Effects of Quadruple Therapy Combined with Probiotics on Helicobacter Pylori-Related Peptic Ulcer.

The present study was designed to observe the effect of quadruple therapy combined with probiotics on Helicobacter pylori-related peptic ulcer. The patients in the control group (n = 90) were given regular quadruple therapy including proton pump inhibitor ilaprazole enteric-coated tablet + two antibiotics amoxicillin dispersible tablet and metronidazole tablet + colloidal bismuth pectin capsule for 2 weeks. Patients in the study group (n = 90) were given abovementioned quadruple therapy combined with probiotics live combined Bifidobacterium, Lactobacillus, and Enterococcus Capsules, oral for 2 weeks. Then Hp clearance rate, recurrence rate, levels of gastrointestinal hormone makers, and advance reactions between two groups were compared. At the 2nd week after the treatment, the Helicobacter pylori clearance rate in the study group (87.79%) was significantly higher than the control group (78.89%), and the total recurrence rate in the study group (6.67%) was significantly lower than the control group (13.33%) (P < 0.05). Serum gastrin and motilin expression were lower, and somatostatin expressions was significantly higher than those in the control group (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). In summary, quadruple therapy combined with probiotics in the treatment of Helicobacter pylori-related peptic ulcer can improve the Helicobacter pylori clearance rate, reduce the Helicobacter pylori recurrence rate, and is beneficial to improving the level of gastrointestinal hormones, with certain safety.

Chylomicrons-Simulating Sustained Drug Release in Mesenteric Lymphatics for the Treatment of Crohn's-Like Colitis.

BACKGROUND AND AIMS: Alteration to both the structures and functions of mesenteric lymphatic vessels is a typical hallmark of Crohn's disease [CD]. Dysfunctional lymphatics was observed in patients with both CD and experimental colitis, suggesting mesenteric lymphatics could be potential therapeutic targets. This study aimed to develop a nano-delivery system which can enhance drug delivery in mesenteric lymphatic tissue [MLT] and evaluate the therapeutic effects in Crohn's colitis. METHODS: We designed a mesoporous silica nanoparticle [MSN] conjugated with long-chain fatty acid [LMSN] and covered with enteric coating [ELMSN] which can be specifically transported via the mesenteric lymphatic system. The therapeutic efficacy of laquinimod-loaded nanoparticles [LAQ@ELMSN] was evaluated in the well-established interleukin [IL]-10-/- spontaneous experimental colitis. RESULTS: ELMSNs induced sustainable drug release that markedly increased drug concentration in MLT. In experimental colitis, the lymphatics-targeting drug delivery system suppressed lymphangitis and promoted lymphatic drainage. The downregulation of pro-inflammatory cytokines and the downstream NF-κB-related proteins efficiently inhibited lymphangiogenesis and restored tight junctions of mesenteric lymphatic vessels [MLVs]. LAQ@ELMSN showed a superior therapeutic effect in ameliorating intestinal inflammation compared with free drug administration. Alteration of gut microbiota and metabolites in experimental colitis was also reversed by LAQ@ELMSN. CONCLUSION: Our study demonstrates a convenient, orally administered drug delivery system which enhances drug release in MLT. The results confirm the contribution of the mesenteric lymphatic system to the pathogenesis of gut inflammation and shed light on the application of lymphatics-targeting drug delivery therapy as a potential therapeutic strategy for CD treatment.

Is Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium Justifiable for Gastrointestinal Quality of Life?

