Mesalamine Tablets Research Articles

Film Coating of Phosphorylated Mandua Starch on Matrix Tablets for pH-Sensitive Release of Mesalamine.

Chemically modified mandua starch was successfully synthesized and applied to coat mesalamine-loaded matrix tablets. The coating material was an aqueous dispersion of mandua starch modified by sodium trimetaphosphate and sodium tripolyphosphate. To investigate the colon-targeting release competence, chemically modified mandua starch film-coated mesalamine tablets were produced using the wet granulation method followed by dip coating. The effect of the coating on the colon-targeted release of the resultant delivery system was inspected in healthy human volunteers and rabbits using roentgenography. The results show that drug release was controlled when the coating level was 10% w/w. The release percentage in the upper gastric phase (pH 1.2, simulated gastric fluid) was less than 6% and reached up to 59.51% w/w after 14 h in simulated colonic fluid. In addition to in vivo roentgenographic studies in healthy rabbits, human volunteer studies proved the colon targeting efficiency of the formulation. These results clearly demonstrated that chemically modified mandua starch has high effectiveness as a novel aqueous coating material for controlled release or colon targeting.

Colon-targeted 3D-Printed mesalamine tablets: Core-shell design and in vitro/ex-vivo evaluation

ObjectivesThe present study is intended to develop a shell-core tablet using a hot melt extrusion (HME)-based dual-nozzle fused deposition modeling (FDM) three-dimensional (3D) printing approach. The primary objective was to establish a sustained-release colonic drug delivery system and improve mesalamine's permeability by incorporating Vitamin E TPGS as a permeation enhancer. MethodThe study utilized Kollidon® SR for sustained release, L-100, and HPMC HME L100 for the tablet's protective shell. Six filament formulations were tested, and the mechanical properties of the shell filaments, including the three-point bending, Hooke's law, and stiffness, were assessed. Drug release profiles of the tablets were evaluated using the USP-II dissolution apparatus, and permeability characteristics were gauged using the non-everted intestinal sac method. Solutions containing 5% w/v mesalamine and 2.5% w/v Vitamin E TPGS were employed, with pure mesalamine as a control. ResultsOptimal filament ratios were identified as 50:50 for the core and 30:70 for Eudragit L-100 to HPMC HME L100 for the shell. The resulting tablets achieved a prolonged drug release of up to 24 h for the core. They ensured minimal drug release in the upper gastrointestinal tract (∼5% in the first 5 h), effectively targeting the colon. Incorporating Vitamin E TPGS led to a 3.6-fold increase in mesalamine absorption compared to the control, and the addition of Kollidon® SR notably improved the flow properties of Mesalamine powder. ConclusionIn conclusion, this innovative approach has the potential to achieve a colon-specific drug delivery system.

Fabrication of iron tin oxide/tin oxide intertwined graphitic carbon nitride hybrid composite electrocatalyst for electrochemical detection of 5-aminosalicylic acid in human urine and pharmaceutical tablet samples

Background5-Aminosalicylic acid (5-ASA) is known as a cornerstone in the treatment of inflammatory bowel diseases, to prevent the synthesis of cytokines and inflammatory mediators. However, an overdose of this drug is a rare and unique condition in patients and can lead to kidney failure. Therefore, a rapidly sensitive method is needed for the monitoring of 5-ASA. Methodswe synthesized novel iron tin oxide/tin oxide (FeSnO3/SnO2, FSO/SO) nanostructures via a facile precipitation method. Further, the FSO/SO intertwined two-dimensional (2D) graphitic carbon nitride (g-C3N4) hybrid composite electrocatalyst was developed by the wet-chemical process. The proposed materials were characterized by XRD, Raman, XPS, FESEM, TEM and TGA. Further, the glassy carbon electrode (GCE) modified with FSO/SO/g-C3N4 was revealed to sensitive detection of 5-ASA in PBS (pH-7) by CV, LSV and DPV methods. Significant findingsThe surface modification of FSO/SO/g-C3N4/GCE can enhance the synergistic action of different dimensional active catalysts. The limit of detection (LOD=3σ/S) proposed sensor was found to be 0.00625 µM and 0.0075 µM via LSV and DPV methods, also the calculated sensitivity has 3.428 µA µM−1 cm−2 and 2.857 µA µM−1 cm−2 respectively. The developed sensor demonstrated outstanding feasibility test results for detecting 5-ASA in samples of human urine and mesalamine tablet using the DPV method.

