New metabolites of the drug 5-aminosalicylic acid. I: N-β-D-glucopyranosyl-5-aminosalicylic acid

1. A new unstable metabolite of 5-aminosalicylic acid (5-ASA) was found in plasma from healthy volunteers dosed with 5-ASAi.v.

2. The metabolite was prepared by incubation of 5-ASA with rat liver homogenate, and isolated using preparative?h.p.l.c.

3. The metabolite was identified as N-β-D-glucopyranosyl-5-aminosalicylic acid by n.m.r. spectroscopy and by FAB mass spectrometry.

4. N-β-D-Glucopyranosyl-5-ASA was formed non-enzymically from 5-ASA and glucose in phosphate buffer pH7.4, and was unstable under weakly acidic conditions, decomposition increasing with temperature, i.e. decomposition was complete after 30?min at pH 5.0 and 23°C.     

Application of a Colon Delivery Capsule to 5-Aminosalicylic Acid and Evaluation of the Pharmacokinetic Profile after Oral Administration to Beagle Dogs

Abstract

Pressure-controlled colon delivery capsule (PCC) containing 5-aminosalicylic acid (5-ASA) for the treatment of inflammatory bowel disease (IBD) was prepared and evaluated by an in vivo experiment using beagle dogs. As a reference drug, sulfasalazine (SASP), prodrug of 5-ASA, was used as a plain gelatin capsule preparation. After the oral administration of SASP at the dose of 25.0 mg/kg, the mean time when the plasma 5-ASA concentration reaches to its maximum (Tmax) was 9.0 hr. In the case of 5-ASA administered in PCC, at the doses of 12.5 and 25.0 mg/kg, Tmaxs were 5.3 and 5.3 hr, respectively. Although the time for the first appearance of 5-ASA into the systemic circulation was almost the same value between SASP capsule and PCC containing 5-ASA, longer Tmax was observed from SASP capsule than from PCC. These results suggest that this 5-ASA preparation would be an useful dosage form for the therapy of IBD from the point of avoiding the side effect of sulfapyridine, one of the metabolites of SASP.     

Synthesis and properties of 5-aminosalicyl-taurine as a colonspecific prodrug of 5-aminosalicylic acid

5-Aminosalicylic acid (5-ASA) is an active ingredient of therapeutic agents used for Crohn's disease and ulcerative colitis. Because it is absorbed rapidly and extensively in the upper intestine, delivery of the agent specifically to the colon is necessary. We selected taurine as a colon-specific promoiety and designed 5-aminosalicyltaurine (5-ASA-Tau) as a new colon-specific prodrug of 5-aminosalicylic acid (5-ASA). It was expected that introduction of taurine would restrict the absorption of the prodrug and show additive effect to the anti-inflammatory action of 5-ASA after hydrolysis. 5-ASA-Tau was prepared in good yield by a simple synthetic route. The apparent partition coefficient of 5-ASA-Tau in 1-octanol/pH 6.8 phosphate buffer or CHCl3/pH 6.8 phosphate buffer was 0.10 or 0.18, respectively, at 37 degrees C. To determine the chemical and biochemical stability in the upper intestinal environment, 5-ASA-Tau was incubated in pH 1.2 and 6.8 buffer solutions, and with the homogenates of tissue and contents of stomach or small intestine of rats at 37 degrees C. 5-ASA was not detected from any of the incubation medium with no change in the concentration of 5-ASA-Tau. On incubation of 5-ASA-Tau with the cecal and colonic contents of rats, the fraction of the dose released as 5-ASA was 45% and 20%, respectively, in 8 h. Considering low partition coefficient and stability in the upper intestine, 5-ASA-Tau might be nonabsorbable and stable in the upper intestine. After oral administration, it would be delivered to the colon in intact form and release 5-ASA and taurine. These results suggested 5-ASA-Tau as a promising colon-specific prodrug of 5-ASA.     