BACKGROUND: Globally, enteric-coated mycophenolate sodium (EC-MPS) is replacing mycophenolate mofetil (MMF) in maintenance immunosuppressant regimens. The predominant reason for conversion is the purported improvement in gastrointestinal (GI) quality of life. This paper considers the level of bias associated with studies comparing EC-MPS and MMF for GI-related improvement and provides insight into whether conversion is supported by evidence. METHODS: Using a pre-determined protocol, a literature search was conducted. Full-text review, data extraction and risk of bias analysis was conducted by two independent authors using the Cochrane domain-based evaluation of risk of bias. The review was reported according to the preferred reporting items for systematic reviews and meta-analyses. RESULTS: Twenty-nine studies were included in risk of bias analysis. Of these, only three were deemed a low risk of bias. Across these three studies, there were no statistically significant differences in the proportion of GI-related adverse events nor was there a significant difference in the GI-related quality of life between EC-MPS- and MMF-treated patients in these data. CONCLUSION: There was a high risk of bias across the 29 studies investigating conversion from MMF to EC-MPS for potential improvement in GI-related quality of life. The consolidated results of the three studies with low risk of bias suggest no evidence to convert patients stabilised on MMF. If a patient experiences GI-related adverse events whilst taking MMF, other methods should be explored before conversion to EC-MPS.

Development of an enteric nanoparticle of marine sulfated polysaccharide propylene glycol alginate sodium sulfate for oral administration: formulation design, pharmacokinetics and efficacy.

OBJECTIVES: Propylene glycol alginate sodium sulfate (PSS) is poorly absorbed by oral administration due to its large molecular weight and slightly degradability in stomach acidic environment. Here, a novel enteric-coated nano formulation of PSS (enteric PSS-NP) was prepared to improve its bioavailability and efficacy. METHODS: The enteric PSS-NP was prepared by double (W1 /O/W2 ) emulsion and solvent evaporation method. The drug release characteristics in vitro were studied in artificial gastrointestinal fluid. And the pharmacokinetics and efficacy of enteric PSS-NP were separately investigated in normal rats and type 2 diabetic db/db mice. KEY FINDINGS: The enteric PSS-NP were in spherical shape and exhibited negative zeta potential. The releasing characteristics of enteric PSS-NP in vitro showed that it possessed a strong pH-sensitive release character. Single-dose (50 mg/kg) oral pharmacokinetic study in rat plasma showed that enteric PSS-NP could improve the relative bioavailability significantly compared with PSS solution. Furthermore, the efficacy of enteric PSS-NP in vivo was better than that of PSS solution at equivalent doses. CONCLUSIONS: The study showed that enteric-coated formulation of PSS had the intestinal-targeted absorption and improved pharmacodynamics, which indicated that enteric PSS-NP could be developed into a new formulation product in the future.

Development and characterization of pullulan-polymethacrylate free films as potential material for enteric drug release

ABSTRACT Free films of pullulan-polymethacrylate associations were produced by casting process to develop a novel target-specific material. For characterization, tests of water vapor permeability, swelling index, infrared absorption spectroscopy, thermogravimetric analysis, scanning electron microscopy and mechanical analysis were performed. The polysaccharide concentration directly influenced vapor permeability and swelling, increasing the values of the latter up to five times when added in a proportion of 20% (per weight). The individual properties of each polymer were maintained, and chemical interactions were not detected. The films were found to be thermally stable and they had unaltered mechanical properties with the addition of the polysaccharide. The microscopic analysis revealed rugosity that was proportional to pullulan and disorganization of the polymer network at pH 6.8. These results suggest that this novel material has potential for enteric drug release because of synergism between pH and enzyme dependence.

Colon targeted guar gum compression coated tablets of flurbiprofen: formulation, development, and pharmacokinetics.

The rationale of the present study is to formulate flurbiprofen colon targeted compression coated tablets using guar gum to improve the therapeutic efficacy by increasing drug levels in colon, and also to reduce the side effects in upper gastrointestinal tract. Direct compression method was used to prepare flurbiprofen core tablets, and they were compression coated with guar gum. Then the tablets were optimized with the support of in vitro dissolution studies, and further it was proved by pharmacokinetic studies. The optimized formulation (F4) showed almost complete drug release in the colon (99.86%) within 24 h without drug loss in the initial lag period of 5 h (only 6.84% drug release was observed during this period). The pharmacokinetic estimations proved the capability of guar gum compression coated tablets to achieve colon targeting. The C(max) of colon targeted tablets was 11956.15 ng/mL at T max of 10 h whereas it was 15677.52 ng/mL at 3 h in case of immediate release tablets. The area under the curve for the immediate release and compression coated tablets was 40385.78 and 78214.50 ng-h/mL and the mean resident time was 3.49 and 10.78 h, respectively. In conclusion, formulation of guar gum compression coated tablets was appropriate for colon targeting of flurbiprofen.

