Search

Colonic drug delivery offers numerous pharmaceutical opportunities, including direct access to local therapeutic targets and drug bioavailability benefits arising from the colonic epithelium's reduced abundance of cytochrome P450 enzymes and particular efflux transporters. Current workflows for developing colonic drug delivery systems involve time-consuming, low throughput in vitro and in vivo screening methods, which hinder the identification of suitable enabling materials. Polysaccharides are useful materials for colonic targeting, as they can be utilised as dosage form coatings that are selectively digested by the colonic microbiota. However, polysaccharides are a heterogeneous family of molecules with varying suitability for this purpose. To address the need for high-throughput material selection tools for colonic drug delivery, we leveraged machine learning (ML) and publicly accessible experimental data to predict the release of the drug 5-aminosalicylic acid from polysaccharide-based coatings in simulated human, rat, and dog colonic environments. For the first time, Raman spectra alone were used to characterise polysaccharides for input as ML features. Models were validated on 8 unseen drug release profiles from new polysaccharide coatings, demonstrating the generalisability and reliability of the method. Further, model analysis facilitated an understanding of the chemical features that influence a polysaccharide's suitability for colonic drug delivery. This work represents a major step in employing spectral data for forecasting drug release from pharmaceutical formulations and marks a significant advancement in the field of colonic drug delivery. It offers a powerful tool for the efficient, sustainable, and successful development and pre-ranking of colon-targeted formulation coatings, paving the way for future more effective and targeted drug delivery strategies. [Display omitted] • A new Raman spectrum processing pipeline for effective Machine Learning. • Raman spectra of polysaccharide coatings can successfully predict 5-ASA release. • ML model is robust in human, rat and dog IBD-simulated colonic environments. • Model interpretation revealed coating molecular properties influencing 5-ASA release. [ABSTRACT FROM AUTHOR]

The incidence of ulcerative colitis (UC) is increasing worldwide and therapeutic drugs for UC are limited. Improvement of microbiome composition with the use of probiotics has the potential to increase the therapeutic index of UC drugs. Several lines of evidence suggested that Bifidobacterium significantly improve colitis by restoring the altered gut microbiota in DSS-treated mice, however the adjuvant effect of Bifidobacterium with UC drugs remains unknown. In this study, we tested the adjuvant potential of probiotic selenium-enriched Bifidobacterium Longum DD98 (SeDD98) on Mesalazine and Cyclosporin A (CsA) two medications used in the treatment of UC. We found that SeDD98 significantly improved the efficacy of Mesalazine and CsA in UC. The combination of SeDD98 and CsA showed the strongest efficacy in decreasing colitis histological scores, inflammation, and oxidative stress. Next we demonstrated that the combination of SeDD98 and CsA shifted the gut microbiota composition and increased with higher alpha diversity as well as beneficial bacteria such as Ruminococcaceae _UCG-014 and Lachnospiraceae _NK4A136. In parallel, we assessed if the adjuvant of SeDD98 with CsA had an impact on CsA-induced kidney injury which represents one of the major side effects. We found that SeDD98 significantly improved CsA nephrotoxicity in UC mice. We then validated this observation using chronic kidney disease (CKD) mice induced by CsA administration. These results demonstrated that SeDD98 in combination with CsA was associated with increased efficacy and reduced nephrotoxicity altogether, providing the scientific basis for the adjuvant therapy of probiotics in UC. [Display omitted] [ABSTRACT FROM AUTHOR]

• Solubility study of mesalazine in ternary mixture of ethanol, propylene glycol, and water at different temperatures. • Correlation/back-calculation of the solubility data by some mathematical models. • Calculation of thermodynamic parameters by using the van't Hoff and Gibbs equations. Mesalazine is a low-permeable and low-soluble drug, which makes it a class IV drug in the Biopharmaceutics Classification System. Hence, its solubilization can be helpful for various stages of formulation development. The purpose of this study was to investigate the solubilization manner and thermodynamics of mesalazine in ternary solvent combinations of {ethanol (1) + propylene glycol (2) + water (3)} using the shake-flask technique at (298.2–313.2) K. In the following, the mathematical representation of the acquired solubility data using some popular models was evaluated. The accuracies of the applied models were described by percentages of mean relative deviation (MRD%). Based on obtained results (MRD % < 10.0), it can be concluded that the trained models can adequately predict the solubility of mesalazine in the investigated ternary solvent combinations. The findings also revealed that the solution composition and temperatures greatly influence the solubility of mesalazine. In addition, the thermodynamic characteristics of the mesalazine dissolution process indicate that the mesalazine dissolution process is endothermic and entropy-driven. The generating data in the current work also expands the available solubility database for mesalazine in the solvent mixtures. [ABSTRACT FROM AUTHOR]

Myocarditis is a rare extra-intestinal complication of inflammatory bowel disease (IBD), in particular, ulcerative colitis. We report a case of acute myocarditis as first manifestation of severe ulcerative colitis. A 22-year-old man was admitted with fever, bloody diarrhea, and fatigue. He had suffered from frequent bloody diarrhea, abdominal pain, fatigue, and weight loss for one month. A 12-lead-electrocardiogram showed sinus rhythm with QRS fragmentation and T waves inversion. High sensitivity troponin-I was elevated and the echocardiogram showed a mild pericardial effusion and inferior hypokinesia with normal ejection fraction. Cardiac magnetic resonance disclosed late enhancement in the inferior wall, corroborating the hypothesis of myocarditis. One week later, a colonoscopy revealed severe ulcerative extensive colitis (Mayo subscore 3). 5-aminosalicylic acid (mesalazine) and systemic steroid were started with good clinical and biochemical response. The following days the patient developed mesalazine hepatic and pancreatic induced toxicity requiring drug discontinuation and strict multi-disciplinary follow-up. At 7 months follow-up intestinal symptoms were well controlled with complete normalization of liver and pancreatic enzymes. Transthoracic echocardiography showed normal biventricular function and pericardial effusion resolution. This case underscores the importance of a high suspicion for extra intestinal involvement in patients with IBD. These complications may be multifactorial and need multidisciplinary management. • When a patient was first-time diagnosed with a severe form of inflammatory bowel disease or has a disease relapse, bear in mind myocarditis as possible extra intestinal manifestation. • Multidisciplinary management is crucial to ensure the best level of care and follow-up in a such challenging and insidious clinical picture. [ABSTRACT FROM AUTHOR]

An anti-inflammatory medication termed Mesalazine (MLZ) is generally recommended to prevent inflammatory bowel diseases (IBD). However, its prolonged usage has been associated with the risk of kidney failure. Therefore, there is a pressing need for the development of effective electrocatalysts to enable rapid detection of MLZ in the environment. Layered double hydroxides (LDHs) have emerged as promising candidates in the realm of sensor technology due to their adjustable interlayer spacing and large surface area. In this study, we utilized the hydrothermal method to synthesize cobalt aluminum-layered double hydroxide (CoAl-LDH) and evaluated its suitability as an active electrocatalyst for MLZ detection. The prepared CoAl-LDH was characterized for its physicochemical attributes employing XRD, FT-IR, XPS, FESEM, and TEM analysis. Subsequent examination of its electrochemical properties via voltammetric techniques revealed that the CoAl-LDH-modified glassy carbon electrode (GCE) exhibited enhanced electrocatalytic activity. Notably, the CoAl-LDH/GCE demonstrated a lower detection limit of 0.029 µM and a linear detection range spanning from 0.049 to 665.1 µM. Furthermore, the modified electrode demonstrated favorable attributes such as good repeatability, reproducibility, and stability. Real-time application of the modified electrode in the spiked water and urine samples yielded satisfactory recovery results, indicating its potential for practical use in environmental monitoring. [Display omitted] • Facile synthesis of CoAl-LDH via hydrothermal approach. • Fabrication of CoAl-LDH/GCE sensor for the detection of mesalazine. • The sensor displays good selectivity, repeatability, and reproducibility. • The proposed sensor was used to detect mesalazine in real samples and obtained acceptable results. [ABSTRACT FROM AUTHOR]