Sustained release nanoparticulate formulation containing antioxidant-ellagic acid as potential prophylaxis system for oral administration

The aim of the present work was to develop ellagic acid (EA) loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for oral administration. PLGA nanoparticles were prepared by a method based on the concept of emulsion–diffusion–evaporation by using polyethylene glycol (PEG) 400 as a cosolvent for solubilizing the drug. While developing this method, didodecyldimethylammomium bromide (DMAB) and polyvinyl alcohol (PVA), alone and in combination with chitosan (CS) were employed. DMAB stabilized particles were the smallest of all the formulations with a particle size of 148.5 nm. PVA alone gave particles of 269.7 nm but a blend with CS (80:20) resulted in an increase in particle size (359.6 ± 23.6 nm). Initial release of EA from nanoparticles in pH 7.4 phosphate buffer was rapid, followed by a slower sustained release. Release rates followed the order PVA > PVA–CS > DMAB. Release rate from the PLGA–DMAB particles was slowest, which is attributed to higher hydrophobicity of DMAB as compared to PVA, preventing diffusion of drug out of polymeric matrix. Insolubility of CS at alkaline pH could have retarded the release in case of PVA–CS system. In situ intestinal permeability study of pure drug and the drug encapsulated in nanoparticles prepared using PVA, PVA–CS blend and DMAB as stabilizer in rats showed 66, 75, 73 and 87% permeation, respectively. EA showed good free radical scavenging effect in a yeast cell culture model as well as in a cell free system.     

滤膜吸附对复方甘草酸苷片溶出度的干扰试验

目的：考察滤膜对不同介质中复方甘草酸苷片溶出度的吸附情况,为其溶出试验的滤膜选择提供依据。方法：取复方甘草酸苷片,分别用水、pH 1.0盐酸、pH 4.5磷酸盐缓冲液、pH 6.8磷酸盐缓冲液4种介质,配制低、中、高3种浓度的供试品溶液,经不同滤膜过滤,用高效液相色谱法检测其溶出度并计算滤膜吸附率。结果：微孔滤膜对复方甘草酸苷片中甘草酸单铵盐吸附作用较大,在pH 1.0盐酸中吸附尤为明显;对甘氨酸、DL-蛋氨酸吸附作用较小;对低浓度供试品溶液的吸附作用大于高浓度供试品溶液。结论：滤膜吸附对4种介质中的溶出度测定有不同程度的干扰,在溶出试验前必须进行滤膜吸附试验,以选择合适的滤膜,排除干扰。     

Preparation of novel solid lipid microparticles loaded with gentamicin and its evaluation in vitro and in vivo

Objective: To formulate and evaluate solid-reversed-micellar-solution (SRMS)-based solid lipid microparticles (SLMs) for intramuscular administration of gentamicin.

Methods: SRMS formulated with Phospholipon® 90G and Softisan® 154 were used to prepare gentamicin-loaded SLMs. Characterizations based on size and morphology, stability and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release of gentamicin from the SLMs was performed in phosphate buffer while in vivo release studies were conducted in rats.

Results: Maximum EE% of 90.0, 91.6 and 83.0% were obtained for SLMs formed with SRMS 1:1, 1:2 and 2:1, respectively. Stable, spherical and smooth SLMs of size range 9.80?±?1.46?µm to 33.30?±?6.42?µm were produced. The release of gentamicin in phosphate buffer varied widely with the lipid contents. Moreover, significant (p?<?0.05) amount of gentamicin was released in vivo from the SLMs.

Conclusion: SRMS-based SLMs would likely offer a reliable means of delivering gentamicin intramuscularly.     

Microencapsulation with carrageenan-locust bean gum mixture in a multiphase emulsification technique for sustained drug release