Evaluation of enteric-coated tablets as a whole cell inactivated vaccine candidate against Vibrio cholerae.

A vaccine candidate against cholera was developed in the form of oral tablets to avoid difficulties during application exhibited by current whole cell inactivated cholera vaccines. In this study, enteric-coated tablets were used to improve the protection of the active compound from gastric acidity. Tablets containing heat-killed whole cells of Vibrio cholerae strain C7258 as the active pharmaceutical compound was enteric-coated with the polymer Kollicoat(®) MAE-100P, which protected them efficiently from acidity when a disintegration test was carried out. Enzyme-linked immunosorbent assay (ELISA) anti-lipopolysaccharide (LPS) inhibition test and Western blot assay revealed the presence of V. cholerae antigens as LPS, mannose-sensitive haemagglutinin (MSHA) and outer membrane protein U (Omp U) in enteric-coated tablets. Immunogenicity studies (ELISA and vibriocidal test) carried out by intraduodenal administration in rabbits showed that the coating process of tablets did not affect the immunogenicity of V. cholerae-inactivated cells. In addition, no differences were observed in the immune response elicited by enteric-coated or uncoated tablets, particularly because the animal model and immunization route used did not allow discriminating between acid resistances of both tablets formulations in vivo. Clinical studies with volunteers will be required to elucidate this aspect, but the results suggest the possibility of using enteric-coated tablets as a final pharmaceutical product for a cholera vaccine.

Omeprazole impairs the absorption of mycophenolate mofetil but not of enteric-coated mycophenolate sodium in healthy volunteers.

In 2 crossover studies, 12 healthy volunteers (6 male/6 female) received a single oral dose of mycophenolate mofetil (MMF) 1000 mg or an equimolar dose of enteric-coated mycophenolate sodium (EC-MPS) 720 mg fasting with and without coadministered omeprazole 20 mg bid. The plasma concentrations of mycophenolic acid (MPA) and of the inactive metabolite mycophenolic acid glucuronide (MPA-G) were measured by high-performance liquid chromatography (HPLC). In addition, dissolution of MMF 500 mg or EC-MPS 360 mg tablets was determined using an USP paddle apparatus in aqueous buffer of pH 1 to 7. The bioavailability of MPA following administration of MMF or EC-MPS was similar except for the time to peak concentration, which was longer in the EC-MPS group. Concomitant treatment with omeprazole lowered significantly C(max) and AUC(12h) of MPA following administration of MMF. The pharmacokinetics of EC-MPS was not affected. Dissolution of MMF in aqueous buffer decreased dramatically at pH above 4.5. The EC-MPS tablet was stable up to pH 5. Above, EC-MPS was quantitatively disintegrated and MPS quantitatively dissolved. There is strong evidence that impaired absorption of MMF with concomitant proton pump inhibitors is due to incomplete dissolution of MMF in the stomach at elevated pH.