[Display omitted] • Aminosalicylates are the most common drugs administered to inflammatory bowel disease patients. • Oral 5-aminosalicylic acid formulations are prescribed more often than topical formulations, despite having a lower efficacy. • pH-triggered drug delivery systems are the most effective approach for colon-targeted release. • Nanoparticles present a promising approach for Crohn's disease therapy due to selective uptake by inflamed tissue. Inflammatory bowel disease incidence has been constantly rising for the past few decades. Current therapies attempt to mitigate its symptoms since no cure is established. The most commonly prescribed drug for these patients is 5-aminosalicylic acid (5-ASA). Due to the low rate and seriousness of side effects compared to other therapies, 5-ASA is still largely prescribed in many stages of inflammatory bowel disease, including scenarios where evidence suggests low effectiveness. Although commercialized formulations have come a long way in improving pharmacokinetics, it is still necessary to design and develop novel delivery systems capable of increasing effectiveness at different stages of the disease. In particular, micro- and nano-sized particles might be the key to its success in Crohn's disease and in more serious disease stages. This review provides an overview on the clinical significance of 5-ASA formulations, its limitations, challenges, and the most recent micro- and nanoparticle delivery systems being designed for its controlled release. Emergent alternatives for 5-ASA are also discussed, as well as the future prospects for its application in inflammatory bowel disease therapies. [ABSTRACT FROM AUTHOR]

Drug-induced acute pancreatitis (DIAP) is an often-neglected entity where the disorder is the consequence of the toxic effects of various agents applied to treat potentially life-threatening conditions, such as inflammatory bowel disease. Here, we present the case of a male patient with ulcerative colitis with a history of two episodes of recurrent acute pancreatitis. After excluding other potential causes, we suspected DIAP since the patient received 5-aminosalycilate (5-ASA) prior to the first episode and, one year later, azathioprine (AZA) prior to the second episode. The causative effect of AZA was confirmed by performing a re-challenge with a reduced dose. While both episodes of DIAP had a mild disease course, they were associated with acute relapse of ulcerative colitis. Last seen, the patient was asymptomatic. With this case, we would like to highlight the importance and diagnostic difficulties of DIAP in the background of recurrent cases when common etiological factors of acute pancreatitis are excluded. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Mesalazine was efficiently encapsulated in chitosan microparticles. • The microsystems are characterized by significant bio-adhesion. • The formulation promoted significant anti-inflammatory activity. • Microencapsulated mesalazine may be used for the treatment of IBDs. Abstract The development of innovative strategies for the efficacious treatment of inflammatory bowel diseases (IBD) still remains a goal for pharmaceutical research. Targeting the lower section of the intestine is the main aim of therapy because it is the compartment primarily affected by IBDs. Mesalazine was microencapsulated in chitosan particles in order to modulate its unfavorable pharmacokinetic profile exploiting the bioadhesive feature of the polysaccharide and increase the anti-inflammatory effect of the drug following its rectal administration in an in vivo model of induced IBD. The chitosan microparticles (1–4 μm mean size) allowed efficient retention of the mesalazine and a prolonged drug release lasting up to 48 h. In vitro and in vivo experiments confirmed the significant mucoadhesion feature of the formulation by means of mucin assay and CLSM experiments and demonstrated its therapeutic efficacy at a drug concentration 2-fold lower than the commercial formulation Asamax® (13 mg/kg vs 26 mg/kg). [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Carbopol® 971 and poly(2-ethyl-2-oxazoline) form hydrogen-bonded interpolymer complexes in aqueous solutions and their complexation is strongly dependent on solution pH. This work investigated the complexation between these polymers in aqueous solutions. The compositions of interpolymer complexes as well as the critical pH values of complexation were determined. The structure of these complexes was studied in solutions using transmission electron microscopy and in solid state using elemental analysis, FTIR spectroscopy and differential scanning calorimetry. Solid compacts were prepared based on interpolymer complexes and physical blends of these polymers and their swelling behaviour was studied in aqueous solutions mimicking the fluids present in the gastrointestinal tract. These materials were used to prepare oral formulations of mesalazine and its release from solid matrices was studied in vitro. It was demonstrated that the complexation between Carbopol® 971 and poly(2-ethyl-2-oxazoline) has a profound effect on the drug release from matrix tablets. [ABSTRACT FROM AUTHOR]

Abstract Background Although very common in Western countries, poor epidemiological data on diverticular disease (DD) is available from the family practice. Aims To evaluate the behavior of Italian General Practitioners (GPs) on approaching DD. Methods Health Search Database was analyzed retrospectively. Results On a population of 975,523 individuals, 33,597 patients had a registered diagnosis of DD ("lifetime" prevalence = 3.4%, M = 3.2%, F = 3.7%; higher values are found in females over-65 years old; low rates of complications: diverticulitis = 0.3%, bleeding = 0.002%). As risk factors, NSAIDs and ASA were taken by 14.8% and 26.5% respectively, opioids by 7.5%, corticosteroids by 5.2%; as protective factors, 30.4% were under statins and 17.7% under calcium-antagonists. Approximately 13% of patients were referred to specialists. Colonoscopy and abdominal CT were prescribed to 48.5% and to 13% of already diagnosed patients. Among DD sufferers, 27% experienced hospitalization, but only 3.4% of cases were for a DD-linked problem. Treatment included rifaximin (61%), mesalazine (14.7%), probiotics (12.4%), ciprofloxacin (7.6%). Conclusion DD has a large impact in general practice with a higher prevalence in the elderly. GPs are required to pay particular attention to risk factors both for disease development and for its complications in order to reduce the costs deriving from diagnostic procedures, referral and hospitalization. [ABSTRACT FROM AUTHOR]

Abstract The aim of this work is to produce calcium pectin-silica gel beads containing mesalazine as a drug model in order to control the drug release in the colon. The mesalazine loaded calcium pectin-silica gel beads were prepared using the ionotropic gelation method. Energy-dispersive X-ray analysis revealed that increasing the Na 2 SiO 3 concentration led to an increase of the silicon content on the surface and in the cross-sections of the beads. The addition of Na 2 SiO 3 to the gel formulations made from the duckweed callus culture pectin led to a decrease in the swelling degree that appeared to be related to the higher gel strength of these beads. The beads made from pectins of campion and duckweed callus cultures with adding of 22.2 mg/ml of Na 2 SiO 3 showed the lowest release of mesalazine in simulated gastric and intestinal fluids. An increase in the reaction time up to 60 min during incubation in the cross-linking solution of CaCl 2 led to a slower release of drug from the beads. An elevated release of mesalazine was achieved in the simulated colonic fluid. Prepared calcium pectin-silica gel beads containing mesalazine as a drug model can be proposed for controlled drug release in the colon. Highlights • The mesalazine loaded pectin-silicate gel beads were prepared using the ionotropic gelation method. • The pectin-silicate gel beads made from the duckweed callus culture pectin had the higher gel strength. • The pectin-silicate gel beads with the higher content of silicon showed the lowest release of mesalazine. • An elevated drug release from pectin-silicate gel beads was achieved in the simulated colonic media. [ABSTRACT FROM AUTHOR]

