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الملخص: أهداف البحث: المضادات الحيوية هي الأدوية الأكثر شيوعا بين المرضى الأطفال. ومع ذلك، في معظم الأحيان، يصبح إعطاء الجرعة الدقيقة للأطفال مشكلة بسبب مذاقه المر للغاية. يعد سيفبودوكسيم بروكسيتيل وروكسيثروميسين أحد المضادات الحيوية التي توصف غالبا للأطفال ولها طعم مرير. التركيبات المسوقة لهذه الأدوية هي معلق جاف و/أو أقراص. من المعروف أن طريقة التجفيد تتضمن خطوات مختلفة وبالتالي فهي تستغرق وقتا طويلا ومكلفة. كان الهدف من هذه الدراسة هو إخفاء الطعم المر لسيفبودوكسيم بروكسيتيل وروكسيثروميسين دون المساس بالذوبان وشكل إطلاق الدواء عند مقارنته بالتركيبات المسوقة. بالإضافة إلى التغلب على العيوب المرتبطة بتقنية التجفيد المستخدمة حاليا. طريقة البحث: تم استخدام تقنية البثق بالذوبان الساخن لمعالجة سيفبودوكسيم بروكسيتيل وروكسيثروميسين بشكل فردي باستخدام بوليمر يودراجيت إيبو. تم تشخيص البثقات التي تم الحصول عليها بواسطة التحليل الطيفي للأشعة تحت الحمراء لتحويل فورييه، وقياس نمط الحيود للمواد البلورية وقياس السعرات الحرارية بالمسح التفاضلي. تمت صياغة البثقات المسحوقة كأقراص قابلة للتشتت وتم تقييمها من حيث كفاءة إخفاء الطعم داخل المختبر وفي الجسم الحي. النتائج: أظهرت الأقراص المحضرة في هذه الدراسة ملامح ذوبان قابلة للمقارنة ولكن تم تعزيز كفاءة إخفاء الطعم بشكل كبير عند مقارنتها بالأقراص المسوقة من سيفبودوكسيم بروكسيل وروكسيثروميسين. وكانت نتائج تقييم إخفاء الطعم البشري داخل الجسم متفقة أيضا مع دراسات إخفاء التذوق داخل المختبر. الاستنتاجات: وبالتالي فإن العمل الحالي قد قدم تكنولوجيا البثق بالذوبان الساخن الخالية من المذيبات والقابلة للتطوير والمستمرة لمعالجة مشكلات الطعم المر في سيفبودوكسيم بروكسيتيل وروكسيثروميسين. علاوة على ذلك، تم التغلب على العيوب المرتبطة بتقنية التجفيد المستخدمة حاليًا من خلال تطوير التركيبات باستخدام تقنية البثق بالذوبان الساخن. Abstract: Objectives: Antibiotics are the most commonly administered medications among pediatric patients. However most of the time, accurate dose administration to children becomes a problem due to the extremely bitter taste. Cefpodoxime proxetil (CP) and roxithromycin (ROX) are antibiotics often prescribed to the pediatric population and have a bitter taste. Marketed formulations of these drugs are dry suspension and/or tablets. The lyophilization method involves various steps and thus is time consuming and expensive. The objective of this study was to mask the bitter taste of CP and ROX without compromising the solubility and drug release profile compared to marketed formulations, as well as to overcome the disadvantages associated with the currently used lyophilization technique. Methods: Hot melt extrusion (HME) technology was used to process CP and ROX individually with Eudragit E PO polymer. The extrudates obtained were characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry. The powdered extrudates were formulated as dispersible tablets and evaluated for in vitro and in vivo taste-masking efficiency. Results: The tablets prepared in this study showed comparable dissolution profiles but the taste-masking efficiency was significantly enhanced compared to the marketed tablets of CP and ROX. The results of in vivo human taste-masking evaluation were also in agreement with the in vitro taste-masking studies. Conclusion: The current work presents solvent-free, scalable, and continuous HME technology for addressing the bitter taste issues of CP and ROX. The disadvantages associated with the currently used lyophilization technique were overcome by developing the formulations using HME technology.