Abstract

A multiphase emulsification technique was modified in this process of microencapsulating gentamicin sulphate, thus avoiding the necessity for a surfactant in preparing the secondary emulsion for a W/O/W emulsion. Various proportions of iota-carrageenan (i-C) and locust bean gum (LBG) were investigated for the W/O/W emulsion after forming the primary W/O emulsion with sorbitan trioleate, Span 85. Upon removal of the oil phase (chloroform) from the W/O/W emulsion by heating (60-65°C), microcapsules or ‘W/W particles containing drug dissolved in sodium hyaluronate were spontaneously formed. These were dispersed in a solution of a mixture of 5-10 per cent w/v polyvinyl alcohol, PVA (average MW 50000-106000; 98 per cent hydrolysed) and 3 per cent v/v polyethylene glycol 200 (PEG 200), and dried to form the hydrogel film casts. Our in vitro experiments in isotonic phosphate buffer solution (pH 7-4) at 37°C., showed that the release of gentamicin sulphate was dependent on concentration of LBG, and concentration or molecular weight of PVA. With the exception of PVA hydrogel matrix preparations containing 20 per cent w/v LBG, all other formulations showed a significant initial ‘burst' release of drug within 6h. The drug-containing microcapsules in the PVA hydrogel film with 20 per cent w/v LBG, exhibited an almost zero-order release of drug up to 140h. It is postulated that an effective barrier or high-density membrane enveloping the microcapsules was formed between i-C and LBG because of their unique molecular configurations. This phenomenon, together with the possible adsorption of i-C molecules at the transient oil and outer aqueous phase interface, presumably eliminated the need for a permanent oil phase and/or an O/W surfactant normally required for preparing W/O/W emulsions.     

Formulation of novel sustained release rifampicin-loaded solid lipid microparticles based on structured lipid matrices from Moringa oleifera

Abstract

Objectives: To formulate sustained release rifampicin-loaded solid lipid microparticles (SLMs) using structured lipid matrices based on Moringa oil (MO) and Phospholipon 90G (P90G).

Methods: Rifampicin-loaded and unloaded SLMs were formulated by melt homogenization and characterized in terms of particle morphology and size, percentage drug content (PDC), pH stability, stability in simulated gastric fluid (SGF, pH 1.2), minimum inhibitory concentration (MIC) and in vitro release. In vivo release was studied in Wistar rats.

Results: Rifampicin-loaded SLMs had particle size range of 32.50?±?2.10 to 34.0?±?8.40?μm, highest PDC of 87.6% and showed stable pH. SLMs had good sustained release properties with about 77.1% release at 12?h in phosphate buffer (pH 6.8) and 80.3% drug release at 12?h in simulated intestinal fluid (SIF, pH 7.4). SLMs exhibited 48.51% degradation of rifampicin in SGF at 3?h, while rifampicin pure sample had 95.5% degradation. Formulations exhibited MIC range of 0.781 to 1.562, 31.25 to 62.5 and 6.25 to 12.5?μg/ml against Salmonella typhi, Escherichia coli, and Bacillus subtilis respectively and had higher in vivo absorption than the reference rifampicin (p?<?0.05).

Conclusion: Rifampicin-loaded SLMs could be used once daily for the treatment tuberculosis.     

Colon-specific delivery of mesalazine chitosan microspheres

Mesalazine (5-ASA) is a cyclo-oxygenase inhibitor and anti-inflammatory drug effective in Crohn's disease and ulcerative-colitis. As 5-ASA is rapidly absorbed from the small intestine and it is necessary to develop a colon-specific delivery system for it. Coated chitosan microspheres were used for this purpose by an emulsion-solvent evaporation technique based on a multiple w/o/w emulsion. Four hundred milligrams of chitosan solution (3%) in dilute acetic acid (0.5?M) containing 12% 5-ASA was dispersed into 2?ml solution of cellulose acetate butyrate (CAB) in methylene chloride. The primary induced w/o emulsion was dispersed into a 1% PVA aqueous solution to produce a w/o/w multiple emulsion and was stirred for ～2.5?h. The produced microspheres were separated, washed and dried. Release of 5-ASA from microspheres was studied in different pHs 1.2, 7.4, 6.8 and 6.8 in the presence of caecal contents of rat. The average size of microspheres was 200?µm. The highest yield efficiency (80%) was seen in medium molecular weight (MW) chitosan with a 1?:?2 core/coat ratio and the greatest loading efficiency (85%) related to the microspheres of the same type of chitosan but with a 1?:?1 core/coat ratio. Decreasing the coat content and increasing chitosan Mw increased the bioadhesion significantly (p?<?0.05). Microspheres of chitosan with medium Mw and 1?:?1 core/coat that showed the greatest release of drug (near 80%) in the presence of caecal secretions with a zero-order mechanism, near zero per cent in pH 1.2 after 2?h, max 20% in pH 7.4 after 3?h and near 60% in pH 6.8 after 8?h seem suitable for site-specific delivery of 5-ASA in vitro.     