• The Co-Mordenite/Mesoporous Carbon modified Glassy Carbon Electrode (Co-MOR/MC-GCE) was presented. • The voltammetric method for the ultrasensitive determination of mesalazine (MES) was developed. • The nanomolar level of LOD was achieved without any preconcentration step. • The method was applied for the determination of MES in pharmaceutical, environmental, and biological samples. In this paper, an ultrasensitive and highly selective analytical method for the voltammetric determination of the anti-inflammatory drug mesalazine (MES) at the Co-exchanged mordenite/mesoporous carbon modified glassy carbon electrode (Co-MOR/MC-GCE) is presented. The combination of unique properties of zeolite and mesoporous carbon, affirmed by conducting morphology and textural parameters studies, resulted in the fabrication of the unique platform sensing, which exhibited a significant enhancement effect of MES oxidation peak current. In the voltammetric determination of mesalazine by the means of differential pulse voltammetry (DPV), univariate optimization stage of the instrumental parameters and the pH value of the supporting electrolyte was performed. In 0.04 mol L−1 Britton-Robinson buffer solution (pH 2.0), the oxidation peak of MES at 0.41 V vs. Ag | AgCl | 3 M KCl reference electrode revealed a linear response in the range of 0.99 – 99.01 µg L−1 (6.47·10−9 – 6.47·10−7 mol L−1) with the limit of detection (LOD) equal to 0.27 µg L−1 (1.76·10−9 mol L−1). The developed protocol was successfully applied for the direct determination of mesalazine in pharmaceuticals, environmental waters, and biological fluids (human urine and serum) with recovery of 103.4 – 119.3%. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aimed to develop a novel sustained release system for mesalazine (MSZ) by preparing hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex loaded chitosan (CS) nanoparticles (NPs). The HP-β-CD/MSZ complex was prepared at 1:1 stoichiometry and characterized by using various analysis techniques. The HP-β-CD/MSZ/CS NPs prepared under the optimum condition had a spherical shape (90±17 nm diameter), a narrow size distribution, and a high loading efficiency. Compared with free MSZ, the HP-β-CD/MSZ/CS NPs exhibited an obvious sustained release of MSZ. The activity of the NPs against a cytokine-triggered inflammatory response was evaluated in cytokine-stimulated HT-29 cell lines by monitoring key inflammatory mediators. The results revealed that compared with free MSZ, the NPs more strongly inhibited the production of NO, PGE 2 , and IL-8, indicating the NPs possibly had better anti-inflammatory effects. Therefore, the established HP-β-CD/MSZ/CS NPs may be a promising delivery system of MSZ. [ABSTRACT FROM AUTHOR]

[Display omitted] • Mesalazine hollow suppository (MHS) owns an inner spring and an outer curved shell. • M-MHS is assembled with an FDM 3D-printed spring and a molding shell. • Sustained drug release and long-term rectal retention of M-MHS in the rectum. • Highly efficient treatment of ulcerative colitis using M-MHS. Mesalazine (MSZ) suppositories are a first-line medication for the localized treatment of ulcerative colitis (UC). However, the frequent defecation of patients with UC influences the retention of the suppository in the rectum and multiple doses have to be applied. Here, a mesalazine hollow suppository (MHS) is developed using three-dimensional (3D) printing. The MHS is composed of an inner supporting spring and an outer MSZ-loaded curved hollow shell. Springs were prepared using fused deposition modeling (FDM) 3D printing with thermoplastic urethane filaments, followed by splitting. The optimal parameters, including elasticity, filament diameter, spring inner diameter, and filament distance, were screened. The shell was prepared by FDM 3D printing utilizing MSZ, polyvinyl alcohol, and polyethylene glycol, which were assembled with springs to obtain FDM 3D-printed MHS (F-MHS); if 3D-printed metal molding was used in preparing shell, mold-formed MHS (M-MHS) was obtained. The F-MHS exhibited faster MSZ release than the M-MHS; therefore, the molding method is preferable. The inserted M-MHS was retained in the rat rectum for 5 h without affecting defecation. M-MHS alleviated tissue damage of UC rats and reduced inflammation with low levels of myeloperoxidase and proinflammatory cytokines. Personalized MHS is a promising medication for the localized treatment of UC. [ABSTRACT FROM AUTHOR]

[Display omitted] • CoIII complexes have been designed for hypoxia-selective anticancer drug delivery. • Redox potential of CoIII-mesalazine complexes has been tuned by ancillary ligands. • Ascorbate successfully simulate biological redox activation. • O 2 -dependent dissociation of the mesalazine has been achieved upon Co3+/Co2+ reduction. Cobalt(III) complexes have been designed to coordinate and selectively deliver bioactive molecules to hypoxic regions of solid tumors. In this way, we report the synthesis, electrochemistry and spectroscopic properties and reactivity of three mesalazine-cobalt(III) complexes. An effect of the donor/acceptor capabilities of the ancillary ligands (py 2 en, me 2 py 2 en and tpa) was observed. Co3+/Co2+ potentials of all complexes are within the expected range for reduction/oxidation under biological conditions. An O 2 -dependent dissociation of mesalazine was observed for complexes 1 and 2 upon reduction by ascorbic acid. [ABSTRACT FROM AUTHOR]

This study's aim was to obtain composites from palygorskite (PLG) and chitosan (CS) in order to modify 5-aminosalicylic (5-ASA) release. Initially, the PLG:CS composite was obtained using glutaraldehyde (GLA) as a reticular agent. Then, PLG, CS and PLG:CS were characterized by means of analytical techniques such as CHN elemental analysis, surface area analysis, XRD, FTIR, DSC and TG, SEM, adsorption tests and release profiles. Based on analytical data, the formation of the PLG:CS composite which showed the presence about 19% of CS, decrease in specific surface area, morphological analysis modified, visible change of crystallinity, of FTIR and thermal analysis. In relation to the drug-composite interaction, PLG:CS exhibited a significant increase in adsorption with 5-ASA at 58.24% in relation to PLG and CS which were at 16.29% and 23.96% respectively. The release profiles show that the PLG:CS composite changed the 5-ASA release speed in analyzed simulated fluids (intestinal and stomach) unlike other systems. Thus, the PLG:CS composite with proven synergy of the PLG and CS inherent properties showing 5-ASA effective modified release. Hence, this composite has potential benefits for the vectorization of drugs. [ABSTRACT FROM AUTHOR]

The synthesis of pectin-silica gels for controlled drug release in gastrointestinal tract (GIT) using low methoxyl (LM) and high methoxy (HM) pectins and tetraethoxysilane (TEOS) as precursor is described. The FTIR spectra of the pectin-silica gels show intense absorption bands at 1246 cm −1 and 802 cm −1 corresponding to the vibrations C O Si bonds, which absent in the FTIR spectra of the native pectins that indicate the formation covalent bond between silica and pectin macromolecules in the pectin-silica gels. Pectin-TEOS, pectin-Ca-TEOS and pectin-TEOS-Ca beads with mesalazine are synthesized by different combinations of sol-gel method using TEOS and ionotropic gelation method using calcium chloride. The best resistant of pectin-TEOS and pectin-Ca-TEOS beads during incubation in simulated gastric fluid for 2 h and subsequently in simulated intestinal fluids for 18 h is indicated. Pectin-TEOS beads are characterized by higher encapsulation efficiency (to 28%) than pectin-Ca-TEOS beads (to 16%). The drug release of pectin-silica beads in simulated GIT occurs gradually up to 80% and is directly dependent on the hardness of the beads. The surface morphology of beads is shown. The use of pectin-silica beads is promising with regard to the development of controlled release of drug formulations. [ABSTRACT FROM AUTHOR]

A rapid analytical method without the time-consuming separation step was developed to simultaneously determine mesalazine and its N -acetylated metabolite. A simply designed electrochemical sensor with functionalized carbon nanotubes in a Nafion matrix was constructed for this purpose. The presence of the nanocomposite modifier on the electrode surface significantly affects the voltammetric response of target analytes. The morphology of the modified surface was investigated by scanning electron microscopy. The effect of modifier amount on the sensor performance was investigated in order to obtain the most favorable response of mesalazine since it was found in lower concentration limits in real samples then its metabolite due to the rapid drug elimination and the slightly slower renal metabolite excretion. Under optimal conditions, the anodic peak currents measured by square-wave voltammetry increased linearly after short accumulation of 30 s in the range of 5.0×10 −8 –2.5×10 −6 M and 1.0×10 −7 −5.0×10 −6 M for drug and metabolite, respectively. In addition to stable response, the sensor has excellent performance associated with high sensitivity (2.33×10 7 and 8.37×10 6 µA M −1 for drug and metabolite, respectively). The synergistic effect of the carbon nanotubes and Nafion polymer film yielded detection limit of 1.2×10 −8 M for mesalazine and 2.6×10 −8 M for its metabolite that is comparable to known chromatographic methods. Due to the easy preparation and regeneration, the proposed sensor opens new opportunity for fast, simple and sensitive analysis of drug and its metabolite in human serum samples as well as direct quantification of mesalazine in delayed-release formulations. [ABSTRACT FROM AUTHOR]