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The unpleasant extremely bitter taste of the orally administered broad-spectrum antibiotic azithromycin decreases patient compliance, especially in pediatrics. This issue can be overcome by decreasing drug interaction with the tasting buds using insoluble polymers at salivary pH (6.8 − 7.4), like the cationic polymer Eudragit EPO. Supercritical fluid technology is a green synthesis method for preparing pharmaceutical preparations that replace organic solvents with safe supercritical CO2. This study aimed to mask the bitter taste of azithromycin using the supercritical fluid method and a pH-sensitive Eudragit EPO polymer. A foaming process was investigated for preparing a formulation (TEST), which comprises treating the polymer with supercritical carbon dioxide (CO2) fluid to prepare a taste-masked dosage form without employing organic solvents or flavors. The use of the supercritical technique at 40 °C and 10 MPa for 2 h allowed the manufacturing of solvent-free polymeric foam with azithromycin dispersions; the average calculated percentage of apparent volume change was 62.5 ± 5.9% with an average pore diameter of 34.879 Å. The formulated sample showed low drug release in simulated salivary fluid while keeping its crystalline nature. Moreover, clinical studies on healthy subjects showed that the formula successfully masked azithromycin's bitter taste. Overall, it has been shown herein that the supercritical fluid technology foaming method is promising in masking the bitter taste of bitter ingredients. [ABSTRACT FROM AUTHOR]

Flucloxacillin is prescribed to treat skin infections but its highly bitter taste is poorly tolerated in children. This work describes the application of the D-optimal mixture experimental design to identify the optimal component ratio of flucloxacillin, Eudragit EPO and palmitic acid to prepare flucloxacillin taste-masked microparticles that would be stable to storage and would inhibit flucloxacillin release in the oral cavity while facilitating the total release of the flucloxacillin load in the lower gastrointestinal tract (GIT). The model predicted ratio was found to be very close to the stoichiometric equimolar component ratio, which supported our hypothesis that the ionic interactions among flucloxacillin, Eudragit EPO and palmitic acid underscore the polyelectrolyte complex formation in the flucloxacillin taste-masked microparticles. The excipient–drug interactions showed protective effects on the microparticle storage stability and minimised flucloxacillin release at 2 min in dissolution medium. These interactions had less influence on flucloxacillin release in the dissolution medium at 60 min. Storage temperature and relative humidity significantly affected the chemical stability of the microparticles. At the preferred storage conditions of ambient temperature under reduced RH of 23%, over 90% of the baseline drug load was retained in the microparticles at 12 months of storage. [ABSTRACT FROM AUTHOR]

It is extremely challenging to formulate age-appropriate flucloxacillin medicines for young children, because flucloxacillin sodium (FS) has a lingering, highly bitter taste, dissolves quickly in saliva, and requires multiple daily dosing at relatively large doses for treating skin infections. In this paper, we describe a promising taste-masked flucloxacillin ternary microparticle (FTM) formulation comprising FS, Eudragit EPO (EE), and palmitic acid (PA). To preserve the stability of the thermolabile and readily hydrolysed flucloxacillin, the fabrication process employed a non-aqueous solvent evaporation method at ambient temperature. Optimisation of the fabrication method using a mixture design approach resulted in a robust technique that generated stable and reproducible FTM products. The optimised method utilised only a single solvent evaporation step and minimal amounts of ICH class III solvents. It involved mixing two solution phases—FS dissolved in ethanol:acetone (1:4 v/v), and a combination of EE and PA dissolved in 100% ethanol—to give a ternary FS:EE:PA system in ethanol: acetone (3:1 v/v). Solvent evaporation yielded the FTMs containing an equimolar ratio of FS:EE:PA (1:0.8:0.6 w/w). The fabrication process, after optimisation, demonstrated robustness, reproducibility, and potential scalability. [ABSTRACT FROM AUTHOR]

The objective of present study was to formulate and develop once daily Fexofenadine Hydrochloride tablets to improve the aqueous solubility by microsponge technology. Fexofenadine Hydrochloride is an antihistamine and belongs to BCS class-III with low permeability and poor bioavailability about 30 - 35 %. The microsponges were prepared by Quashi emulsion solvent diffusion method with Quality by design approach. The study of effect of independent variables Eudragit EPO (500 to 1,000 mg), internal phase volume (DM: ETH) (5 to 10 mL) and RPM (500 to 1,000) on responses were analyzed to optimize the formulation with desirable results by using central composite design and response surface method. Optimized formulation F22 showed percent production yield (99.10 %), percent drug entrapment (99.45 %), particle size (94.12 µm) and percent drug release of prepared tablets at 5, 10, 15 and 30 min were 60.6, 80.75, 87.47 and 92.85 %, respectively. It showed Higuchi mechanism of release kinetics by diffusion. In vivo pharmacokinetics of the prepared tablets was studied in rabbits (IAEC/NRML/2022--2023/09) with and without permeation enhancer to find the rate of absorption. when compared to Marketed product-Allegra 24 (F21) with (t1/2 absorption) 0.192711±0.00278 h and MRT 19.10608±0.257571 h and formulation without poloxamer 407 (F22) (t1/2 absorption) 0.165013±0.024164 h and MRT 19.32228±0.764531 h, maximum absorption was observed for the Formulation F23 with poloxamer 407 (15 %) with (t1/2 absorption) of 0.144662±0.006787 h and Mean residence time (MRT) of 24.10796±1.01232 h. Microsponge technique improved the aqueous solubility of the fexofenadine Hydrochloride and Eudragit EPO extended the mean residence time up to 24 h along with improved permeability in presence of Poloxamer 407 to full fill the needs of BCS class-III drug. [ABSTRACT FROM AUTHOR]