Calprotectin in Low anterior resection syndrome patients; a new insight into diagnosis and management: A pilot study

Background and study aimLow anterior resection syndrome (LARS) has been reported to occur in up to 80% of patients after low anterior resection (LAR). This study aimed to investigate the role of fecal calprotectin in the diagnosis of LARS in patients subjected to LAR. Patients and methodsThis was a pilot study conducted on a group of patients that developed LARS after LAR who presented to the colorectal unit of Cairo University Hospital from November 2019 to April 2021. Fecal calprotectin levels were measured for all 36 eligible patients with persistent symptoms of LARS and those with high levels were treated using mesalamine tablets (500 mg, with a total of 3 g per day in divided doses) for one month, then 2 g per day for the subsequent five months. ResultsThe study participants were treated using mesalamine and re-evaluated after six months. Twenty (55.5%) of the 36 patients experienced marked improvement while 10 (27.7%) improved from major to minor LARS with decreased levels of calprotectin. Six (16.6%) patients showed no significant improvement in symptoms (high LARS score) and still had high levels of fecal calprotectin. ConclusionFecal calprotectin can be a useful tool in the diagnosis and treatment planning of persistent LARS. Our study also demonstrated the efficacy of immune modulators such as mesalamine (pentasa) in treating LARS in patients who are unresponsive to conventional dietary restrictions.

Trace level electrochemical detection of mesalazine in human urine sample using poly (N-Vinyl)-2-Pyrrolidone capped Bi-EDTA complex sheets incorporated with ultrasonically exfoliated graphene oxide

Trace level detection of drugs and hazardous analytes is more critical in electrochemical sensor. In this work, a simple sonochemical-assisted synthesis of Bismuth-EDTA complex/GO flakes was achieved and was developed to analyze mesalazine (MSA) sensing. The 3D hollow bricks were obtained for the Bi-EDTA complex without PVP. Surprisingly, PVP influenced the formation of broken glass-like structured for PVP with Bi-EDTA complex. Bi-EDTA complex modified GCE was developed to determine the role of PVP and its activity in electrochemical sensors. The results obtained by modifying the electrode Bi-EDTA complex with PVP showed good electrochemical performance compared to bare and other controls like GO and Bi-EDTA complex without PVP. The synergetic effect and high electroactive sites of Bi-EDTA complex/GO modified sensor implied low LOD (0.55 nM) and wide linear range from 0.005–585 µM. Furthermore, Bi-EDTA complex/GO showed an excellent selectivity in sensing MSA. Moreover, the Bi-EDTA complex exhibits advantages such as good stability, reproducibility, and repeatability. The modified Bi-EDTA complex/GCE sensor has been practically done to determine trace levels of MSA in human urine samples containing mesalamine tablets with satisfactory results.

Formulation and Evaluation of Sustained Release Colon Targeted Mesalamine Tablet

Formulation and Evaluation of Sustained Release Colon Targeted Mesalamine Tablet

Bioavailability and swallowability of an age-appropriate, delayed-release mesalamine formulation in healthy volunteers.

Objective: Delayed-release mesalamine 400 mg capsules containing four 100 mg tablets have been developed for children with ulcerative colitis who have difficulty swallowing. Bioavailability of the mesalamine capsules was compared with existing mesalamine tablets in healthy adults, and the effect of food on bioavailability from mesalamine capsules was determined. Tablet swallowability in healthy children was evaluated.Methods: In the open-label, replicate-treatment, single-dose, crossover, comparative bioavailability study, healthy adult volunteers were randomized to one of four treatment sequences to receive mesalamine 400 mg tablets (fasted) twice, mesalamine 400 mg capsules (fasted) twice, and a mesalamine 400 mg capsule (with food) once, with ≥7 days between treatments. Pharmacokinetic (PK) parameters were calculated and analyzed using the reference-scaled average bioequivalence procedure. In the open-label, single-dose swallowability study, healthy children aged 5–11 years were asked to swallow eight placebo tablets identical to those contained in two mesalamine capsules.Results: In the bioavailability study (n=160), mesalamine capsules and tablets in fasted volunteers exhibited similarly delayed absorption and were shown to be bioequivalent; statistical parameters calculated from PK values met the criteria for bioequivalence. A slight increase in mesalamine bioavailability was observed with food administration, but the delayed-release performance of the capsules was not affected. Overall safety profiles between capsules and tablets were similar. In the swallowability study (n=60), the majority of children swallowed eight placebo tablets, with slight variability between age groups.Conclusion: Evaluation of PK parameters confirmed mesalamine capsules are bioequivalent to mesalamine tablets. Mesalamine capsules were well tolerated, can be administered with or without food, and are an age-appropriate product for children.