The evaluation of coated granules to mask the bitter taste of dihydroartemisinin / A avaliação de grânulos revestidos para mascarar o sabor amargo da diidroartemisina

The purpose of this study was to mask the bitter taste imparted by dihydroartemisinin (DHA) by the use of different coating materials. Trial-1 and trial-2 were conducted to prepare the DHA granules. The granules produced from trial-1 were irregular in shape and smaller in size while the trial-2 granules were more regular and larger in size. The granules obtained from both trials were then coated with two different coating methods, namely A and B, depending upon coating material. The trial-2 granules showed better flow properties than trial-1 granules. In vitro dissolution studies in phosphate buffer at pH 6.8 revealed that granules of trial-2B released only 34 percent ± 3 DHA in two minutes compared with trial-1A (57 percent ± 2), trial-1B (48 percent ± 2) and trial-2A (53 percent ± 7). The pleasant taste perception (PTP) test also confirmed the taste masking efficacy of trial-2B (P < 0.05). Scanning electron microscopy (SEM) revealed the more regular and smooth surface of trial-2B granules. In addition, the differential thermal and thermogravimetric analysis (TG-DTA) confirmed no interaction between the materials and pure DHA. DHA has shown its characteristic peaks in the x-ray diffraction (XRD) patterns which were also prominent in all the granules. In conclusion, the granules obtained from trial-2B displayed considerable decrease in the bitter taste of DHA thereby fulfilling the purpose of this study.

O objetivo deste estudo foi o de mascarar o gosto amargo característico da diidroartemisinina (DHA) pelo uso de diferentes materiais de revestimento. Experimento-1 e experimento-2 foram realizados para preparar grânulos de DHA. Os grânulos produzidos pelo experimento-1 mostraram-se irregulares e menores se comparados aos obtidos pelo experimento-2, que foram mais regulares e maiores. Os grânulos obtidos em ambos os experimentos foram, então, revestidos por dois métodos distintos de revestimento, designados como A e B, dependendo do material de revestimento empregado. Os grânulos do experimento-2 mostraram melhor propriedade de fluxo que os obtidos no experimento-1. Estudos de dissolução in vitro em tampão fosfato pH 6,8 revelaram que grânulos do experimento-2B liberaram apenas 34 por cento ± 3 da DHA em dois minutos se comparado com experimento-1A (57 por cento ± 2), experimento-1B (48 por cento ± 2) e experimento-2A (53 por cento ± 7). A Análise Sensorial quanto ao sabor (Pleasant Taste Perception - PTP) também confirmou a eficácia do experimento-2B (P <0,05) em mascarar o gosto amargo da DHA. Microscopia Eletrônica de Varredura (SEM) revelou a superfície mais regular e lisa dos grânulos obtidos pelo experimento-2B. Além disso, Análise Termogravimétrica e Análise Térmica Diferencial (TG-DTA) confirmaram que não há nenhuma interação entre os materiais e a DHA pura. DHA mostrou seus picos característicos na Difração de Raios X (XRD) em padrões que também foram proeminentes em todas as amostras. Em conclusão, os grânulos obtidos pelo experimento-2B exibiram diminuição considerável no gosto amargo da DHA, o que era o propósito deste estudo.

The glucose-lowering potential of exendin-4 orally delivered via a pH-sensitive nanoparticle vehicle and effects on subsequent insulin secretion in vivo.

Exendin-4 is a potent insulinotropic agent in diabetes patients; however, its therapeutic utility is limited due to the frequent injections required. In this study, an orally available exendin-4 formulation, using an enteric-coated capsule containing pH-responsive NPs, was developed. Following oral administration of (123)I-labeled-exendin-4 loaded NPs in rats, the biodistribution of the administered drug was investigated using a dual isotope dynamic SPECT/CT scanner. The results showed that the radioactivity of (123)I-exendin-4 propagated from the esophagus, stomach, and small intestine and then was absorbed into the systemic circulation; with time progressing, (123)I-exendin-4 was metabolized and excreted into the urinary bladder. In the in vivo dissolution study, it was found that the enteric-coated capsule remained intact while in the stomach; the capsule was completely dissolved in the proximal segment of the small intestine and the loaded contents were then released. Oral administration of the capsule containing exendin-4 loaded NPs showed a maximum plasma concentration at 5 h after treatment; the bioavailability, relative to its subcutaneous counterpart, was found to be 14.0 ± 1.8%. The absorbed exendin-4 could then stimulate the insulin secretion and provide a prolonged glucose-lowering effect. The aforementioned results suggest that the orally available exendin-4 formulation developed warrants further exploration as a potential therapy for diabetic patients.