It is extremely challenging to formulate age-appropriate flucloxacillin medicines for young children, because flucloxacillin sodium (FS) has a lingering, highly bitter taste, dissolves quickly in saliva, and requires multiple daily dosing at relatively large doses for treating skin infections. In this paper, we describe a promising taste-masked flucloxacillin ternary microparticle (FTM) formulation comprising FS, Eudragit EPO (EE), and palmitic acid (PA). To preserve the stability of the thermolabile and readily hydrolysed flucloxacillin, the fabrication process employed a non-aqueous solvent evaporation method at ambient temperature. Optimisation of the fabrication method using a mixture design approach resulted in a robust technique that generated stable and reproducible FTM products. The optimised method utilised only a single solvent evaporation step and minimal amounts of ICH class III solvents. It involved mixing two solution phases—FS dissolved in ethanol:acetone (1:4 v/v), and a combination of EE and PA dissolved in 100% ethanol—to give a ternary FS:EE:PA system in ethanol: acetone (3:1 v/v). Solvent evaporation yielded the FTMs containing an equimolar ratio of FS:EE:PA (1:0.8:0.6 w/w). The fabrication process, after optimisation, demonstrated robustness, reproducibility, and potential scalability.

Flucloxacillin is prescribed to treat skin infections but its highly bitter taste is poorly tolerated in children. This work describes the application of the D-optimal mixture experimental design to identify the optimal component ratio of flucloxacillin, Eudragit EPO and palmitic acid to prepare flucloxacillin taste-masked microparticles that would be stable to storage and would inhibit flucloxacillin release in the oral cavity while facilitating the total release of the flucloxacillin load in the lower gastrointestinal tract (GIT). The model predicted ratio was found to be very close to the stoichiometric equimolar component ratio, which supported our hypothesis that the ionic interactions among flucloxacillin, Eudragit EPO and palmitic acid underscore the polyelectrolyte complex formation in the flucloxacillin taste-masked microparticles. The excipient–drug interactions showed protective effects on the microparticle storage stability and minimised flucloxacillin release at 2 min in dissolution medium. These interactions had less influence on flucloxacillin release in the dissolution medium at 60 min. Storage temperature and relative humidity significantly affected the chemical stability of the microparticles. At the preferred storage conditions of ambient temperature under reduced RH of 23%, over 90% of the baseline drug load was retained in the microparticles at 12 months of storage.

The aim of this study was to investigate the influence of the production method and the polymeric carrier on the ability to generate and maintain the supersaturation of a poorly soluble drug in biorelevant medium. The amorphous solid dispersion of sulfamethoxazole, an antibacterial drug, was produced using two different polymers by spray-drying or hot melt extrusion methods. When Eudragit EPO was used, supersaturation was maintained up to 24 h for both techniques at all drug-polymer proportions. However, when Soluplus was employed in hot melt extrusion, a smaller amount of drug was dissolved when compared to the amorphous drug. The proportion of 3:7 drug-Eudragit EPO (w/w) produced by spray-drying presented a higher amount of drug dissolved in supersaturation studies and it was able to maintain the physical stability under different storage conditions throughout the 90-day evaluation. Supersaturation generation and system stability were found to be related to more effective chemical interaction between the polymer and the drug provided by the production method, as revealed by the 1D ROESY NMR experiment. Investigation of drug-polymer interaction is critical in supersaturating drug delivery systems to avoid crystallization of the drug and to predict the effectiveness of the system. Chemical compounds studied in this article: Sulfamethoxazole (PubChem CID: 4539) and Methacrylate copolymer — Eudragit EPO (PubChem CID: 65358) [ABSTRACT FROM AUTHOR]