Olsalazine sodium, salicylate derivative (prodrug) is effectively bioconverted to mesalazine (5-aminosalicylic acid; 5-ASA), which has an anti-inflammatory activity in ulcerative colitis. In this article, a novel highly sensitive and selective method was developed and validated to determine mesalazine in human plasma using a derivatization technique to enhance the signal intensity by using ultra- high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC–MS/MS) with an electrospray ionization interface. The sample preparation consisted of a derivatization with propionyl anhydride followed by liquid liquid extraction (LLE) to remove the interference and minimize the matrix effect of human plasma. The multiple reaction monitoring (MRM) mode of the negative ion was performed and the transitions of m / z 208.1 → 107.0 and m / z 211.1 → 110.1 were used to measure the derivative of mesalazine and mesalazine- d 3 . The chromatographic separation was achieved using kinetex XB-C18 (100 × 4.6 mm 2.6 μ) analytical column with 0.1% formic acid in water and acetonitrile as mobile phase with a gradient elution. Nominal retention times of mesalazine and IS were 3.08 and 3.07 min, respectively. Absolute recovery was found to be between 82–95% for analyte and about 78% for IS. The standard curves was linear ( r 2 > 0.995) in the concentration range 0.10 to 12.0 ng/mL with lower limit of quantification (LLOQ) in human plasma was 0.10 ng/mL. The average intra-day/inter-day precision values (%CV) were in the range from 0.6–2.9 % and 1.3–3.8 %, respectively, while the average accuracy value was 103.8–107.2%. This method has been successfully applied to the human pharmacokinetics of olsalazine sodium 250 mg capsules following single oral administration. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fabrication of polymerized-congo red modified electrode for mesalazine (MSZ) sensing. • The simultaneous study was conducted for the binary mixture of MSZ and FA. • The determination of MSZ in pharmaceutical formulations reveals an acceptable recovery. • A simple and sensitive sensing platform was shown. Here in, a sensitive and simple methodology for the detection of mesalazine (MSZ) was reported at polymerized-congo red modified carbon paste working electrode (PCR-CPE) at physiological pH. The PCR-CPE exhibited a good electrochemical sensing behaviour towards the detection of MSZ, even in the presence of interferons. Under an optimal experimental environment, the electrochemical response to MSZ was almost linear in the given concentration range (80 µM–200 µM) with a detection limit of 1.12 × 10–7 M. The sensitivity, long-term stability, reproducibility was showed by the modified electrode. Moreover, the PCR-CPE showed good analytical signal to detect the folic acid (FA) as well. [ABSTRACT FROM AUTHOR]

The electro analytical determination of Mesalazine (MSZ) and Folic acid (FA) were done using a murexide-based sensor developed on a glassy carbon electrode. Electro oxidations for MSZ and FA were investigated in buffer (PBS) of pH 7.4 using cyclic voltammetry. This work was carried out to study the effect of change in the concentration of MSZ, scan rate, and pH of the electrochemical behaviour of MSZ on poly-murexide modified glassy carbon electrode [poly(MX) MGCE] surface. The limit of detection of MSZ was found to be 9.1 × 10−5 M in the linear concentration range of 2.5 × 10−4M to 12.5 × 10−4M. The modified electrode has also shown good sensitivity for detection of FA and simultaneous detection of MSZ and FA. The two distinct individual peaks at the corresponding peak potentials of MSZ and FA were obtained. The poly (MX) MGCE electrode showed a stable, reproducible, and sensitive result for MSZ and FA. [Display omitted] • Demonstration of a simple method for the modification of glassy carbon electrode. • The fabricated electrode was used for the electrochemical determination of mesalazine (MSZ) and folic acid (FA). • The simultaneous determination of MSZ and folic acid by CV technique. • The lower limit of detection was achieved. [ABSTRACT FROM AUTHOR]

[Display omitted] • A microfluidic device can be used for the extraction of mesalazine. • The procedure, which is used only for acidic or basic compounds, is successfully used for a zwitterion compound with three dissociation constants. • The developed system is successfully applied in urine and blood samples with extraction efficiencies over 88% For the first time, a microfluidic device-based liquid phase microextraction followed by HPLC-UV analysis was introduced and optimized by response surface methodology (RSM) for the extraction and determination of mesalazine. Two symmetrical micro-channels separated by a support liquid membrane formed the microfluidic chip for passive diffusion of the target from the donor phase to the acceptor phase. The effects of the main variables, including the flow rate, pH of donor and acceptor phases, and solvent type, as well as their interactions were investigated on the extraction efficiency of the mesalazine and optimized by the D-optimal experimental design. The predicted extraction efficiency percentage of mesalazine at the optimal conditions (flow rate, 0.0197 mL/min; donor phase pH, 5.4; acceptor phase pH, 11.9; and solvent, 1-Butanol) was 100% and confirmed by its experimental value with an error of 0.1%. In addition, the procedure provided an acceptable repeatability with relative standard deviations lower than 2%, a detection limit of 0.81 ng/mL, and a quantitation limit of 2.7 ng/mL. This microfluidic chip was successfully applied for the determination of mesalazine in human plasma and urine samples with extraction efficiencies within the range of 88–92%. The proposed method provides advantages such as reduced sample consumption and extraction time, low cost, portability, and high extraction efficiency compared to the existing sample preparation techniques for mesalazine. [ABSTRACT FROM AUTHOR]

Background Mesalazine is used as maintenance therapy in ulcerative colitis but the optimal dosage is still controversial. Aim To compare the remission-maintenance efficacy and tolerability of two daily doses of oral mesalazine (4.8 g and 2.4 g) in patients with ulcerative colitis with frequent relapses in a randomized controlled trial. Methods 112 ulcerative colitis patients in remission were enrolled and randomly allocated to treatment for 1 year with oral mesalazine at a daily dose of 4.8 g ( n = 56, Group A) or 2.4 g ( n = 56, Group B). Results At the end of the 12 months, intention to treat analysis revealed persistent remission in 42 (75%) in Group A and 36 (64.2%) in Group B ( p = 0.3). The higher daily dose (4.8 g) proved to be significantly more effective for maintaining remission in patients under 40 years of age (90.5% Group A vs. 50% Group B; Fisher's exact test, p = 0.0095) and in those with extensive disease (90.9% Group A vs. 46.7% Group B; Fisher's exact test, p = 0.0064). Conclusions In ulcerative colitis patients younger than 40 years and/or with extensive disease, a daily dose of 4.8 g oral mesalazine results in increased rates and duration of remission compared to 2.4 g. [ABSTRACT FROM AUTHOR]

Novel, mesalazine, metronidazole conjugates 6a – e with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates exhibit comparable anti-inflammatory activity with parent drugs and (b) the potent bis-conjugates show no visible stomach lesions. 3D-pharmacophore and 2D-QSAR modeling support the observed bio-properties. [ABSTRACT FROM AUTHOR]