In-vitro characterization of 5-aminosalicylic acid release from MMX mesalamine tablets and determination of tablet coating thickness.

INTRODUCTION: Substantial variability in gastrointestinal pH is observed in patients with ulcerative colitis (UC). We characterized the effect of pH on 5-aminosalicylic acid (5-ASA) release from MMX mesalamine tablets (Shire Pharmaceuticals Inc., Wayne, PA, USA), examined thickness/uniformity of tablet film coatings, and explored the influence of simulating altered gastrointestinal motility. METHODS: Nondestructive, three-dimensional, terahertz pulse imaging (TPI) was used to characterize the film coating of three lots of MMX mesalamine tablets (n=36). Thereafter, 5-ASA release from these tablets was evaluated using United States Pharmacopeia (USP) apparatus II at pH 6.8 and 7.2. Onset of tablet film-coat breach and mean dissolution time were determined for each lot. 5-ASA release was also assessed at three different paddle rotation speeds (50, 75, and 100 rpm) at pH 7.2. RESULTS: The mean ± SD film-coating thickness of the three lots of MMX mesalamine tablets were 109.2 ± 16.8, 113.1 ± 19.5, and 113.8 ± 19.8 µM, respectively. At pH 6.8 (100 rpm), the onset of film-coat breach was 10-30 minutes, whereas at pH 7.2 this was observed within 10 minutes. 5-ASA release was uniform at both pH conditions, with minimal lot-to-lot variability. Complete drug release was achieved within 6 hours under both pH conditions. 5-ASA release increased in proportion with paddle speed, but remained prolonged at all speeds. CONCLUSION: 5-ASA release from MMX mesalamine is unaffected by normal variations in simulated intracolonic pH. The dissolution profile of 5-ASA from MMX mesalamine tablets may be attributed to consistent outer film coatings and the hydrogel-forming matrix that controls the drug release after dissolution of the film coating.

Effects of different doses, enteric-coated preparation of aspirin, and sex on urinary 11-dehydrothromboxane B2 in healthy volunteers.

There is scarce information about the effects of different doses and enteric-coated preparation of aspirin on platelet function, especially in Asian people, evaluated by the measurement of urinary 11-dehydrothromboxane B2 (dTXB2). The objective of the present study was to assess the effects of different doses, enteric-coated preparation of aspirin, sex and also the effects of timing of urine collection on urinary dTXB2 level in healthy volunteers. Thirty healthy volunteers were included. Each volunteer took three preparations of aspirin (aspirin 81 mg, enteric-coated aspirin 300 mg and aspirin 300 mg) for 7 days. Urine dTXB2 level was measured at baseline, day 3, and day 7 after taking each preparation of aspirin. There was no significant difference in the effects of different doses of aspirin (81 vs. 300 mg, 50.7 vs. 61.8 ng/mmol creatinine, P = 0.248), preparations (enteric-coated vs. nonenteric-coated aspirin, 61.8 vs. 67.9 ng/mmol creatinine, P = 0.527) and time of urine collection (day 3 vs. day 7, 51.7 vs. 49.9 ng/mmol creatinine, P = 0.448). Female volunteers showed a trend to have higher urinary dTXB2 than male volunteers at baseline and after taking aspirin. This study showed no significant difference in urinary dTXB2 level after taking different doses and enteric-coated preparation of aspirin in healthy volunteers.

Enteric-coated mycophenolate sodium.