Tadalafil (TDL) a BCS-II drug is recently reported for repurposing nephroprotective effect in Pyelonephritis (PN). However, poor water solubility and dissolution rate limited oral bioavailability pose serious challenges in its therapeutic applications. We present an advanced third generation Solid Dispersion (SD) of TDL comprising a polymer in combination with a Self Micro-emulsifying Composition (SMEC) to achieve high drug loading, improved stability and rapid dissolution of TDL for enhancing bioavailability and efficacy in PN. TDL-SMEC-SD was coated onto rapidly disintegrating inert tablet cores which disintegrated rapidly in water to release SD as a film. TDL-SMEC-SD was evaluated for in-vivo oral bioavailability and in-vivo efficacy in lipopolysaccharide-induced PN in rats. TDL exhibited high solubility (45.6 mg/ml) in the SMEC. TDL-SMEC-SD exhibited remarkably high TDL loading (45%w/w), exceptionally low contact angle (9°), rapid in-vitro release (t50 7.3 min), microemulsion formation (globule size ~100 nm) in aqueous dispersion, and stability as per ICH guidelines. SEM, DSC, and XRD confirmed high physical stability. A relative bioavailability of 350% and 150% compared to TDL and TDL-SD without SMEC respectively, established the superiority of TDL-SMEC-SD. A significant reduction in serum creatinine, blood urea nitrogen and nitric oxide levels in the lipopolysaccharide-induced PN confirmed the benefit of the TDL-SMEC-SD. The advanced third generation SMEC SDs presents the possibility of platform technology for bioenhancement of poorly water soluble drugs.

Background: The drug supersaturation in the intestinal lumen for few hours could result in high bioavailability. The goal of this study was the development of a supersaturating drug delivery system containing sulfamethoxazole and trimethoprim at fixed dose combination (sulfamethoxazole:trimethoprim 5:1 w/w). Methods: The amorphous solid dispersions were formed at three different proportions containing 30, 50 and 70% of Eudragit EPO in the formulation. Results: The supersaturation state is formed by the amorphous drugs produced by spray drying technique, and the maintenance of this state is due to the chemical interactions between the drugs and the polymer selected, which was observed in the fluorescence interaction studies realized between the drugs and the polymer. The Formulation containing 70% of the polymer was able to produce and maintain the supersaturated state of both drugs for 24 h. Solid state characterization demonstrated the amorphization of the drugs in the solid dispersion and indicated the hydrogen bond formation responsible for the improvement in the apparent solubility. This formulation presented an improved antibacterial activity when compared to the combination of the drugs. Conclusion: For the first time, a supersaturating drug delivery system was developed to the complementary antibacterial drugs. This ternary formulation is a powerful alternative to improve oral absorption of recognized safety drugs, reducing the dose and consequently the antibiotic resistance emergence. [ABSTRACT FROM AUTHOR]

Objectives: Polymeric nanoparticles are a promising novel drug delivery system and have advantages in cancer therapy. Etoposide is an anticancer agent that is used in the treatment of a variety of malignancies. The aim of the present study was to prepare and evaluate novel polymeric nanoparticles containing etoposide. Materials and Methods: A 3² full factorial design was used to study the effect of Eudragit EPO and Pluronic F-68 on the characterization of nanoparticle suspensions. The polymeric nanoparticles were prepared by nanoprecipitation technique. The prepared nanoparticles was evaluated by percentage yield, drug polymer compatibility using fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetric (DSC) analysis, drug content, entrapment efficiency, zeta potential, particle size, scanning electron microscopy, X-ray diffraction, in vitro drug release studies, kinetic modeling, stability studies, and in vivo animal studies. Response surface plots were studied, which were generated using PCP dissolution software. Results: Scanning electron microscopic studies confirmed their porous structure with a number of nanochannels. The FTIR spectra showed the stable character of etoposide in a mixture of polymers and revealed the absence of drug-polymer interactions. The DSC study revealed that the drug was involved in complexation with nanoparticles. The average particle size of etoposide nanoparticles was in the range of 114.4 nm to 136.7 nm. The zeta potential values were attained to ensure good stability of nanosuspensions. In vitro release of the drug from nanoparticles follows the Peppas model and showed controlled release behavior for a period of 24 h. The optimized nanoparticles were subjected to stability studies at 4°C in a refrigerator and the most suitable temperature for storage of etoposide nanoparticles found. The average targeting efficiency of drugloaded nanoparticles was 41.88±0.030% of the injected dose in the liver, 25.66±0.320% in the spleen 13.82±0.090% in the lungs, 4.52±0.300% in the kidney, and 4.18±0.490% in the brain. Conclusion: Etoposide loaded nanoparticles was found to be effective in sustained release. [ABSTRACT FROM AUTHOR]

