by grinding the drug particulates in a mortar and pestle and a coffee grinder for 1 min. For syringeability, an attempt was made to withdraw the drug mixture using a 1 ml insulin syringe for 1 min. To assess the self-regulated anti-overdose property, in vitro dissolution testing on a single-capsule per dissolution vessel (normal condition) and four-capsules per dissolution vessel (overdose condition) was performed. POLYOX, Natrosol, and Blanose-containing drug particles retarded drug extraction by > 80% at RT and > 90°C. After 1 min of grinding in a mortar and pestle and a coffee grinder, crushed POLYOX-containing drug particulates were retained at > 99% on the ASTM-170# screen. The attempt to withdraw the viscous mixture of drug formulation prepared with 5 ml of water for 1 min using a 1 ml insulin syringe was unsuccessful. In dissolution studies, more than 90% of the drug was released in normal conditions, and more than 90% of the drug was retarded in overdose conditions. In vitro laboratory studies demonstrate that the developed self-regulated anti-overdose crush-resistant drug delivery system may deter misuse via oral and non-oral routes. [ABSTRACT FROM AUTHOR]

Armin Mooranian,1,2 Thomas Foster,1,2 Corina M Ionescu,1,2 Louise Carey,1,2 Daniel Walker,1,2 Melissa Jones,1,2 Susbin Raj Wagle,1,2 Bozica Kovacevic,1,2 Jacqueline Chester,1,2 Edan Johnstone,1,2 Jafri Kuthubutheen,3 Daniel Brown,4 Marcus D Atlas,2 Momir Mikov,5 Hani Al-Salami1,2 1The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, 6102, WA, Australia; 2Hearing Therapeutics, Ear Science Institute Australia, Queen Elizabeth II Medical Centre, Nedlands, Perth, 6009, WA, Australia; 3Fiona Stanley Hospital, Perth, WA, Australia; 4Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia; 5Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, 21101, SerbiaCorrespondence: Hani Al-SalamiHearing Therapeutics, Biotechnology and Pharmaceutical Sciences, Curtin University, Bentley, Perth, 6102, WA, AustraliaTel +61 8 9266 9816Fax + 61 8 9266 2769Email hani.al-salami@curtin.edu.auIntroduction: In a recent study, in our laboratory, primary unconjugated bile acids, commonly found in humans, chenodeoxycholic acid (CDCA), have been shown to improve stability of nanoencapsulated lipophilic drugs and improve their release profile after oral administration likely via electrokinetic stabilisation. Hence, this study aimed to examine the effects of CDCA on exerting similar effects on hydrophilic drugs.Methods: Various CDCA-based formulations were produced for the orally administered hydrophilic drug, metformin. Analyses of these formulations included electrokinetic potentials, topography, drug and CDCA formulation contents, nano size distribution, heat-induced deformation and outer-core expansion indices, release profiles, shell-resistance ratio, and thermal and chemical indices. With the drug’s main target being pancreatic beta-cells, the formulations’ effects on cell viability, functions and inflammatory profiles were also investigated.Results and Conclusions: CDCA-based metformin formulations exhibited improved stability and release profiles via thermal, chemical and electrokinetic effects, which were formulation-dependent suggesting potential applications of CDCA in the oral targeted delivery of hydrophilic drugs.Keywords: microencapsulation, diabetes mellitus, Glyceryl monooleate, Eudragit, chenodeoxycholic acid

Biodegradable polymeric nanocapsules (NC) present incredible characteristics as drug nanocarriers that optimize drug targeting. However, However, a more detailed isolated effect of polymer-based nanoparticles as drug carriers is required. This work aimed to evaluate the per se effect of blank-NC (NC-B) with different surface characteristics both in vitro and in vivo toxicity. NC1-B (Polysorbate 80 coated poly(ɛ-caprolactone) NC), NC2-B (polyethylene glycol 6000 coated poly(ɛ-caprolactone) NC), NC3-B (chitosan-coated poly(ɛ-caprolactone) NC) and NC4-B (Eudragit® RS100 NC) were prepared by nanoprecipitation method. Formulations were characterized by particle size, zeta potential, and pH. The in vitro cytotoxicity tests against tumor cell lines were performed (HepG2 and MCF-7). Antiviral activity was evaluated by MTT in Vero cells infected with HSV-1 (KOS strain). In vivo evaluation was performed in apomorphine-induced stereotypy in Wistar rats and locomotor activity distance, head movements, and rearing behavior were measured. NC1-B, NC2-B, NC3-B, and NC4-B had a diameter under 350 nm. The pH and zeta potential of formulations varied according to their coating. For in vitro evaluation of antitumor activity and antiviral activity, one-way ANOVA showed no significant differences in cell viability. In vivo tests showed low neurological effects. In conclusion, different surface characteristics of NC-B did not demonstrate toxicity against the evaluated cell lines HepG2 and MCF-7, antiviral effect against HSV-1, and the neurological effects in a stereotyping model were low and may be attributed to the per se effect of NC-B.