IMPORTANCE OF THE FIELD: Mycophenolic acid (MPA) therapy is a fundamental component of most post-transplant immunosuppressive regimens. Side effects, however, are common and frequently necessitate dose reductions or discontinuations. AREAS COVERED IN THIS REVIEW: Enteric-coated mycophenolate sodium (EC-MPS) is designed to improve the gastrointestinal (GI) tolerability of MPA. This review assesses the pharmacology, efficacy and safety of EC-MPS. WHAT THE READER WILL GAIN: An understanding of the use of EC-MPS in solid organ transplantation and the key trials examining the GI impact of EC-MPS versus the immediate-release mycophenolate mofetil (MMF) formulation. The article also addresses the possible impact of proton pump inhibitor therapy, and the optimal MPA dose with different concomitant immunosuppressants. TAKE HOME MESSAGE: Evidence from blinded trials using standard reporting measures or patient-reported outcomes has not confirmed a significant improvement in the GI symptom burden using EC-MPS. Several open-label studies, however, have consistently shown an improvement in GI tolerability with EC-MPS, which can permit restoration of the optimal MPA dose. EC-MPS has equal efficacy and possibly a different tolerability profile to MMF, thus offering a choice to physicians and their patients, particularly those experiencing MMF-related GI symptoms, diabetic patients or those in whom an MPA dose reduction is required.

Development of enteric coated tablets from spray dried extract of feverfew (Tanacetum parthenium L) / Desenvolvimento de comprimidos de revestimento entérico de extrato de produto seco por aspersão de matricária (Tanacetum parthenium L)

Tanacetum parthenium (feverfew) is an herb that is commercialized worldwide as a therapeutic treatment for migraine. Its pharmacological effect is mainly due to the presence of the sesquiterpene lactone parthenolide as well as of flavonoids. So far, there are no studies on standardization of pre-formulations or phytomedicines containing this herb. The present study aimed at developing a pre-formulation using a standardized spray-dried extract of feverfew and further designing and standardizing enteric coated tablets. In this work, the spray-dried extract of feverfew was evaluated for its parthenolide, santin and total flavonoid content, parthenolide solubility, particle size, tapped density, hygroscopicity, angle of repose and moisture content. Tablets containing the spray-dried extract were tested for their average weight, friability, hardness, and disintegration time. The total flavonoid and parthenolide contents in the spray-dried extract were 1.31 percent and 0.76 percent w/w, respectively. The spray-dried extract presented consistent pharmacotechnical properties and allowed its tableting by direct compression. Tablet properties were in accordance with the proposed specifications. The procedures described herein can be used to prepare and evaluate pre-formulations of feverfew with adequate properties for the development of a high-quality phytomedicine.

Tanacetum parthenium (tanaceto) é uma planta medicinal comercializada no mundo todo para tratamento de enxaqueca. Seu efeito farmacológico é creditado principalmente à lactona sesquiterpênica partenolídeo e flavonóides. Até o momento não existem estudos sobre a padronização de pré-formulações ou o desenvolvimento de fitoterápicos com tanaceto. Logo, o objetivo deste trabalho foi obter comprimidos de revestimento entérico a partir de extrato seco e padronizado de tanaceto. Neste trabalho, o extrato seco do tanaceto obtido pelo método de spray drying foi avaliado quanto ao teor de partenolídeo, presença da santina, teor de flavonóides totais, solubilidade do partenolídeo, tamanho de partícula, ângulo de repouso, densidade, análise higroscópica e teor de umidade. A partir do extrato seco obtiveram-se comprimidos que foram revestidos em leito de jorro. Os comprimidos revestidos foram avaliados com relação ao peso médio, friabilidade, dureza e desintegração. O teor de flavonóides totais e de partenolídeo no extrato seco foram 1,31 por cento e 0,76 por cento (p/p), respectivamente. O extrato seco apresentou características farmacotécnicas satisfatórias permitindo a obtenção de comprimidos pelo método de compressão direta. As propriedades dos comprimidos revestidos estão de acordo com as especificações da literatura. Os procedimentos utilizados nesse trabalho podem ser utilizados para obter extrato seco e fitoterápicos de T. parthenium com alto padrão de qualidade.

Effects of anethum graveolens and garlic on lipid profile in hyperlipidemic patients.