Objectives: Antibiotics are the most commonly administered medications among pediatric patients. However most of the time, accurate dose administration to children becomes a problem due to the extremely bitter taste. Cefpodoxime proxetil (CP) and roxithromycin (ROX) are antibiotics often prescribed to the pediatric population and have a bitter taste. Marketed formulations of these drugs are dry suspension and/or tablets. The lyophilization method involves various steps and thus is time consuming and expensive. The objective of this study was to mask the bitter taste of CP and ROX without compromising the solubility and drug release profile compared to marketed formulations, as well as to overcome the disadvantages associated with the currently used lyophilization technique., Methods: Hot melt extrusion (HME) technology was used to process CP and ROX individually with Eudragit E PO polymer. The extrudates obtained were characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry. The powdered extrudates were formulated as dispersible tablets and evaluated for in vitro and in vivo taste-masking efficiency., Results: The tablets prepared in this study showed comparable dissolution profiles but the taste-masking efficiency was significantly enhanced compared to the marketed tablets of CP and ROX. The results of in vivo human taste-masking evaluation were also in agreement with the in vitro taste-masking studies., Conclusion: The current work presents solvent-free, scalable, and continuous HME technology for addressing the bitter taste issues of CP and ROX. The disadvantages associated with the currently used lyophilization technique were overcome by developing the formulations using HME technology., (© 2023 The Authors.)

Tadalafil (TDL) a BCS-II drug is recently reported for repurposing nephroprotective effect in Pyelonephritis (PN). However, poor water solubility and dissolution rate limited oral bioavailability pose serious challenges in its therapeutic applications. We present an advanced third generation Solid Dispersion (SD) of TDL comprising a polymer in combination with a Self Micro-emulsifying Composition (SMEC) to achieve high drug loading, improved stability and rapid dissolution of TDL for enhancing bioavailability and efficacy in PN. TDLSMEC- SD was coated onto rapidly disintegrating inert tablet cores which disintegrated rapidly in water to release SD as a film. TDL-SMEC-SD was evaluated for in-vivo oral bioavailability and in-vivo efficacy in lipopolysaccharide-induced PN in rats. TDL exhibited high solubility (45.6 mg/ml) in the SMEC. TDL-SMEC-SD exhibited remarkably high TDL loading (45%w/w), exceptionally low contact angle (9°), rapid in-vitro release (t50 7.3 min), microemulsion formation (globule size ~100 nm) in aqueous dispersion, and stability as per ICH guidelines. SEM, DSC, and XRD confirmed high physical stability. A relative bioavailability of 350% and 150% compared to TDL and TDL-SD without SMEC respectively, established the superiority of TDL-SMEC-SD. A significant reduction in serum creatinine, blood urea nitrogen and nitric oxide levels in the lipopolysaccharide-induced PN confirmed the benefit of the TDL-SMECSD. The advanced third generation SMEC SDs presents the possibility of platform technology for bioenhancement of poorly water soluble drugs. [ABSTRACT FROM AUTHOR]

Sumatriptan succinate (SS) is a drug used in the treatment of migraine headaches, but suffers from low patient compliance due to its unpalatable bitter taste. The purpose of the present work was to prepare taste-masked oro dispersible tablets (ODTs) of SS by incorporating drug loaded microspheres into tablets for use in patients experiencing difficulty in swallowing. Microspheres loaded with SS were prepared by solvent evaporation technique. Eudragit EPO, a pH-sensitive aminoalkylmethacrylate copolymer, was used for coating the drug particles, acetone as solvent for the polymer and light liquid paraffin as an encapsulating medium. Drug : polymer ratio of 1:1 was considered to be optimized formulation with a yield of 99.96%, entrapment efficiency of 61.55%, particle size ranging from 30.32 – 90.96μm and in vitro drug release of 85.06% within an hour. FTIR studies suggested absence of drug-excipient interaction. Tablets prepared by direct compression containing microspheres and effervescent agents were evaluated for pre-compression and post-compression parameters. The wetting time, in vitro dispersion time and in vitro disintegration time of the tablets were found to be 39 sec, 35 sec and 32 sec, respectively. The drug release from the tablet was about 85.44% within an hour. The SEM of final ODTs revealed that the microspheres remained intact even after compression. Stability studies indicated that the selected formulation was stable. The results obtained suggested that effective taste-masking was achieved for SS using the technique of microencapsulation and ODTs of acceptable characteristics were obtained by adding effervescent agents followed by direct compression. [ABSTRACT FROM AUTHOR]

Oily liquid drugs are not convenient for oral administration. We developed a powder containing clofibrate (CF), a model of an oily drug, using aminoalkyl methacrylate copolymer (EPO) or methacrylic acid copolymer (L100). CF or a mixture of CF and soybean oil was emulsified with EPO or L100 aqueous solution. Using a high-pressure homogenizer, a stable emulsion was obtained, and a powder was then obtained by lyophilization of the emulsion. The content of CF in the powder depended on the formulation, with the highest contents being 24.6% and 27.1% for EPO and L100, respectively. The incorporation ratio of CF was higher for L100 than for EPO. The powder using EPO was sticky because of leaked CF and the low glass transition temperature of EPO. The powder using L100 was a typical powder obtained by lyophilization. The leakage of CF from the powder was <2%, lower than for EPO powder. The dissolution of CF from powder using EPO was fast, regardless of the pH of the medium, but the powder using L100 showed enteric-soluble characteristics, indicating that CF is well incorporated in L100. [ABSTRACT FROM AUTHOR]

Drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated as orally fast-disintegrating tablets (FDTs or ODTs). Therefore, taste masking of active ingredients becomes essential in these systems because the drug is entirely released in the mouth. Despite advances in the FDT technologies, formulation of drugs with a bitter taste is still a challenge, especially when the amount of drug is high. In this study, a new solution is being developed to incorporate higher doses of a model bitter taste drug; ketoprofen, without affecting the fast-disintegrating properties of the formulation. The unpleasant taste of the active drug usually masked by adding flavoring ingredients and sweeteners to improve taste and palatability but in this study a novel approach of using a polymer; Eudragit EPO and a granulation procedure of this polymer with the active drug was applied to mask the bitter taste of ketoprofen. In order to produce ketoprofen FDT formulations, a two-stepped procedure was followed; granulation process with the taste-masking agent (Eudragit EPO) and then direct compression (F3 and F4). In F1 and F2 formulations, granulation process was not implemented in order to observe the effect of application method of Eudragit EPO. As well as observing the effect of taste-masking agent,crospovidoneandsodium starch glycolatewere used in different concentrations (2, 4 and 8wt%) to examine the influence of superdisintegrants on FDT properties. All the FDTs containing 30 mg ketoprofen (F1, F2, F3 and F4) were evaluated by means ofin vitroquality control tests. [ABSTRACT FROM PUBLISHER]

The aim of the study is to develop a floating microsponges of allopurinol to minimize the frequency of dosing by increasing half life and sustained release action up to 12 hrs by single unit dosage form. Allopurinol is xanthine oxidase inhibitor drug that leads to decrease in the production of uric acid from xanthine and hypoxanthine. It is BCS class I drug. It shows absorption window in upper gastro intestinal track, which makes it suitable candidate for gastro retentive dosage forms. Floating microsponges of allopurinol was formulated with quasi emulsion solvent diffusion method using Ethyl cellulose and Eudragit EPO as a polymer. A 3² factorial design was applied to optimize the formulation, it was found that formulation containing Ethyl cellulose 175 mg and of Eudragit EPO 75 mg, % drug release of allopurinol in 12 hrs with desired % buoyancy and % entrapment and best formulation was selected. The final optimized formulation shows entrapment 90.61%, buoyancy 86.52% and in vitro drug release 94.23% up to 12 hrs. Particle size was measured by optical microscopy. By using FTIR analysis drug and polymer compatibility was observed and using SEM prepared microsponges shape and surface morphology was determined. Accelerated stability study was carried for a period of 1 month. It was found that there was no significant change in formulation. [ABSTRACT FROM AUTHOR]

Context: Serious efforts have been made to overcome the bioavailability problems of ever increasing number of poorly soluble drugs, including atorvastatin (ATO); however, enhancing its gastric solubility has not received much attention. Objectives: To improve the bioavailability of ATO by increasing its gastric solubility in a stable oral disintegration tablet (ODT) formulation. Materials and methods: Amorphous solid dispersion (ASD) of ATO with Eudragit® EPO was used as API in ODT formulation. Characterization using Differential scanning calorimetry, Powder X-ray diffraction, Fourier transform infrared drug-polymer interaction simulated by molecular modeling, solubility, dissolution and stability studies together with in vivo evaluation. Results and discussion: In ASD there was uniform distribution of drug in the polymer and it retained the amorphous nature without any chemical interactions except the possibility of hydrogen bond formation, with substantially higher gastric solubility. The dissolution profile of the ODT containing ASD was significantly improved >90% within 15 min compared with 25% of plain ATO formulation. In vivo results showed an overall enhancement in the apparent bioavailability (83% and 434% more than Lipitor® and plain amorphous ATO tablets, respectively). Combining the ASD with ODT presents a reliable solution to overcome the low solubility and bioavailability problems of ATO in a simple, robust and cost effective formulation. [ABSTRACT FROM AUTHOR]

We report here a comparative study of the release of model drug diclofenac sodium from samples of interpolyelectrolyte complexes (IPEC) in in vitro conditions on a rotating basket apparatus and in vivo in experiments in rabbits. The study IPEC were prepared using different grades of Carbopol polymer (C71g, C2020) and Noveon AA-1 and oppositely charged polyelectrolytes - Eudragit EPO or the natural polysaccharide low-viscosity chitosan. These studies demonstrated the potential for IPEC samples based on Carbopol as a new modified-release drug delivery system. At the same time, assessment of bioadhesive properties provided evidence of the potential for using IPEC based on C2020/EPO as a mucoadhesive carrier. [ABSTRACT FROM AUTHOR]