Protective efficacy of ursodeoxycholic acid nanoparticles in animal model of inflammatory bowel disease

Abstract

Context: Ursodeoxycholic acid (UDCA) exerts dose-dependent chemoprevention in colonic inflammation. Polycationic UDCA nanoparticles (UNPs) are envisaged for solubility enhancement and site directed drug delivery. Objective: The objective was to study the ameliorative efficacy of UNPs through localized delivery of the drug. Methods: UNPs were prepared through nanoprecipitation technique. Particle size, morphology, in vitro drug release and in vivo protective efficacy in inflammatory bowel disease (IBD) of these nanoparticles were studied. Results and Discussion: The average particle size was around 100?nm, and the average drug encapsulation was about 99%. In vitro drug release study shows optimal drug release in simulated colonic fluid. The lowering of tissue nitric oxide, malondialdehyde, myeloperoxidase and histology of the colon tissue supported the protective efficacy of the nanoparticles. Conclusion: This study presents the improved efficacy of UNPs in animal model of IBD due to complete release of drug at the desired site of action.     

Ulcerative proctitis: an update on the pharmacotherapy and management

Introduction: Ulcerative colitis (UC) presents as proctitis in approximately a quarter of the patients. It may progress into left-sided or extensive colitis in up to 50% of cases upon long-term follow-up.

Areas covered: Currently available data on ulcerative proctitis are summarized and critically reviewed. Extensive literature search (MEDLINE) was performed to identify relevant articles up to March 2014.

Expert opinion: The short-term goal of the treatment in UC is to induce remission, whereas long-term goals are to maintain remission and prevent disease progression. Topically administered 5-aminosalicylates (5-ASA) and corticosteroids are effective in the treatment of proctitis, although they seem to be underused in everyday practice. Locally administered 5-ASA preparations are more effective than oral compounds. The combination of topical and oral 5-ASA and steroids should be considered for escalation of treatment. Refractory patients should be re-evaluated to exclude for compliance failures, infections or proximal disease extent. True refractory or steroid-dependent patients may require immunomodulators or biological therapy. Alternative medicine can be used complementarily, while experimental approaches are reserved for patients failing conventional medication. Proctocolectomy may be the last resort of treatment. Upon long-term, 5-ASA maintenance treatment is indicated in all UC cases to prevent relapse and disease progression.     

Colon specific CODES based Piroxicam tablet for colon targeting: statistical optimization,in vivo roentgenography and stability assessment

Abstract

This study was aimed to statistically optimize CODES? based Piroxicam (PXM) tablet for colon targeting. A 3² full factorial design was used for preparation of core tablet that was subsequently coated to get CODES? based tablet. The experimental design of core tablets comprised of two independent variables: amount of lactulose and PEG 6000, each at three different levels and the dependent variable was %CDR at 12?h. The core tablets were evaluated for pharmacopoeial and non-pharmacopoeial test and coated with optimized levels of Eudragit E100 followed by HPMC K15 and finally with Eudragit S100. The in vitro drug release study of F1–F9 was carried out by change over media method (0.1?N HCl buffer, pH 1.2, phosphate buffer, pH 7.4 and phosphate buffer, pH 6.8 with enzyme β-galactosidase 120?IU) to select optimized formulation F9 that was subjected to in vivo roentgenography. Roentgenography study corroborated the in vitro performance, thus providing the proof of concept. The experimental design was validated by extra check point formulation and Diffuse Reflectance Spectroscopy revealed absence of any interaction between drug and formulation excipients. The shelf life of F9 was deduced as 12 months. Conclusively, colon targeted CODES? technology based PXM tablets were successfully optimized and its potential of colon targeting was validated by roentgenography.     