• General cosolvency models for prediction of mesalazine solubility in binary systems. • Combination of Abraham solvation parameters with proposed general models. • Combination of Hansen solubility parameters with proposed general models. • Using KAT-LSER model for representation of mesalazine solubility data at 298.2 K. The present study aims are to develop general models based on Abraham solvation parameters and Hansen solubility parameters to predict mesalazine solubility in cosolvency systems at different temperatures. The Jouyban-Acree model as an accurate mathematical model is combined with physicochemical parameters of the Abraham solvation parameters and the Hansen solubility parameters to achieve the predictive cosolvency models. KAT-LSER model was also applied for the representation of mesalazine solubility data at 298.2 K. The applicability of the proposed methods was evaluated by calculating the overall mean relative deviations (MRDs %) values of the solubility data for mesalazine in 11 cosolvency systems and discussed. The trained models present a good estimation of the solubility behavior of mesalazine in various cosolvency systems, including aqueous and non-aqueous mixtures. The essential information presented by these models can be used in different stages of new drug and drug candidate discovery, development, and industrial procedures, so that they permit the scientist the choice the best solvent system for mesalazine with considering the fact that some solvents such as ethanol, propylene glycol, polyethylene glycols, N-methyl pyrrolidone, and carbitol are commonly used solvents in drug preparation procedure and other organic and volatile solvents are used in the extraction and purification step. [ABSTRACT FROM AUTHOR]

[Display omitted] The aim of the present study was to investigate the effect of coadministration of the proton pump inhibitor (PPI) esomeprazole on the upper GI tract behavior and systemic exposure of mesalazine from two mechanistically different colon targeted delivery systems: Claversal (pH-dependent release) and Pentasa (prolonged release). To this end, gastric, jejunal and systemic concentrations of mesalazine and its metabolite N-acetyl mesalazine were monitored in 5 healthy volunteers following oral intake of Pentasa or Claversal with or without PPI pre-treatment (cross-over study). Our exploratory study demonstrated that pre-treatment with a PPI may affect the release and absorption of mesalazine from formulations with different modified release mechanisms. Upon intake of Claversal, the onset of mesalazine absorption was accelerated substantially by PPI pre-treatment. While the PPI-induced increase in pH initiated the disintegration process already in the upper GI tract, the release of mesalazine started beyond the proximal jejunum. Upon intake of Pentasa, PPI pre-treatment seemed to increase the systemic exposure, even though the underlying mechanism could not be revealed yet. The faster release of mesalazine in the GI tract and/or the increased systemic absorption following PPI pre-treatment may reduce the ability of mesalazine to reach the colon. Future research assessing mesalazine disposition in the lower GI tract is warranted. [ABSTRACT FROM AUTHOR]

The in vivo proof of concept of a novel double-coating system, based on enteric polymers, which accelerated drug release in the ileo-colonic region, was investigated in humans. Prednisolone tablets were coated with a double-coating formulation by applying an inner layer composed of EUDRAGIT® S neutralised to pH 8.0 and a buffer salt (10% KH2PO4), which was overcoated with layer of standard EUDRAGIT® S organic solution. For comparison, a single coating system was produced by applying the same amount of EUDRAGIT® S organic solution on the tablet cores. Dissolution tests on the tablets were carried out using USP II apparatus in 0.1N HCl for 2h and subsequently in pH 7.4 Krebs bicarbonate buffer. For comparison, tablets were also tested under the USP method established for modified release mesalamine formulations. Ten fasted volunteers received the double-coated and single-coated tablets in a two-way crossover study. The formulations were radiolabelled and followed by gamma scintigraphy; the disintegration times and positions were recorded. There was no drug release from the single-coated or double-coated tablets in 0.1N HCl for 2h. The single-coated tablets showed slow release in subsequent Krebs bicarbonate buffer with a lag time of 120min, while in contrast drug release from the double-coated tablets was initiated at 60min. In contrast, using the USP dissolution method, normally employed for modified release mesalamine products, no discrimination was attained. The in vivo disintegration of the single-coated EUDRAGIT® S tablets in the large intestine was erratic. Furthermore, in 2 volunteers, the single-coated tablet was voided intact. Double-coated tablets disintegrated in a more consistent way, mainly in the ileo-caecal junction or terminal ileum. The accelerated in vivo disintegration of the double-coating EUDRAGIT® S system can overcome the limitations of conventional enteric coatings targeting the colon and avoid the pass-through of intact tablets. Moreover, Krebs bicarbonate buffer has the ability to discriminate between formulations designed to target the ileo-colonic region. [ABSTRACT FROM AUTHOR]

Abstract: This study has performed on electromembrane extraction (EME) of some zwitterionic compounds based on their acidic and basic properties. High performance liquid chromatography (HPLC) equipped with UV detection was used for determination of model compounds. Cetirizine (CTZ) and mesalazine (MS) were chosen as model compounds, and each of them was extracted from acidic (as a cation) and basic (as an anion) sample solutions, separately. 1-Octanol and 2-nitrophenyl octylether (NPOE) were used as the common supported liquid membrane (SLM) solvents. EME parameters, such as extraction time, extraction voltage and pH of donor and acceptor solutions were studied in details for cationic and anionic forms of each model compound and obtained results for two ionic forms (cationic and anionic) of each compound were compared together. Results showed that zwitterionic compounds could be extracted in both cationic and anionic forms. Moreover, it was found that the extraction of anionic form of each model compound could be done in low voltages when 1-octanol was used as the SLM solvent. Results showed that charge type was not highly effective on the extraction efficiency of model compounds whereas the position of charge within the molecule was the key parameter. In optimized conditions, enrichment factors (EF) of 27–60 that corresponded to recoveries ranging from 39 to 86% were achieved. [Copyright &y& Elsevier]

Abstract: The goal was to make available a delayed-release dosage form of mesalazine to be dispersed in water to facilitate swallowing in adults and children. Mesalazine microparticles containing carnauba wax were prepared by spray-congealing technique. A second step of spray-congealing of carnauba microparticles dispersed in liquefied stearic acid gave rise to mesalazine lipid microcapsules in which several carnauba microparticles remained embedded as cores in a reservoir structure. In order to favor their water dispersion, the lipid microcapsules were dry coated by tumbling them with different ratios of mannitol/lecithin microparticles prepared by spray-drying. Release rate measurements showed a delayed-release behavior, in particular a pH-dependence with less than 10% of drug released in acidic medium and complete release in phosphate buffer pH 7.4 in 4–5h. The layering with hydrophilic excipient microparticles allowed manufacturing of a pH-dependent dosage form suitable for extemporaneous oral use in adults and children. [Copyright &y& Elsevier]

Abstract: An HPLC method for the quantitative analysis of mebeverine HCl, 5-aminosalicylic acid (5-ASA), sulphasalazine and dispersible aspirin has been developed and then applied to these specific medicines when stored, with other medications, in Venalink blister packs (monitored dosage system) for periods of up to 35 days. Chromatographic separation was achieved on a reversed-phase C12 column with an isocratic mixture of methanol, water and acetic acid as the mobile phase. The method was validated regarding: accuracy, precision, detection limits, quantification limits, specificity and robustness. [Copyright &y& Elsevier]

Abstract: Bicarbonate media are reflective of the ionic composition and buffer capacity of small intestinal luminal fluids. Here we investigate methods to stabilise bicarbonate buffers which can be readily applied to USP-II dissolution apparatus. The in vitro drug release behaviour of three enteric coated mesalazine (mesalamine) products is investigated. Asacol® 400mg and Asacol® 800mg (Asacol® HD) and the new generation, high dose (1200mg) delayed and sustained release formulation, Mezavant® (Lialda®), are compared in pH 7.4 Krebs bicarbonate and phosphate buffers. Bicarbonate stabilisation was achieved by: continuous sparging of the medium with 5% CO2(g), application of a layer of liquid paraffin above the medium, or a specially designed in-house seal device that prevents CO2(g) loss. Each of the products displayed a delayed onset of drug release in physiological bicarbonate media compared to phosphate buffer. Moreover, Mezavant® displayed a zero-order, sustained release profile in phosphate buffer; in bicarbonate media, however, this slow drug release was no longer apparent and a profile similar to that of Asacol® 400mg was observed. These similar release patterns of Asacol® 400mg and Mezavant® displayed in bicarbonate media are in agreement with their pharmacokinetic profiles in humans. Bicarbonate media provide a better prediction of the in vivo behaviour of the mesalazine preparations investigated. [Copyright &y& Elsevier]