Highlights: [•] High-speed and high-pressure homogenization was used to obtain nano-liposome. [•] Liposome was successfully coated by chitosan and eudragit EPO. [•] Physicochemical properties of liposome were affected by manufacture condition. [•] Storage stability of liposomes was enhanced by the polymer coating. [Copyright &y& Elsevier]

Many drugs are abandoned due to poor aqueous solubility, although having a potential therapeutic effect. Numerous methods have been followed to improve the dissolution rate of poorly water soluble drugs. Solid dispersion is successfully applied to improve the solubility and consequently the bioavailability of poorly water soluble drugs. The aim of present study was to prepare solid dispersions of Pioglitazone HCl with PEG 6000, PVP, Poloxamer 407, Eudragit EPO and HPMC and determine the effect of those polymers on dissolution of pioglitazone HCl. solid dispersion of Pioglitazone HCl was prepared by solvent evaporation method. Solid dispersions were evaluated with respect to their yield percentage, percent drug content, FT-IR spectra and in vitro dissolution studies. The histogram response, descriptive statistics of response ensure the fitness of the experiment. The result obtained show that the dissolution profile of Pioglitazone HCl solid dispersion was considerably improved. Solid dispersions of Pioglitazone HCl with PVP K30, HPMC, PEG 6000, Eudragit EPO and Poloxamer 407 shows 75%, 74%, 100%, 50% and 62% release respectively after 30 minutes where as Pioglitazone HCl shows only 12.05%. Based on the result solid dispersion technique can be an acceptable method for improving the dissolution profile of poorly aqueous soluble drug. [ABSTRACT FROM AUTHOR]

New interpolyelectrolyte complexes (IPECs) between oppositely charged Eudragit EPO and Eudragit L100 were investigated with a view to the development of oral controlled drug delivery systems (DDS). Structural features of the samples were evaluated by modulated-temperature differential scanning calorimetry (MTDSC). The results confirmed that all IPECs were chemically homogeneous and were characterized by only one glass-transition temperature. Evaluation of the diffusion-transport properties of the investigated IPECs revealed the basic mechanisms responsible for the controlled delivery of drugs with different physicochemical properties. The results showed that the synthesized IPECs have great potential to be used as pH-sensitive oral controlled DDS. [ABSTRACT FROM AUTHOR]

Purpose: The stabilization mechanism of a supersaturated solution of mefenamic acid (MFA) from a solid dispersion with EUDRAGIT EPO (EPO) was investigated. Methods: The solid dispersions were prepared by cryogenic grinding method. Powder X-ray diffractometry, in vitro dissolution test, in vivo oral absorption study, infrared spectroscopy, and solid- and solution-state NMR spectroscopies were used to characterize the solid dispersions. Results: Dissolution tests in acetate buffer (pH 5.5) revealed that solid dispersion showed > 200-fold higher concentration of MFA. Supersaturated solution was stable over 1 month and exhibited improved oral bioavailability of MFA in rats, with a 7.8-fold higher area under the plasma concentration- versus-time curve. Solid-state H spin-lattice relaxation time (T) measurement showed that MFA was almost monomolecularly dispersed in the EPO polymer matrix. Intermolecular interaction between MFA and EPO was indicated by solid-state infrared and C-T measurements. Solution-state H-NMR measurement demonstrated that MFA existed in monomolecular state in supersaturated solution. H-T and difference nuclear Overhauser effect measurements indicated that cross relaxation occurred between MFA and EPO due to the small distance between them. Conclusions: The formation and high stability of the supersaturated solution were attributable to the specifically formed intermolecular interactions between MFA and EPO. [ABSTRACT FROM AUTHOR]

Background: The purpose of the present work is to mask the intensely bitter taste of Itopride HCl and to formulate an Oro dispersible tablet (ODT) of the taste-masked drug by incorporation of microspheres in the tablets for use in specific populations viz. pediatrics, geriatrics and patients experiencing difficulty in swallowing. Methods: With this objective in mind, microspheres loaded with Itopride HCl were prepared by solvent evaporation method using acetone as solvent for pH-sensitive polymer, Eudragit EPO and light liquid paraffin as the encapsulating medium. The prepared microspheres were characterized with regard to yield, drug content, flow properties, particle size and size distribution, surface features, in vitro drug release and taste. The ODTs so prepared from these microspheres were evaluated for hardness, thickness, weight variation, friability, disintegration time, drug content, wetting time, water absorption ratio, moisture uptake, in vitro dispersion, in vitro disintegration, in vitro drug release and stability. Results: The average size of microspheres was found to be satisfactory in terms of the size and size distribution. Microspheres prepared were of a regular spherical shape. Comparison of the dissolution profiles of microspheres in different pH media showed that microspheres having drug: polymer ratio of 1:2 produced a retarding effect in simulated salivary fluid (pH 6.8) and were further used for formulation into ODTs after addition of suitable amounts of excipients such as superdisintegrant, diluent, sweetener and flavor of directly compressible grade. Conclusions: Effective taste-masking was achieved for Itopride HCl by way of preparation of microspheres and ODTs of acceptable characteristics. [ABSTRACT FROM AUTHOR]