BACKGROUND: hyperlipidemia as a major risk factor of atherosclerosis is treated with different drugs. Concerning length of therapy and vast majority of side effects, herbal medication may be suitable substitute for these drugs. METHODS: In this single-blind, placebo controlled study, lipid profiles of 150 hyperlipidemic patients in cardiology outpatient department of Shiraz University of Medical Sciences were checked at same conditions. They were divided into three equal groups randomly (each composing of 50 patients). They were given enteric-coated garlic powder tablet (equal to 400 mg garlic, 1 mg allicin) twice daily, anethum tablet (650 mg) twice daily, and placebo tablet. All patients were put on NCEP type Pi diet and Six weeks later, lipid profiles were checked. RESULTS: In garlic group: total cholesterol (decreased by 26.82 mg/dl, 12.1% reduction, and P-value: .000), and LDL-cholesterol (decreased by 22.18 mg/dl, 17.3% reduction, and P-value: .000) dropped. HDL-cholesterol (increased by 10.02 mg/dl, 15.7% increase, and P-value: .000) increased. Although triglyceride dropped by 13.72 mg/dl (6.3%) but this was not significant statistically (P-value: .222). In anethum group: surprisingly, triglyceride increased by 14.74 mg/dl (6.0%). Anethum could reduce total cholesterol by 0.4 % and LDL-cholesterol by 6.3% but these were not significant statistically (P-value: .828, and .210, respectively). CONCLUSION: Anethum has no significant effect on lipid profile, but garlic tablet has significant favorable effect on cholesterol, LDL-cholesterol, and HDL-cholesterol. Garlic may play an important role in therapy of hypercholesterolemia.

Enteric-coated mycophenolate sodium: tolerability profile compared with mycophenolate mofetil.

Mycophenolate mofetil is one of the most frequently used immunosuppressive drugs in solid organ transplantation. Although the adverse effect profile of mycophenolate mofetil is comparatively benign, gastrointestinal adverse effects are a major concern. The adverse effects may require a dose reduction or discontinuation, thus limiting its clinical efficacy. Enteric-coated (EC) mycophenolate sodium is a new formulation of mycophenolic acid (MPA) that delivers the active moiety MPA, the same active moiety delivered by mycophenolate mofetil. It has been developed to help protect the upper gastrointestinal tract. It is implied that a reduction of adverse drug effects as well as a reduction of dose may improve efficacy and compliance. Noncompliance is often underestimated in solid organ transplant recipients, and adverse drug effects increase medication nonadherence. Recent clinical trials comparing EC mycophenolate sodium and mycophenolate mofetil in kidney recipients reported similar rates of efficacy and adverse effects. It is noteworthy that systemic MPA exposure is higher with EC mycophenolate sodium than with mycophenolate mofetil, without increased gastrointestinal toxicity. This finding is quite surprising, because part of MPA-associated gastrointestinal toxicity is related to its antiproliferative effect on enterocytes. However, enteric coating of MPA did not markedly reduce the number of gastrointestinal adverse effects. Further studies focusing on dosage, therapeutic drug monitoring and immunosuppressive regimens may reveal benefits of EC mycophenolate sodium for optimal individualised immunosuppression and improved compliance. At present, EC mycophenolate sodium is an alternative immunosuppressant to mycophenolate mofetil in kidney transplant recipients with an almost identical efficacy and safety profile.

A novel crosslinkable polymer as drug-loaded coating for biomedical device.

A novel copolymer has been synthesized by the radical polymerization of poly (ethylene oxide) methacrylate, stearyl methacrylate, hydroxypropyl methacrylate and trimethoxysilylpropyl methacrylate. The polymer was characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance (1H-NMR) spectroscopy and gel permeation chromatography. The crosslinkable coating was prepared by dip-coating 5mg/ml solution in tetrahydrofuran onto glass substrate. A stable crosslinked coating was obtained after curing the coating at 70 degrees C for 9 h. Contact angle results indicated the possible reorganization of the surface amphiphilic molecule which interpreted the excellent biocompatibility revealed by the results of the platelet adhesion and plasma recalcification time. Rhodamine S and Cibacron Blue were used as model drugs to prepare drug-containing coating at the same conditions. Drug-releasing curves indicated that the mechanism of the release is approximately Fickian release.