In this work, we report the use of the hot melt extrusion method in harsh extrusion conditions, i.e., screw rotation speed of 250 rpm, temperature above 100 °C, and two mixing zones, in order to obtain an amorphous dispersion of an active pharmaceutical ingredient (API) that is sparingly soluble in water. As a polymer matrix Eudragit EPO (E-EPO) and as an API ibuprofen (IBU) were used in the research. In addition, the plasticizer Compritol 888 ATO (COM) was tested as a factor potentially improving processing parameters and modifying the IBU release profile. In studies, 25% by weight of IBU, 10% of COM and various extrusion temperatures, i.e., 90, 100, 120, 130, and 140 °C, were used. Hot melt extrusion (HME) temperatures were selected based on the glass transition temperature of the polymer matrix (Tg = 42 °C) and the melting points of IBU (Tm = 76 °C) and COM (Tm = 73 °C), which were tested by differential scanning calorimetry (DSC). The thermal stability of the tested compounds, determined on the basis of measurements carried out by thermogravimetric analysis (TGA), was also taken into account. HME resulted in amorphous E-EPO/IBU solid dispersions and solid dispersions containing a partially crystalline plasticizer in the case of E-EPO/IBU/COM extrudates. Interactions between the components of the extrudate were also studied using infrared spectroscopy (FTIR-ATR). The occurrence of such interactions in the studied system, which improve the stability of the obtained solid polymer dispersions, was confirmed. On the basis of DSC thermograms and XRPD diffractograms, it was found that amorphous solid dispersions were obtained. In addition, their stability was confirmed in accelerated conditions (40 °C, 75% RH) for 28 days and 3 months. The release profiles of prepared tablets showed the release of 40% to 63% of IBU from the tablets within 180 min in artificial gastric juice solution, with the best results obtained for tablets with E-EPO/IBU extrudate prepared at a processing temperature of 140 °C.

Eluxadoline (ELD), a recently approved drug, exhibits potential therapeutic effects in the management and treatment of IBS-D. However, its applications have been limited due to poor aqueous solubility, leading to a low dissolution rate and oral bioavailability. The current study’s goals are to prepare ELD-loaded eudragit (EG) nanoparticles (ENPs) and to investigate the anti-diarrheal activity on rats. The prepared ELD-loaded EG-NPs (ENP1-ENP14) were optimized with the help of Box–Behnken Design Expert software. The developed formulation (ENP2) was optimized based on the particle size (286 ± 3.67 nm), PDI (0.263 ± 0.01), and zeta potential (31.8 ± 3.18 mV). The optimized formulation (ENP2) exhibited a sustained release behavior with maximum drug release and followed the Higuchi model. The chronic restraint stress (CRS) was successfully used to develop the IBS-D rat model, which led to increased defecation frequency. The in vivo studies revealed a significant reduction in defecation frequency and disease activity index by ENP2 compared with pure ELD. Thus, the results demonstrated that the developed eudragit-based polymeric nanoparticles can act as a potential approach for the effective delivery of eluxadoline through oral administration for irritable bowel syndrome diarrhea treatment.

The nano-drug delivery system has gained greater acceptability for poorly soluble drugs. Alogliptin (ALG) is a FDA-approved oral anti-hyperglycemic drug that inhibits dipeptidyl peptidase-4. The present study is designed to prepare polymeric ALG nanoparticles (NPs) for the management of diabetes. ALG-NPs were prepared using the nanoprecipitation method and further optimized by Box–Behnken experimental design (BBD). The formulation was optimized by varying the independent variables Eudragit RSPO (A), Tween 20 (B), and sonication time (C), and the effects on the hydrodynamic diameter (Y1) and entrapment efficiency (Y2) were evaluated. The optimized ALG-NPs were further evaluated for in vitro release, intestinal permeation, and pharmacokinetic and anti-diabetic activity. The prepared ALG-NPs show a hydrodynamic diameter of between 272.34 nm and 482.87 nm, and an entrapment efficiency of between 64.43 and 95.21%. The in vitro release data of ALG-NPs reveals a prolonged release pattern (84.52 ± 4.1%) in 24 h. The permeation study results show a 2.35-fold higher permeation flux than pure ALG. ALG-NPs exhibit a significantly (p < 0.05) higher pharmacokinetic profile than pure ALG. They also significantly (p < 0.05) reduce the blood sugar levels as compared to pure ALG. The findings of the study support the application of ALG-entrapped Eudragit RSPO nanoparticles as an alternative carrier for the improvement of therapeutic activity. [ABSTRACT FROM AUTHOR]