对乙酰氨基酚非pH依赖性缓释片的处方优化

目的:设计及优化非pH依赖性缓释片处方.方法:以对乙酰氨基酚为模型药物,设计不同配比的海藻酸钠和壳聚糖为混合骨架的缓释片处方,测定各处方在 0.1 mol·L-1盐酸和pH 6.8磷酸盐缓冲液中的释放度,采用多指标同步优化筛选处方.结果:优化的乙酰氨基酚缓释片处方含壳聚糖 85 mg、海藻酸钠 135 mg 时,呈现良好的体外非pH依赖性释放特征.结论:采用海藻酸钠和壳聚糖混合骨架易制得非pH依赖性缓释片,且方法简单、成本低,具有较高的实用价值.     

基于壳聚糖/海藻酸钠-聚乙烯醇的双层复合水凝胶膜伤口敷料研究

目的 制备聚乙烯醇（PVA）/海藻酸钠（SA）-聚乙烯醇（PVA）/壳聚糖（CS）双层（PAPCS）水凝胶膜伤口敷料，并进行质量评价。方法 将PVA与SA以质量比2∶1混合，配制PVA/SA混合溶液；将PVA与CS分别以质量比1∶1、2∶1、3∶1、4∶1、5∶1混合，配制不同质量比的PVA/CS混合溶液；采用涂布法制备PAPCS双层水凝胶膜伤口敷料。通过水蒸气透过率、溶胀性能、保水性、力学性能、体外凝血性能和血液相容性考察对水凝胶膜的性能进行评价、筛选PVA与CS质量比；通过傅里叶变换红外光谱检测（FTIR）和扫描电子显微镜（SEM）对PAPCS水凝胶膜的结构和形貌进行表征；通过抑菌实验比较PAPCS以及PAPCS复合载碘交联环糊精金属有机骨架（I₂@COF@PAPCS）的体外抗菌性能。结果 PVA与CS质量比为2∶1时，PAPCS水凝胶膜综合性能较好。PAPCS水凝胶膜为多孔结构，具有良好的溶胀性能、保水性以及力学性能；PAPCS水凝胶膜的水蒸气透过率为（2 643.76±91.62）g·m^-2·d^-1，接近理想范围；与PVA/SA相比，PAPCS的凝血指数显著降低（P＜0.01），为（72.93±3.58）%，溶血率小于5%，具有促进血液凝固的能力且血液相容性良好；与PVA/SA相比，PAPCS对于金黄色葡萄球菌、大肠埃希菌均有明显抑制作用，抑菌圈直径分别为（11.89±0.22）、（12.28±0.25） mm；I₂@COF@PAPCS对金黄色葡萄球菌、大肠埃希菌的抑菌圈直径分别为（21.95±1.47）、（18.89±0.81）mm，抑菌效果显著优于PAPCS（P＜0.001）。结论 采用涂布法可成功制备双层PAPCS水凝胶膜敷料，其各项性能指标良好，具有明显的凝血、抑菌效果，与I₂@COF复合使用，抑菌作用进一步增强。     

Development and characterization of colon specific drug delivery system bearing 5-ASA and camylofine dihydrochloride for the treatment of ulcerative colitis

The treatment of ulcerative colitis (inflammatory bowel disease, IBD) has been achieved by using colon specific drug delivery system bearing 5-ASA and Camylofine dihydrochloride. Chitosan microspheres were prepared separately for both the drugs using emulsion method followed by enteric coating with Eudragit^®S-100. The in vitro drug release was investigated in different simulated GIT medium. The drug release in PBS (pH7.4) and simulated gastric fluid has shown almost similar pattern and rate, whereas a significant increase in drug release (70.3?±?1.36 and 72.5?±?1.33% of 5-ASA and Camylofine, respectively) was observed in medium containing 3% rat caecal matter, after 24?h. In control study, 57.1?±?1.13% of 5-ASA and 59.2?±?1.2% of Camylofine release was observed in 24?h. For enzyme induction, rats were orally administered with 1?mL of 1% w/v dispersion of chitosan for 5 days and release rate studies were conducted in SCF with 3% w/v of caecal matter. An enhanced drug release (i.e., 92.3?±?3.81 and 95.5?±?3.52% 5-ASA and Camylofine, respectively) was observed after 24?h in dissolution medium containing 3% caecal content obtained from enzyme induced animals. In vivo data showed that microspheres delivered most of its drug load (76.55?±?2.13%) to the colon after 9?h, which reflects its targeting potential to the colon. It is concluded that orally administered microspheres of both drugs can be used together for the specific delivery of drug to the colon and reduce symptoms of ulcerative colitis.     