Abstract: There is epidemiological evidence, that mesalazine can inhibit colon cancer development by affecting proliferation and apoptosis. Several studies suggest that supplementary intake of butyrate may yield to improved efficacy of mesalazine. However, the underlying molecular mechanisms of such interaction remain unknown. This study addressed the combinatory effect of both substances on the growth of Caco-2 cells. Challenging of cells with mesalazine and butyrate provoked a time-dependent decrease in both cell counts and proliferation. Co-treatment with the substances could further intensify these effects. The growth-inhibitory action of mesalazine and butyrate was accompanied by a significant increase in caspase-3 activity, cleavage of PARP and caspase-8, while decreasing the expression of Xiap and Survivin simultaneously. Co-incubation of both substances exaggerated effects on all examined apoptosis-regulatory proteins except for Xiap. Our data demonstrate that co-treatment of mesalazine and butyrate evoked additive effects on inhibition of cell growth and induction of apoptosis in Caco-2 cells. [Copyright &y& Elsevier]

Abstract: A 50-year-old male patient treated with mesalazine for Crohn’s disease was admitted in our unit for a chest pain, associated with nonspecific ST depression or ECG and troponine elevation. Coronarography showed minimal changes while SPECT imagery suggested a posterobasal subendocardial infarction, so that the diagnosis was unclear between ischemic disease and mesalazine-induced myocarditis. Eventually, MRI demonstrated clearly a subendocardial posterior infarction eliciting the diagnosis of mesalazine-induced myocarditis. This case report illustrates, in our opinion, that MRI is of invaluable interest in evaluating the characteristics of myocardium, and must be the cornerstone in the diagnosis of myocardial diseases. [Copyright &y& Elsevier]

Abstract: A new HPLC method for the determination of 5-aminosalicylic acid (5-ASA) and N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) in human plasma was developed and validated. Plasma samples were analyzed after protein precipitation with methanol and the two analytes were separated using a C18 column with a mobile phase composed of 17.5mmol/L acetic acid (pH 3.3):acetonitrile=85:15 (v/v) at 0.2mL/min flow rate. 4-ASA and N-Ac-4-ASA were used as internal standards. Selective detection was performed by tandem mass spectrometry with electrospray source, operating in negative ionization mode and in multiple reaction monitoring acquisition (m/z 152→108 for 5-ASA; m/z 194→150 and 194→107 for N-Ac-5-ASA). The limit of quantification (LOQ) was 50ng/mL for both analytes (0.2ng injected) and matrix-matched standard curves showed linearity up to 4000ng/mL. In the entire analytical range the within- and between-batch precision (R.S.D.%) values were respectively ≤6.3% and ≤11% for 5-ASA and ≤8.0% and ≤10% for N-Ac-5-ASA. For both analytes the within- and between-batch accuracy (bias%) values ranged respectively from −8.4% to 7.9% and from −7.9% to 8.0%. The overall recoveries (n =6) at three tested concentration levels (i.e. 100, 1000 and 4000ng/mL) were respectively >90% for 5-ASA and >95% for N-Ac-5-ASA (R.S.D.%≤10%). The method was applied to evaluate the pharmacokinetic of 5-ASA after a single oral dose administration of this compound (1200mg) to 24 healthy volunteers. The mean maximum concentration levels were 680ng/mL for 5-ASA and 1240ng/mL for N-Ac-5-ASA and the kinetic profiles were in agreement with previous studies. [Copyright &y& Elsevier]

Abstract: Background and aims: Increased epithelial cell proliferation may be detected in diverticular disease, but antibiotics have failed in reducing it. We assess therefore the effect of mesalazine on epithelial cell proliferation in diverticular disease. Methods: A prospective study was conducted on 20 consecutive patients with a new endoscopic diagnosis of symptomatic uncomplicated diverticular disease. The patients were treated with mesalazine 1.6mg/day for 1 year. The Ki-67 antigen index of the whole crypt and in the upper third was separately evaluated before and after starting the treatment. Results: Cell proliferation index was higher in diverticular disease patients than healthy controls both in the whole crypt (median 6.7%, range 2–9% vs. median 1.6%, range 1–3%, p =0.001) and in the upper third of the crypt (median 6.8%, range 2–8% vs. median 1.8%, range 1–3%, p =0.001). Cell proliferation decreased throughout the follow-up. In the whole crypt it was 6.7% at entry and 3.8% at the end of treatment (p <0.005), whereas it was 6.8% at entry and 2.9% at the end of treatment in the upper third of the crypt (p <0.005). Conclusions: We found mesalazine effective in reducing the colonic cell proliferation in long-term treatment for colonic diverticular disease. [Copyright &y& Elsevier]

Delayed release dosage forms such as Asacol® employ coatings that are engineered to breakdown and release the drug topically at the nominal pH of the lower intestinal tract. Asacol tablets were found to dissolve in an erratic fashion when they are dissolved in buffers below pH 7 which can occur naturally. In this study Terahertz pulsed imaging (TPI) was used to accurately map the coating thickness of a group of Asacol tablets that were subsequently dissolved using the USP method at pH 6.8. The mean dissolution times were found to correlate with the average coating thickness measured over all surfaces. Thickness values for a single randomly selected face did not correlate well with the dissolution results. The speed and ease of TPI mapping may make it an attractive replacement for wet dissolution testing both in product development and eventually for process analysis. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1543–1550, 2008 [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to develop the alginate based mesalazine tablets for intestinal delivery. Sodium alginate is a biocompatible, natural polymer with pH-sensitive gel-forming ability. Matrix tablets were prepared with two types of sodium alginate of different amounts. The in vitro release characteristics of mesalazine from alginate tablets were compared with those of the commercial product (Salofalk®). X-ray imaging was used to monitor the tablets throughout the gastrointestinal system. Although alginate tablets gave a faster release in an acidic medium compared with the commercial product (Salofalk®), the cumulative amount of released drug of the optimum formulation was found to be almost the same as that of the commercial product at the end of 4h. The alginate type and amount in the matrices played an important role in basic media. The release of the optimum formulation containing low viscosity alginate was found to be almost identical to that of the commercial product in acidic and basic media. Tablets were visualized to determine whether they were located in the terminal ileum or cecum for 3–6h. Mesalazine-alginate matrix tablet formulations can deliver the drug to the small and large intestine. Thus, the alginate matrix system may be a promising system for the treatment of Crohn’s disease involving both the ileum and large intestine. [Copyright &y& Elsevier]

Abstract: Background: Topical beclomethasone diproprionate has shown efficacy in ulcerative colitis. Aim: To assess, in a multicenter, randomized, double-blind study, the tolerability and safety of topical beclomethasone diproprionate (3mg) enema and foam versus mesalazine (2g) enema and foam in mild–moderate distal ulcerative colitis. Patients: In 15 referral gastrointestinal units, 99 patients with distal ulcerative colitis were enrolled. This number was lower than planned according to the statistical analysis, due to a low recruitment rate. Methods: Patients were randomly assigned to random preparations (beclomethasone diproprionate enema, beclomethasone diproprionate foam, mesalazine enema, mesalazine foam) once nightly for 8 weeks, with clinical and endoscopical assessment (Disease Activity Index score) at baseline (T0), 4 (T4) and 8 weeks (T8). Results were expressed as median and range (95% confidence interval). The efficacy was assessed by comparing the Disease Activity Index value at T4 and T8 by using the Student''s t-test or the Wilcoxon–Mann–Whitney test. Results: Efficacy was comparable in the beclomethasone diproprionate or mesalazine groups at both T4 and T8 (response at T4: beclomethasone diproprionate 78% [95% confidence interval 0.6–0.8] versus mesalazine 79% [95% confidence interval 0.6–0.8]; T8: beclomethasone diproprionate 84% [95% confidence interval 0.7–0.9] versus mesalazine 90% [95% confidence interval 0.7–1.0]; p =n.s.; remission at T4: beclomethasone diproprionate 24% [95% confidence interval 0.1–0.3] versus mesalazine 28% [95% confidence interval 0.1–0.3]; remission at T8: beclomethasone diproprionate 36% [95% confidence interval 0.2–0.5] versus mesalazine 52% [95% confidence interval 0.3–0.6]; p =n.s.).The Disease Activity Index lowered at T4 and T8 versus T0 in the four groups (T4 versus T0: beclomethasone diproprionate foam Disease Activity Index 2 versus 6 p <0.0001; beclomethasone diproprionate enema 4 versus 6, mesalazine enema 3 versus 6, mesalazine foam 3.5 versus 7, p <0.001 for all three groups; T8 versus T0: p <0.01). The Disease Activity Index lowered at T8 versus T4 in the beclomethasone diproprionate enema and foam (Disease Activity Index: 2 versus 4 and 1 versus 4, respectively; p <0.05) and in the mesalazine enema (Disease Activity Index: 1.5, range 0–4 versus 3, range 0–12; p <0.01), but not in the mesalazine foam group (Disease Activity Index: 1, range 0–9 versus 3.5, range 0–8; p =n.s.). The safety profile was favourable for all groups. Conclusions: Beclomethasone diproprionate and mesalazine enema and foam show a comparable tolerability and efficacy in mild active distal ulcerative colitis. [Copyright &y& Elsevier]