Changes in health-related quality of life and work-related outcomes for patients with mild-to-moderate ulcerative colitis receiving short-term and long-term treatment with multimatrix mesalamine: a prospective, open-label study

BackgroundUlcerative colitis (UC) is associated with lower health-related quality of life (HRQoL), and with disease activity predicting lower HRQoL and worse work-related outcomes. The current study examined the burden of UC on patients’ HRQoL, as well as changes in patients’ HRQoL and work-related outcomes following short-term and long-term treatment with multimatrix mesalamine, and their correspondence with changes in disease activity.MethodsData were from an open-label, multinational, prospective trial (ClinicalTrials.gov identifier: NCT01124149) of 717 adults with active mild-to-moderate UC who were treated with 4.8 g/day multimatrix mesalamine tablets once daily for eight weeks (acute phase). Four-hundred sixty-one patients who achieved partial or complete clinical and endoscopic remission subsequently received treatment with daily 2.4 g/day multimatrix mesalamine for 12 months (maintenance phase). At baseline, Week 8, and Month 12, patients were administered patient-reported outcomes (PRO) measures of HRQoL (the SF-12v2® Health Survey [SF-12v2] and Short Inflammatory Bowel Disease Questionnaire) and work-related outcomes (Work Productivity and Activity Impairment questionnaire, UC-specific version). SF-12v2 scores were compared to the U.S. general population using Analysis of Variance models to assess burden of UC on HRQoL. Mixed-effects repeated-measures models compared PRO scores across visits to assess change in PRO scores over time. Correlations examined the correspondence of changes in PRO scores with changes on a modified UC disease activity index (UC-DAI).ResultsBaseline burden of disease observed on all SF-12v2 domains was partially eliminated at Week 8 and completely eliminated at Month 12. Statistically significant improvements from baseline were observed at both Week 8 and Month 12 for all PRO scores (all P < 0.001). Decreases in UC-DAI scores significantly predicted improvements in PRO scores during the acute treatment phase.ConclusionsPatients with UC receiving daily multimatrix mesalamine treatment showed significant improvements in all measured domains of HRQoL and work-related outcomes. Patients who achieved partial or complete clinical and endoscopic remission maintained these improvements for most of these domains over 12 months with continued daily treatment. Changes in HRQoL and work-related outcomes were inversely related to changes in disease activity. Findings support the effectiveness of multimatrix mesalamine for improving, and sustaining improvements, in HRQoL and work-related outcomes.

Design, development and in vitro evaluation of sequentially optimized mesalamine tablets for optimum colonic delivery

Design, development and in vitro evaluation of sequentially optimized mesalamine tablets for optimum colonic delivery

Studies on the Development and Evaluation of Colon Targeted Mesalamine Tablets based on Eudragit L100-Chitosan Interpolyelectrolye Complexes

An attempt was made to prepare and evaluate colon targeted Mesalamine tablets based on interpolyelectrolyte complex. Tablets were prepared by wet granulation technique using varying ratios of Eudragit L100 (EL) and Chitosan (CS) polymers. Results obtained showed that the tablets conformed to compendial requirements for acceptance and CS and EL formed IPECs that showed pH-dependent swelling properties and prolonged the in vitro release of Mesalamine from the tablets in the following descending order: 3 : 2 > 2 : 3 > 1 : 1 ratios of CS and EL. An electrostatic interaction between the carbonyl (-CO-) group of EL and amino (-NH3 +) group of CS of the tablets formulated with the IPECs was capable of preventing drug release in the stomach and small intestine and helped in delivering the drug to the colon. Kinetic analysis of drug release profiles showed that the systems predominantly released Mesalamine in a zero-order manner.

Tu1197 MicroRNA-4284 Regulates CXCL5 Expression and Is Down-Regulated in Colon Tissues of Pediatric Patients With Ulcerative Colitis