Oral administration of pH sensitive/stimuli responsive nanoparticles are gaining importance because of the limited side effects, minimum dose and controlled drug release. The objective of this study was to develop and evaluate pH sensitive polymeric nanoparticles for methotrexate with the aim to maximize the drug release at target site. In the presented study, pH sensitive polymeric nanoparticles of methotrexate were developed through modified solvent evaporation technique using polymer Eudragit S100. Different process parameters like drug to polymer ratio, speed of sonication, concentration of surfactant and time of sonication were optimized by evaluating their effects on particle size, PDI, zeta potential, entrapment/encapsulation efficiency. The developed formulations were evaluated for their size, polydispersity (PDI), zeta potential, encapsulation efficiency, XRD, scanning electron microscopy, in-vitro drug release and stability studies. Best results were obtained with poloxamer-407 and PVA and were selected as surfactants. Physicochemical characterization of the developed formulations showed that the particle size lies in the range 165.7 ± 1.85–330.4 ± 4.19, PDI 0.119 ± 0.02–0.235 ± 0.008, zeta potential −0.163 ± 0.11–−5.64 ± 0.36 mV, and encapsulation efficiency more than 61%. The results of scanning electron microscopy revealed that nanoparticles have regular geometry with spherical shape. Initially the drug release occur through diffusion followed by erosion. The present studies showed that MTX-ES100 nanoparticles prepared during this study have the desired physicochemical properties, surface morphology and release characteristics used to target the desired organs. Oral administration of pH sensitive/stimuli responsive nanoparticles are gaining importance because of the limited side effects, minimum dose and controlled drug release. The objective of this study was to develop and evaluate pH sensitive polymeric nanoparticles for methotrexate with the aim to maximize the drug release at target site. In the presented study, pH sensitive polymeric nanoparticles of methotrexate were developed through modified solvent evaporation technique using polymer Eudragit S100. Different process parameters like drug to polymer ratio, speed of sonication, concentration of surfactant and time of sonication were optimized by evaluating their effects on particle size, PDI, zeta potential, entrapment/encapsulation efficiency. The developed formulations were evaluated for their size, polydispersity (PDI), zeta potential, encapsulation efficiency, XRD, scanning electron microscopy, in-vitro drug release and stability studies. Best results were obtained with poloxamer-407 and PVA and were selected as surfactants. Physicochemical characterization of the developed formulations showed that the particle size lies in the range 165.7 ± 1.85–330.4 ± 4.19, PDI 0.119 ± 0.02–0.235 ± 0.008, zeta potential −0.163 ± 0.11–−5.64 ± 0.36 mV, and encapsulation efficiency more than 61%. The results of scanning electron microscopy revealed that nanoparticles have regular geometry with spherical shape. Initially the drug release occur through diffusion followed by erosion. The present studies showed that MTX-ES100 nanoparticles prepared during this study have the desired physicochemical properties, surface morphology and release characteristics used to target the desired organs. [ABSTRACT FROM AUTHOR]

Background: Circadian rhythms is a natural process that regulates the sleep wake cycle which is associated with several physiological, biochemical, endocrine, behavioural processes in humans and entrainment to light-dark cycle. The activity of Ramelteon is believed to contribute to its sleep-promoting properties and thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle. A tablet can be given before 2 hr of bed time, so the Ramelteon drug shows its effect throughout the night by releasing the active content with lag time followed by sustained action to promote the sleep. Materials and Methods: Chronotherapeutic drug delivery system were prepared by compression coating technology using pH independent, hydrophilic and hydrophobic polymers. Results: Drug excipient compatibility indicated that the Ramelteon Active pharmaceutical ingredient (API) is compatibility with the excipients proposed. The X-ray Diffraction (XRD) studies indicated that the crystalline form of the Ramelteon API existed in the finished formulation. Conclusion: The core tablets containing Eudragit RSPO 10mg/tablet and ratio of Ethyl cellulose: Hydroxy propyl methyl cellulose (HPMC) of 70:30 in the outer coating material yielded a desired lag time of 2 hr and drug release for a period of 4 hr to achieve a chronotherapeutic drug delivery system. Ramelteon is an excellent candidate in designing chronotherapeutic drug delivery systems and further in vivo studies can be explored in the treatment of circadian rhythm with sleep wake cycle disorders. [ABSTRACT FROM AUTHOR]