Abstract: Mesalazine (5-ASA) is a compound being used in the therapy of inflammatory bowel disease (IBD). Considering the fact that 5-ASA is locally active and that the location of inflammation in IBD may vary, it is recognized that the release profile of 5-ASA drugs is the dominant factor for adequate local bioavailability. Furthermore, it is hypothesized that systemic absorption of 5-ASA (mainly in the upper intestinal segments) increases the risk of side effects. These facts relate to the conclusion that a method determining the dissolution profile under biorelevant conditions is a valuable tool for evaluation and comparison of 5-ASA-products. We tested several commercially available products (Salofalk® tablets, Salofalk® granules, Asacol® tablets, Pentasa® tablets and granules) in a gastro-intestinal simulation system (GISS). The GISS is based on the pharmacopeial dissolution test. The release profiles of all products are in agreement with their technological concepts. The percentage of the dose released in the simulated colon is small in all products. The GISS is a robust system able to discriminate between products which apply different modified-release technologies. Colon-selectivity of modified-release 5-ASA products might further be improved. The commercially available 5-ASA containing oral dosage forms exhibit different release profiles, which suggests that the optimal product may differ per patient. [Copyright &y& Elsevier]

Abstract: Patients with inflammatory bowel disease have a higher risk of developing colorectal cancer. The main risk factors for colorectal cancer are not suitable targets for therapeutic intervention, and primary chemoprevention is an intriguing therapeutic option. The analogies between acetyl-salycilic acid and 5-amino-salycilic acid, and the results obtained by using acetyl-salycilic acid as a chemopreventive agent in patients with sporadic colorectal cancer have prompted the study of potential chemopreventive effects of 5-amino-salycilic acid in inflammatory bowel disease. The results of both epidemiological and experimental studies have shown that long-term 5-amino-salycilic acid treatments appear to have a chemopreventive effect. The evidence for this effect is provided by retrospective and case-control studies whose results, however, do not reach the highest grades for evidence-based recommendations. Nevertheless, these results are supported by a series of experimental studies demonstrating the multiplicity of actions of 5-amino-salycilic acid. Although data regarding the chemopreventive effect of 5-amino-salycilic acid may not be rigorous enough to meet the criteria for the highest evidence-based medicine recommendations, we feel that the argument to wait until we have Grade A evidence is not necessarily rational in this case, because discontinuation of 5-amino-salycilic acid treatment to perform a randomised controlled trial would be unethical secondary to their proven efficacy for maintenance treatment. [Copyright &y& Elsevier]

Abstract: The bacterial substrate amorphous amylose, in the form of a film coating, provides a means of delivering drugs to the colon. This coating has traditionally been applied to multi-unit systems, in part because of the small size and divided nature of this type of dosage form, which provides a large surface area for enzymatic attack and drug release. The present study was conducted to explore the utility of the coating for colonic targeting of single unit tablet systems. Amylose was combined with the water-insoluble polymer ethylcellulose, which acts as a structuring agent, in different proportions to produce film coatings of various thicknesses for application to mesalazine (mesalamine or 5-aminosalicylic acid)-containing tablets. Drug release from the coated products was assessed under pH dissolution conditions resembling the stomach and small intestine, and also in conditions simulating the colon using a batch culture fermenter inoculated with human faecal bacteria. The rate and extent of drug release was related to the ratio of amylose to ethylcellulose in the film and the thickness of the coating. Increasing the proportion of ethylcellulose in the film and/or the thickness of the coating depressed the rate of drug release in the conditions of the upper gastrointestinal tract. Drug release from the coated products was accelerated in the fermentation environment of the colon. This is attributed to bacterial digestion of the amylose component of the film coat producing pores for drug diffusion. This work indicates that amylose coated tablet formulations are promising vehicles for drug delivery to the colon. [Copyright &y& Elsevier]

The purpose of this study was to develop an enzyme-based fermentation system for the in vitro assessment of colonic digestion of amylose films and coatings, and to compare its performance with a conventional fermentation model inoculated with human faecal bacteria. Amylose and ethylcellulose were mixed in different ratios and cast as isolated films, as well as spray coated onto drug-(5-aminosalicylic acid) loaded pellets. Four commercial amylase enzymes were individually screened for their ability to digest amylose cast films. The enzyme from the bacterium Bacillus licheniformis was found to be the most active against this substrate. Digestion of mixed amylose and ethylcellulose films was also observed, with the extent of digestion being proportional to the quantity of amylose present in the film. In terms of product performance, drug release from coated pellets was accelerated in the presence of the enzyme. The results with the enzyme system were comparable to those obtained from a faecal-based fermentation model, thereby suggesting that such a system has practical potential for in vitro screening of putative amylose formulations for colonic drug delivery. [Copyright &y& Elsevier]

The oxidative behaviour of 5-aminosalicylic acid (5-ASA) has been investigated by differential pulse voltammetry using a glassy carbon electrode in different buffer systems. Linear sweep voltammetry was used to study the influence of pH on the peak current and peak potential. The solution conditions and instrumental parameters were optimized to obtain a good sensitivity. The Britton–Robinson buffer of pH 1.81 was selected as a suitable analytical medium in which 5-ASA exhibited a sensitive diffusion controlled oxidative peak at 0.564 V (vs. Ag/AgCl). The peak current varied linearly with drug concentration in the range between 1×10−4 and 2×10−6 M. The proposed voltammetric method has been applied to the determination of the drug in commercial delayed-release tablet forms. A mean recovery of 101.23% with a relative standard deviation of 1.35% was obtained. [Copyright &y& Elsevier]

[Display omitted] • Mesalazine is determined by spectrophotometry using a furan ring-opening reaction. • Mesalazine is selectively assayed with a wide linearity range (155-fold). • CCD study showed that absorbance is dependent to the interactions of the parameters. • 1H NMR studies showed that the colored product is being changed to a cyclic isomer. • Density functional theory shows that the colored product is excited locally. A novel and efficient non-azo formation based method was developed for trace sensing of mesalazine (MES), a pharmaceutical aromatic amine. MES was simply coupled with a Meldrum's activated furan (MAF) reagent via a furan ring opening reaction to form a colored product. The intense purple colored solution was detected at 575 nm. The reaction of MES with MAF was monitored by employing 1H NMR spectroscopy and mass spectrometry. In addition, density functional theory (DFT) was applied to optimize the structure of the colored product and its λ max (the wavelength of maximum absorbance) in dimethyl sulfoxide and water. The colored product was considered in three possible structures, and the most possible structures in dimethyl sulfoxide and in water were identified by employing the DFT calculations. Both of the most possible structures indicated only a local excitation in their λ max and no charge transfer was observed. However, one of the structures in dimethyl sulfoxide presented charge transfer properties occurring through N C C C moiety. A univariate optimization method was also used to attain the optimum condition for analysis. In addition, the dependence of the analytical response on the three main affecting parameters (reaction time (X 1), Triton X-100 concentration (X 2) and MAF concentration (X 3)) was identified by employing a central composite design (CCD) approach. The CCD study showed that the analytical response depends complexly on the parameters. Beer's law was obeyed within the range of 0.06–9.30 μg mL−1 of MES (155 fold linearity) at 575 nm, under the optimum condition introduced by the CCD approach. Also, the limit of detection was obtained 0.04 μg mL−1 of MES. The method showed precision (as relative standard deviation) and accuracy (as recovery) within the ranges of 0.6–3.2 % and 96.3–100.8%, respectively. Various organic and inorganic species, amino-pharmaceuticals, and amino acids were tested to evaluate the selectivity of the method. The selectivity of the analytical method was satisfactory. The method was successfully applied for detection of MES in various water matrices and pharmaceutical tablets. [ABSTRACT FROM AUTHOR]