AIM: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon and rectum distinguished by relapsing and remitting gastrointestinal and systemic symptoms. Mesalamine (5-aminosalicylic acid; 5-ASA) has proven efficacy in the induction and maintenance of disease remission in patients with mild-to-moderate UC. This phase 1, multicenter, randomized, open-label study (NCT01130844) assessed the pharmacokinetic and safety profiles of 5-ASA and its major metabolite, acetyl-5-ASA (Ac-5-ASA), after administration of once-daily MMX mesalamine to children and adolescents with UC. METHODS: Study participants aged 5-17 years, with a UC diagnosis of ≥3 months were randomized to MMX mesalamine 30, 60, or 100 mg/kg/day (stratified by body weight) for 7 days. To achieve these doses in children, smaller-sized 300 mg and 600 mg tablets were developed for this study to augment the existing approved 1200 mg MMX mesalamine tablet. Patients were administered MMX mesalamine at home on Days 1-4 and on site on Days 5-7 when subjects attended for pharmacokinetic blood and urine sampling and for safety assessments. Plasma and urine concentrations of 5-ASA and Ac-5-ASA were determined by a validated LC/MS/MS assay. Key pharmacokinetic parameters for 5-ASA and Ac-5-ASA included maximum concentration (Cmax,ss), time of Cmax,ss (tmax), area under the curve for one dose interval (AUCss), and renal clearance (CLR), and percent of dose absorbed. RESULTS: A total of 52 patients (30F:22M with mean [standard deviation] age of 13.3 [3.06] years and median [range] time since UC diagnosis of 1.83 [0.2, 9.6] years) were randomized and treated: 21 at 30 mg/kg; 22 at 60 mg/kg; and 9 at 100 mg/kg. Steady state plasma concentrations for 5-ASA and Ac5-ASA were attained by Day 5 for all doses. On Day 7, mean AUCss and Cmax,ss for 5-ASA and Ac-5-ASA increased in a dose proportional manner between 30 and 60 mg/kg/day doses. Mean percentage of 5-ASA absorbed from MMX mesalamine was 29.4%, 27.0%, and 22.1%, for 30, 60, and 100 mg/kg/day doses, respectively. Mean CLR ranged from 5.0-6.5 L/h for 5-ASA and 10.0-16.2 L/h for Ac-5-ASA. The incidence of treatment-emergent adverse events was 19.2% overall. Events were similar among different dose and age groups, with no novel safety signals reported. CONCLUSIONS: The pharmacokinetic profile of 5-ASA and Ac-5ASA in children/adolescents with UC receiving MMX mesalamine across all dose levels was similar to the pharmacokinetic profile in historical adult data. MMX mesalamine was welltolerated at all doses and in all age groups; no new safety signals were identified.

Tu1196 Evaluation of the Pharmacokinetics and Safety of MMX Mesalamine Following Administration in Children and Adolescents With Ulcerative Colitis

AIM: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon and rectum distinguished by relapsing and remitting gastrointestinal and systemic symptoms. Mesalamine (5-aminosalicylic acid; 5-ASA) has proven efficacy in the induction and maintenance of disease remission in patients with mild-to-moderate UC. This phase 1, multicenter, randomized, open-label study (NCT01130844) assessed the pharmacokinetic and safety profiles of 5-ASA and its major metabolite, acetyl-5-ASA (Ac-5-ASA), after administration of once-daily MMX mesalamine to children and adolescents with UC. METHODS: Study participants aged 5-17 years, with a UC diagnosis of ≥3 months were randomized to MMX mesalamine 30, 60, or 100 mg/kg/day (stratified by body weight) for 7 days. To achieve these doses in children, smaller-sized 300 mg and 600 mg tablets were developed for this study to augment the existing approved 1200 mg MMX mesalamine tablet. Patients were administered MMX mesalamine at home on Days 1-4 and on site on Days 5-7 when subjects attended for pharmacokinetic blood and urine sampling and for safety assessments. Plasma and urine concentrations of 5-ASA and Ac-5-ASA were determined by a validated LC/MS/MS assay. Key pharmacokinetic parameters for 5-ASA and Ac-5-ASA included maximum concentration (Cmax,ss), time of Cmax,ss (tmax), area under the curve for one dose interval (AUCss), and renal clearance (CLR), and percent of dose absorbed. RESULTS: A total of 52 patients (30F:22M with mean [standard deviation] age of 13.3 [3.06] years and median [range] time since UC diagnosis of 1.83 [0.2, 9.6] years) were randomized and treated: 21 at 30 mg/kg; 22 at 60 mg/kg; and 9 at 100 mg/kg. Steady state plasma concentrations for 5-ASA and Ac5-ASA were attained by Day 5 for all doses. On Day 7, mean AUCss and Cmax,ss for 5-ASA and Ac-5-ASA increased in a dose proportional manner between 30 and 60 mg/kg/day doses. Mean percentage of 5-ASA absorbed from MMX mesalamine was 29.4%, 27.0%, and 22.1%, for 30, 60, and 100 mg/kg/day doses, respectively. Mean CLR ranged from 5.0-6.5 L/h for 5-ASA and 10.0-16.2 L/h for Ac-5-ASA. The incidence of treatment-emergent adverse events was 19.2% overall. Events were similar among different dose and age groups, with no novel safety signals reported. CONCLUSIONS: The pharmacokinetic profile of 5-ASA and Ac-5ASA in children/adolescents with UC receiving MMX mesalamine across all dose levels was similar to the pharmacokinetic profile in historical adult data. MMX mesalamine was welltolerated at all doses and in all age groups; no new safety signals were identified.