Antiplatelet effect of aspirin in patients with cerebrovascular disease.

BACKGROUND AND PURPOSE: Aspirin is used commonly to prevent ischemic strokes and other vascular events. Although aspirin is considered safe and effective, it has limited efficacy with a relative risk reduction of 20% to 25% for ischemic stroke. We sought to determine if aspirin as currently used is having its desired antiplatelet effects. METHODS: We ascertained patients with cerebrovascular disease who were taking only aspirin as an antiplatelet agent. Platelet function was evaluated using a platelet function analyzer (PFA-100). PFA test results were correlated with aspirin dose, formulation, and basic demographic factors. RESULTS: We ascertained 129 patients, of whom 32% were taking an enteric-coated aspirin preparation and 32% were taking low-dose (< or =162 mg/d) aspirin. For the entire cohort, 37% of patients had normal PFA-100 results, indicating normal platelet function. For the patients taking low-dose aspirin, 56% had normal PFAs compared with 28% of those taking > or =325 mg/d of aspirin, while 65% of patients taking enteric-coated aspirin had normal PFAs compared with 25% taking an uncoated preparation (P<0.01 for both comparisons). Similar results were obtained if PFA results were analyzed using mean closure times (low-dose aspirin, 183 sec; high-dose aspirin, 233 sec; enteric-coated, 173 sec; uncoated, 235 sec; P<0.01 for comparisons). Older patients and women were less likely to have a therapeutic response to aspirin, independent of aspirin dose or formulation. CONCLUSIONS: A significant proportion of patients taking low-dose aspirin or enteric-coated aspirin have normal platelet function as measured by the PFA-100 test. If these results correlate with clinical events, they have broad implications in determining how aspirin is used and monitored.

Enteric-coated pellets of F4 fimbriae for oral vaccination of suckling piglets against enterotoxigenic Escherichia coli infections.

To prevent enterotoxigenic Escherichia coli (ETEC) induced postweaning diarrhoea, the piglet needs an active mucosal immunity at the moment of weaning. In the present study, the feasibility of oral vaccination of suckling piglets against F4+ETEC infection with F4 fimbriae was studied. Furthermore, oral vaccination with enteric-coated pellets of F4 fimbriae was compared to vaccination with F4 fimbriae in solution. Therefore, piglets were orally administered 1mg F4 fimbriae in pellets or in solution during three successive days at the age of 7 and 21 days, whereas control piglets were not vaccinated. Five days postweaning (33 days of age), all animals were orally challenged with F4+ETEC. Despite the induction of an immune response upon oral administration of both F4 fimbriae in pellets as in solution, the colonisation of the small intestine by F4+ETEC upon oral challenge could not be prevented. However, a marginal but significant reduction in F4+ E. coli faecal excretion was found in the piglets vaccinated with F4 fimbriae in pellets, indicating that the use of an enteric-coat which protects the F4 fimbriae against inactivation by milk factors and degradation by enzymes and bile improves vaccination.

Validação do método espectrofotométrico da pentoxifilina em comprimidos revestidos de 400mg / Spectrophotometric method validation of pentoxyfiline 400mg coated tablets

Validou-se um método espectrofotométrico para doseamento de pentoxifilina em comprimidos de 400 mg, utilizando-se tampão pH 1,2. O fármaco apresentou absorção máxima em 273 nm. O método proposto obedeceu a lei de Lambert Beer na faixa de concentração de 11,0 a 20 'mü'/mL (r=0,9996). Não houve interferência dos excipientes das formulações, sendo o método preciso e exato...