Design,development and in vitro-in vivo study of a colon-specific fast disintegrating tablet

Objective: Targeted delivery systems for the treatment of Inflammatory bowel disease (IBD) are designed to increase local tissue concentrations of anti-inflammatory drugs from lower doses compared with systemic administration. The objective of this study was to formulate and evaluate an oral system designed to achieve site-specific and instant drug release in the colon for effective treatment of IBD.

Materials and methods: The system consists of a core tablet containing the model drug diclofenac sodium, superdisintegrant sodium starch glycolate, and coated with enteric polymer Eudragit FS 30 D to achieve different total percentage weight gain. Drug release studies were carried out using a changing pH method. A placebo formulation containing barium sulphate in the tablet was administered to human volunteers for in vivo X-ray studies. SEM studies were performed to determine coating thickness and film topography.

Results: In vitro studies revealed that the tablet with 10% coating level released the drug after 5?h lag time corresponding to the colonic region. Tablets with 10% coating level could maintain their integrity in human volunteers for 5?h, approximating colon arrival time and release the drug instantaneously.

Discussion: Colon-targeting and instant drug release for 10% coating level was due to the dissolution of the Eudragit FS 30 D and the immediate release effect of superdisintegrant. It was observed that as the coating level increased, the lag time also increased. This was because of increased diffusion path length and tortuosity at higher coating levels.

Conclusion: An in vivo-in vitro study revealed that not only the sensitivity of the polymer to the pH environment but also the thickness of coating plays an important role in colon delivery and the tablet with 5% superdisintegrant and 10% coating level achieved the desired performance of the colon targeting.     

Preparation and characterization of nanocapsules for colon-targeted drug delivery system

Context: Nanoparticles for colon-specific drug delivery system are known for their specific accumulation in the inflamed tissue in the colon and may therefore allow a selective delivery to the site of inflammation for the treatment of inflammatory bowel disease (IBD).

Objective: The objective of this study was to formulate and evaluate nanocapsules (NC), an oral system designed to achieve site-specific and instant drug release in colon for effective treatment of IBD.

Materials and methods: Prednisolone (PD), a typical glucocorticoid, has been widely used for the treatment of IBD. In this study, nanoprecipitation method was used to prepare polymeric NC of PD with pH responsive polymer Eudragit S100. The effect of several formulation variables such as surfactant, oil, and polymer on the PD-NC properties (average size, drug release rate, and drug entrapment) was investigated. In vitro drug release study was done by changing pH method and an in vivo study on rat was done to ascertain efficiency of PD-NC to release drug specifically in colon.

Results and discussion: The optimized formulations lead to the preparation of PD-NC with a mean size of 567.87?nm, high encapsulation efficiency of 90.21%. In vitro studies reveal that NC releases the drug after 4.5-h lag time corresponding to time to reach colonic region, and in vivo studies show that NC release drug after 3-h lag time in rat corresponds to arrival in colon.

Conclusion: The above NC formulation of PD is the targeted drug to the colon and may provide effective way of treatment of colonic disease.     