• Solubility of mesalazine in ChCl/PG DES + water mixtures at different temperatures. • Correlation/back-calculation of the solubility data by some cosolvency models. • Calculation of thermodynamic parameters by using the van't Hoff and Gibbs equations. The solubility and solution thermodynamic properties of mesalazine in the binary mixtures of a deep eutectic solvent (DES) and water are determined by a shake-flask method followed by spectrophotometry method in the temperature range of 293.2–313.2 K. The obtained solubility data are correlated using some linear cosolvency models including the van't Hoff equation, the Apelblat, Jouyban-Acree, Jouyban-Acree-van't Hoff models. The accuracy of each used model is investigated by calculation of the mean relative deviations of the back-calculated solubility data. The apparent thermodynamic properties of mesalazine dissolution in the investigated mixtures are also computed based on the van't Hoff and Gibbs equations. [ABSTRACT FROM AUTHOR]

Qing-Chang-Hua-Shi (QCHS) is a Chinese herbal formula, which is composed of 11 herbs. Studies have also shown that QCHS granules can alleviate colitis in animal models by preventing inflammatory responses and suppressing apoptosis through the MEK/ERK signaling pathway. To determine the efficacy and safety of QCHS granules in patients with moderately active UC. We performed a multicenter, randomized, placebo-controlled, double-blind study of patients with moderately active UC who did not respond to 4 weeks of mesalazine therapy at the maximum dose. Patients were randomly assigned to groups and administered QCHS granules (125 g/day, n = 59) or an identical placebo, which was similar to the QCHS granules in color and taste (125 g/day, n = 60), with continued 5-ASA 4 g/d therapy for 12 weeks. The primary outcome was the rate of clinical response and clinical remission at week 12. The secondary outcomes were health-related quality of life, endoscopic response rate, and mucosal healing rate. Any changes in mucus/bloody stool and diarrhea were recorded. Out of the 119 enrolled patients at 10 different centers in China, 102 patients completed the trial. Clinical remission and clinical response were seen in 31.48% and 92.59% of QCHS-treated patients, and 12.50% and 72.92% of placebo-treated patients, respectively. There was a significant difference between the two treatment groups. More patients receiving QCHS granules vs. placebo achieved remission of mucus/bloody stool (70.37% vs. 47.92%, P = 0.0361). Adverse event rates were similar (QCHS granules 38.33%; placebo 25.42%). In conclusion, QCHS granules were superior to the placebo in introducing clinical remission and mucosal healing, as well as in relieving mucus/blood stool in patients with moderately active and 5-ASA-refractory UC. [ABSTRACT FROM AUTHOR]

Mesalazine (MZ) is a significant anti-inflammatory non-steroid drug prescribed for the prevention of inflammatory bowel diseases (IBD). However, it is very essential for sensitive and selective detection of MZ. The transition metal dichalcogenides (TMDs) have gained much interest due to their excellent electro-catalytic activity and highly conducting properties for these applications. The present research proposes the hydrothermally prepared WS 2 /rGO nanocomposite towards the selective detection of MZ. The physicochemical properties reveal the formation of a hexagonal phase of WS 2 hierarchical flowers with stacked thin nanosheets of rGO. The developed WS 2 /rGO modified GC electrode exhibits a noteworthy lower limit of detection about 0.003 μΜ with good sensitivity ranging 20.71 μAμM−1cm2 which were all achieved within the linear range of 0–300 μM L−1. WS 2 /rGO/GC electrode exhibits subsequent negligible current responses (± 0.1μA) towards the anti-interference capability. The fabricated electrode shows remarkable repeatability, reproducibility, and stability towards MZ. Correspondingly, our electrode exhibits tremendous recovery of MZ in real analytical samples like hemoglobin, bovine serum albumin, human urine, and water which reveals the outstanding potential towards real-time practical application of the developed sensor. [Display omitted] • Hierarchical WS 2 nanoflowers/rGO composite synthesized by hydrothermal method. • WS 2 /rGO modified GCE is fabricated for sensing of anti-inflammatory drug mesalazine. • Increasing the electrolyte-accessible active sites enhances the electrocatalytic activity and sensitivity. • WS 2 /rGO/GCE displays a sensing range of 0–300 μM with outstanding LoD of 3 nM. • Excellent selectivity towards 10 co-existing interfering analogous with retrieval of 97.70% from real samples. [ABSTRACT FROM AUTHOR]

• g-C 3 N 4 /CeVO 4 /SPC electrode is used to determine anti-inflammatory mesalazine drug. • The g-C 3 N 4 /CeVO 4 /SPCE has shown a good sensitivity of 18.92 μA μM−1 cm−2. • A wide working range of 0.002−380 μM and LOD of 0.00547 μM is exhibited using DPV. • Real-time analysis is carried in biological and pharmaceutical samples. Rare-earth metal vanadate has gained much interest in recent years due to its excellent catalytic properties and chemical stability in electrochemical sensors. In this study, we have explored the electrochemical activity of graphitic-carbon nitride (g-C 3 N 4) and hierarchical 3D cerium vanadate (CeVO 4) by using screen printed carbon paste electrode (SPCE) for detection of mesalazine (MEZ). Successfully, g-C 3 N 4 and CeVO 4 were synthesized by using a simple hydrothermal process, and then to form a nanocomposite ultrasonication procedure is approached. To confirm the structural and morphological parameters X-ray diffraction (XRD), X-ray photoelectron spectroscopy, Field-emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM) is being utilized. The g-C 3 N 4 /CeVO 4 /SPCE modified electrode has exhibited superior electrocatalytic performance in detecting MEZ with lower R ct value and with the high active surface area when compared with other electrodes. The prepared sensor has shown good sensitivity 18.92 μA μM−1 cm−2 and with a huge working range of 0.002−380 μM, with a promising trace-level limit of detection of about 0.00547 μM by using differential pulse voltammetry (DPV). Henceforth, g-C 3 N 4 /CeVO 4 /SPCE was carried out to subject real-time application in detecting MEZ in various biological, river water, and pharmaceutical samples which resulted in excellent recovery stating the chosen sensor is applicable in real-time analysis. [ABSTRACT FROM AUTHOR]

The solubility profile of mesalazine in the mixtures of carbitol and ethanol within the temperature range of 293.2–313.2 K is measured and the experimental data are fitted to some reported cosolvency models. Moreover, the density of mesalazine saturated solutions in different solvent compositions at various temperatures as another physico-chemical property is also correlated with the Jouyban-Acree model and the results are reported. In order to study the accuracy of the applied models, the mean relative deviations (MRD %) is computed for the back-calculated solubility or density data. Furthermore, the apparent thermodynamic properties of mesalazine dissolution in the investigated mixed solvents are also calculated by using van't Hoff and Gibbs equations. • Solubility study of mesalazine in carbitol + ethanol mixtures at different temperatures. • Correlation/back-calculation of the solubility data by some cosolvency models. • Calculation of thermodynamic parameters by using the van't Hoff and Gibbs equations. [ABSTRACT FROM AUTHOR]