Exploiting the synergistic effect of chitosan–EDTA conjugate with MSA for the early recovery from colitis

The present study was aimed to exploit the antibacterial/antifungal and film coating potential of Chitosan–EDTA (CH–EDTA) conjugate in combination with mesalamine (anti-inflammatory agent) for the early recovery from TNBS induced coilitis. The results suggested CH:EDTA (1:1) spray coated mesalamine tablets has an ability to transport drug in buffer pH 6.8 with rat caecal content condition. The CH–EDTA shows high level of adhesiveness of coat with core tablet. Further, FTIR, DSC and SEM analysis suggested spray coating of CH–EDTA on tablets was beneficial as compared to ladling method as it enhances interaction density and showed resistance from pH (1.2, 6.8 and 7.4). The pharmacokinetic parameters, AUC and AUMC of spray coated tablets were respectively, 4.70 fold and 2.10 fold increased. A synergistic therapeutic effect with CH–EDTA spray coated mesalamine was observed as evaluated by colon/body weight ratio, clinical activity score and damage score. X ray image study supported that CH–EDTA conjugate successfully delivered MSA tablets to large intestine. Histopathology of colon tissues showed rapid recovery from TNBS induced colitis in rats within 4 days. The findings revealed decreased recovery period was due to combined effect of both CH–EDTA and MSA to treat TNBS induced colitis.

Formulation development, optimization and study on drug release kinetics of Eudragit® L100-HPMC E15 LV mixed film-coated colon- targeted Mesalamine tablets

The study was designed to evaluate the in vitro dissolution characteristics of pH-sensitive polymer - HPMC E 15 LV-coated tablets - in various simulated fluids (pH range 1.2, 6, 7.2). The Mesalamine tablets were fabricated by mixing the drug with microcrystalline cellulose and other ingredients.The fabricated Mesalamine tablets were coated with Eudragit L100 polymer and HPMC E 15 LV. The fluctuation in colonic pH conditions during inflammatory bowel disease and the nature of less fluid content in the colon may limit the expected drug release in the colon. Addition of HPMC E 15 LV may control this problem by hydrophilic nature and excellent film-forming characteristics like ductility and elasticity. The different batches of Mesalamine tablets (FM1-FM5) were coated with increasing concentration of Eudragit L100 and HPMC E 15 LV. The coating was given up to 8% TWG(Total weight gain) of the uncoated tablet. Drug release studies were conducted in different pH conditions in the presence of rat ceaecal contents. The different buffer conditions were chosen to mimic the pH changes in the terminal part of the ileum as well as in the colon. The drug release profile was analyzed for colon-targeting performance in vitro. The release profile of the tablets indicates that the drug release was retarded in the tablet by film coating. The addition of HPMC E 15 LV ensures the channels for allowing colonic fluids to penetrate into the core and subsequent drug release at the target site. The kinetics of the drug release also evaluated the release pattern that was best fitted with Higuchian release. The results of the mechanism of release revealed that drug release was found to be a complex one with diffusion, erosion and swelling.

Formulation development, optimization and study on drug release kinetics of Eudragit®L100-HPMC E15 LV mixed film-coated colon-targeted Mesalamine tablets

Formulation development, optimization and study on drug release kinetics of Eudragit^®L100-HPMC E15 LV mixed film-coated colon-targeted Mesalamine tablets

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

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. 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. 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. 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.