Concentration dependence of 5-aminosalicylic acid pharmacological actions in intestinal mucosa after oral administration of a pH-dependent formulation

Asacol, a medication that delivers delayed release 5-aminosalicylic acid (5-ASA), is a useful therapeutic agent for inflammatory bowel disease (IBD), but the relationship between its pharmacological actions and intestinal concentrations has not been studied in detail. Therefore, our aim was to assess 5-ASA's pharmacological actions as a function of its concentration at its target site. We first evaluated 5-ASA's release profiles in vitro by the paddle method and found that Asacol starts to release 5-ASA at pH ≥ 7. Orally administered Asacol pharmacokinetic parameters were evaluated in dogs. Asacol's T(max) was much longer than that of the time-dependent release 5-ASA formulation. We also determined 5-ASA's distribution in the intestinal mucosa and found that it is effectively delivered there by Asacol. These results indicated that Asacol released 5-ASA in a pH-dependent manner, resulting in efficient delivery to the large intestine. We also compared the mucosal 5-ASA concentrations with the IC(50) values for scavenging free radicals or suppressing LTB(4) production. The 5-ASA concentration in the large intestine was higher than IC(50) values necessary to suppress inflammatory processes. We also report the release characteristics of Asacol and the targeted delivery of 5-ASA to affected sites in IBD patients.     

Solid super saturated self-nanoemulsifying drug delivery system (sat-SNEDDS) as a promising alternative to conventional SNEDDS for improvement rosuvastatin calcium oral bioavailability

ABSTRACT

Objective: This study aims to illustrate the applicability of solid supersaturated self-nanoemulsifying drug delivery system (sat-SNEDDS) for the improvement of rosuvastatin calcium (RC) oral bioavailability.

Methods: Different sat-SNEDDS were prepared by incorporating different ratios of RC into SNEDDS using tween80/PEG400 (77.2%) as surfactant/cosurfactant mixture and garlic /olive oil (22.8%) as oil phase. The prepared systems were characterized viz; size, zeta potential, TEM and stability. Various hydrophilic and hydrophobic carriers were employed to solidify the optimized RC sat-SNEDDS. The influence of the carrier was investigated by SEM, XRPD, DSC, flow properties, in vitro precipitation, drug release and oral bioavailability study.

Results: The adsorption of the stable positively charged nanocarrier RC sat-SNEDDS onto solid carriers provided free flowing amorphous powder. The carrier could amend the morphological architecture and in vitro release of the RC solid sat-SNEDDS. Hydrophobic carriers as microcrystalline cellulose 102 (MCC) showed superior physical characters and higher dissolution rate over hydrophilic carriers as maltodextrin with respective T_100% 30 min and 45 min. The rapid spontaneous emulsification, the positively nanosized MCC-sat-SNEDDS improved oral bioavailability of RC by 2.1-fold over commercial tablets.

Conclusion: Solid MCC-sat-SNEDDS combined dual benefits of sat-SNEDDS and solid dosage form was successfully optimized to improve RC oral bioavailability.     

A novel electrospun membrane based on moxifloxacin hydrochloride/poly(vinyl alcohol)/sodium alginate for antibacterial wound dressings in practical application

This study reports on the performance of sodium alginate (SA)/poly(vinyl alcohol) (PVA)/moxifloxacin hydrochloride (MH) nanofibrous membranes (NFM) capable of providing antibacterial agent delivery for wound-dressing applications. The aim of this work was to prepare antibacterial NFM with good permeability properties by employing PVA and SA as carriers. A group of 12% PVA/2% SA solutions blended in various ratios (8:2, 7:3, 6:4, 5:5 and 4:6, v/v) and containing 0.5, 1, 2 or 4 wt% MH were studied for electrospinning into nanoscale fibermats. The optimum ratio found to form smooth fibers with uniform fibrous features was 6:4. The drug release behavior of the electrospun, the antibacterial effects on Pseudomonas aeruginosa and Staphylococcus aureus and the animal wound dressing capabilities were also investigated. As much as 80% of the MH was released from the electrospun after 10?h of incubation at 37?°C. In addition, the NFM with 0.5 MH exhibited less activity, whereas those with higher concentrations of MH exhibited greater antibacterial effect. Furthermore, the MH-loaded electrospun accelerated the rate of wound dressing compared to other groups. The results of the in vitro and in vivo experiments suggest that MH/PVA/SA nanofibers might be an interesting bioactive wound dressing for clinical applications.