New interpolyelectrolyte complexes (IPECs) between oppositely charged types of Eudragit EPO and Eudragit L100 were synthesized at pH 6.0, 6.5, and 7.0 with a view to their application in oral controlled drug delivery systems. Differences among the obtained IPECs were evaluated by FTIR spectroscopy and elemental analy- sis. The results confirm that the polycomplexes are stabilized by intermacromolecular ionic bonds and have compositions Z = 1.02, 1.49, and 2, respectively. Monitoring of microenvironmental changes in the polycomplex matrices during swelling in model gastrointestinal fluids indicates that all IPECs can be considered as potential pH-sensitive carriers due to structural and compositional transformations. The established properties of the synthesized IPECs suggest that they have high potential to be used as pH-dependent oral drug delivery systems. [ABSTRACT FROM AUTHOR]

Background: Chebulinic acid (CA), a component in Terminalia chebula , exhibits antiulcer activity, but has poor aqueous solubility. Raft-forming systems incorporating solid dispersions (SDs) of CA, were developed to overcome its poor biopharmaceutical properties and to prolong the gastric residence time for maximum activity. Methods: SDs were formulated by a solvent evaporation method using Eudragit EPO. Raft formulations consisted of sodium alginate as a polymer. Results: Release of CA in the dissolution medium was 40%, whereas SDs showed 95.45% release. The CA raft system (20 mg/kg) showed curative efficacy in an alcohol-induced gastric ulcer model and increased protection when compared with omeprazole (10 mg/kg) and CA suspension (20 mg/kg). Conclusion: These studies demonstrated SD raft systems to be a promising approach for antiulcer therapy by CA.

The formation of interpolyelectrolyte complexes (IPEC) between Eudragit EPO (EPO) and Carbomer 940 (C940) was investigated with a view to their use in peroral controlled-release drug delivery systems. The structure of the synthesized products was investigated using FTIR spectroscopy and MT-DSC methods, which indicated that the synthesized product can be considered to be an IPEC stabilized by a cooperative system of ionic bonds. Based on results of capillary viscosimetry and elemental analysis, the IPEC prepared at pH 4.0 has a characteristic composition with a C940:EPO mole ratio of 1.75:1. [ABSTRACT FROM AUTHOR]

The purpose of this work was to investigate the use of the dimethylaminoethyl methacrylate-copolymer Eudragit EPO (EPO) in oral solubility-enabling formulations for anionic lipophilic drugs, aiming to guide optional formulation design and maximize oral bioavailability. We have studied the solubility, the permeability, and their interplay, using the low-solubility nonsteroidal anti-inflammatory drug mefenamic acid as a model drug. Then, we studied the biorelevant solubility enhancement of mefenamic acid from EPO-based formulations throughout the gastrointestinal tract (GIT), using the pH-dilution dissolution method. EPO allowed a profound and linear solubility increase of mefenamic acid, from 10 μg/mL without EPO to 9.41 mg/mL in the presence of 7.5% EPO (∼940-fold; 37 °C); however, a concomitant decrease of the drug permeability was obtained, both in vitro and in vivo in rats, indicating a solubility-permeability trade-off. In the absence of an excipient, the unstirred water layer (UWL) adjacent to the GI membrane was found to hinder the permeability of the drug, accounting for this UWL effect and revealing that the true membrane permeability allowed good prediction of the solubility-permeability trade-off as a function of EPO level using a direct relationship between the increased solubility afforded by a given EPO level and the consequent decreased permeability. Biorelevant dissolution studies revealed that EPO levels of 0.05 and 0.1% were insufficient to dissolve mefenamic acid dose during the entire dissolution time course, whereas 0.5 and 1% EPO allowed complete solubility with no drug precipitation. In conclusion, EPO may serve as a potent solubility-enabling excipient for BCS class II/IV acidic drugs; however, it should be used carefully. It is prudent to use the minimal EPO amounts just sufficient to dissolve the drug dose throughout the GIT and not more than that. Excess amounts of EPO provide no solubility gain and cause further permeability loss, jeopardizing the overall success of the formulation. This work may help the formulator to hit the optimal solubility-permeability balance, maximizing the oral bioavailability afforded by the formulation.