A Randomized, Open-Label, Parallel-Group Study to Determine the Pharmacokinetics (PK), Safety and Tolerability of Delayed-Release Mesalamine Tablets in Children and Adolescents with Active Ulcerative Colitis (UC)

A Randomized, Open-Label, Parallel-Group Study to Determine the Pharmacokinetics (PK), Safety and Tolerability of Delayed-Release Mesalamine Tablets in Children and Adolescents with Active Ulcerative Colitis (UC)

5-Aminosalicylic Acid and its major metabolite levels in patients with moderately active ulcerative Colitis following oral administration of delayed-release Mesa lamine tablets

5-Aminosalicylic Acid and its major metabolite levels in patients with moderately active ulcerative Colitis following oral administration of delayed-release Mesa lamine tablets

5-Aminosalicylic Acid and its major metabolite levels in patients with moderately active ulcerative Colitis following oral administration of delayed-release Mesalamine tablets

To evaluate the systemic exposure to 5-aminosalicylic acid (5-ASA) and its major metabolite, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) in patients with moderately active ulcerative colitis (UC). Sparse samples for pharmacokinetic analysis were obtained in patients with moderately active UC enrolled in two randomized, double-blind, 6-week, activecontrol clinical studies (ASCEND I & II) that compared mesalamine 4.8 g/day (800 mg tablet) to mesalamine 2.4 g/day (delayed-relese mesalamine 400 mg tablet). The dosing regimen for both treatment groups was 2 tablets administered 3 times daily. Bioanalysis of the concentrations of 5-ASA and N-Ac-5-ASA in plasma samples obtained at baseline and after 3 and 6 weeks of drug administration was performed in a blinded manner using a validated, sensitive, and specific high-performance liquid chromatography (HPLC) assay with mass spectrometric (MS) detection. Plasma concentrations of 5-ASA and N-Ac-5-ASA were summarized using descriptive statistics. Safety assessments included adverse events (AEs), physical examinations, vital signs, and clinical laboratory evaluations. A total of 448 patients with moderate UC were randomized in the 2 studies. There was a dose-related increase in systemic exposure at Weeks 3 and 6 for both 5-ASA and N-Ac-5-ASA in patients with moderately active UC with no added safety implications. Mean Plasma Concentrations (ng/mL) of 5-ASA and N-Ac-5-ASA Mean Plasma Concentrations (ng/mL) of 5-ASA and N-Ac-5-ASA The expected dose-related increase in systemic exposure was observed in this moderately active UC patient population. Importantly, although exposure increased, the clinical safety profiles were comparable across the two dose levels.

5-Aminosalicylic Acid Release from pH-Dependent, Delayed-Release Formulations

Purpose: Many delayed-release formulations of 5 aminosalicylic acid (5-ASA) utilise pH-dependent coatings to resist gastric breakdown, and release active drug at intestinal pH values. However, in patients with ulcerative colitis, the pH of ileo-caecal region of the gastrointestinal tract can vary between 6.8–7.2. Here, we analyse coating thickness and release characteristics of MMX™ mesalamine 1.2 g tablets (Lialda®[USA], Shire Pharmaceuticals Inc., Wayne, PA, USA) in different pH conditions and put the results into context using published literature for another pH-dependent delayed-release mesalamine formulation. Methods: Three batches of MMX mesalamine tablets were analyzed using non-destructive three-dimensional terahertz pulse imaging to determine film coat thickness and morphology. Dissolution testing using USP II apparatus (50 rpm) was subsequently performed at pH 6.8 and 7.2. Findings were put into context using previous data for pH-dependent, delayed-release mesalamine tablets (400 mg) that were obtained using a similar methodology (Spencer et al, J Pharm Sci, 2007). Results: The mean (±standard deviation) coating thicknesses of MMX mesalamine tablets from each of the three batches were 109.2 (±16.8), 113.1 (±19.5) and 113.8 μm (±19.8), with a maximum variance of 17.2% of the total coating thickness. MMX mesalamine tablets demonstrated steady release of 5-ASA at both pH values, with complete release achieved over > 8 hours at pH 6.8 and over > 12 hours at pH 7.2. Spencer et al (2007) reported coating thicknesses of 76.8 (±18.2), 78.0 (±14.0) and 80.5μm (±12.5), with a maximum variance in total coating thickness of 23.7% for three test batches. 5-ASA release from these batches was consistent over the initial 2 hours at pH 7.2, but at pH 6.8 5-ASA release was variable. Complete release of 5-ASA was variable, with 80–100% tablet disintegration occurring within 2 hours. Conclusion: The release profile of 5-ASA from pH-dependent formulations is of utmost importance since it determines the concentration of active drug delivered to the site (s) of inflammation. MMX mesalamine tablets appear to have consistent coating thickness which, with MMX drug-release technology, may contribute to the consistent and steady release of 5-ASA at both pH 6.8 and 7.2 reported here. These characteristics do not appear to be common to all pH-dependent formulations, as evidenced by previously published data.