Controlled-release Mesalazine Research Articles

P534 The preference for controlled-release mesalazine formulation of 2 g-granule sachet in patients already experienced 1 g-tablet

Abstract Background The important factor is a good adherence in the treatment of inflammatory bowel disease (IBD) and the major guidelines recommend that the choice of formulation of mesalazine should consider patient preference and likely adherence. This study was to evaluate the preference for controlled-release (CR) mesalazine 2 g-granule sachet in patients who have been already experienced CR mesalazine 1 g-tablet and its related clinical factors. Methods First was treatment with 4 g CR mesalazine a day as two 2 g-granule sachets for 2 weeks in patients with IBD in remission who have already taken 4 g CR mesalazine a day as four 1 g-tablets for more than 3 months in Kosin University Gospel Hospital, Korea. The patients were consecutively enrolled. Second were the patients’ survey with 10 questionnaires about preferences (Table 1) after the 2 week-treatment and medical review of clinical information of patients. Results A total of 80 patients (46 in ulcerative colitis and 34 in Crohn’s disease, and 54 of male) were enrolled. Previous use of CR mesalazine four 1 g-tablets a day more than 1 year was in 88.6% of patients. In preference of formulation by ease to swallow, 70.0% of patients answered 2 g-granule sachet was better but just 20.0% of patients answered 1 g-tablet was better. In preference of formulation by next prescription, that is about overall preference, 63.8% of patients answered granule was better but 30.0% for tablet. In the number of 1 g-tablet or 2 g-granule sachet able to be swallowed at once, 46.9% of patients could swallow one or less tablet (1 g or less) and 96.1% of patients could swallow one or two sachets (2 g or more) (Fig. 1). When the patients who chose ‘granule was much better or better in overall preference' are classified as granule preference group and the remaining as others group. Number of tablet able to be swallowed at once in the medication before the granule trial was significantly less in granule preference group compared to others group (1.6 tablet vs. 2.0 tablet) (Fig. 2). However, the other factors including age, sex, body weight, height, body mass index, type of disease, concomitant oral medications, previous duration of 1 g-tablet use, were not associated with the overall preference. Conclusion In patients already experienced CR mesalazine 1 g-tablet for a long time, two-thirds of the patients more preferred to be prescribed 2 g-granule sachet and the preference was associated with the ability to swallow 1 g-tablets at once. Not only CR mesalazine 1 g-tablet but also 2 g-granule sachet can be an excellent choice for improving adherence of mesalazine treatment in IBD, especially when it comes to patients who can't take two or more 1 g-tablets at once.

Corrigendum: Randomized, crossover questionnaire survey of acceptabilities of controlled-release mesalazine tablets and granules in ulcerative colitis patients.

Corrigendum: Randomized, crossover questionnaire survey of acceptabilities of controlled-release mesalazine tablets and granules in ulcerative colitis patients.

Randomized, crossover questionnaire survey of acceptabilities of controlled-release mesalazine tablets and granules in ulcerative colitis patients.

Background/AimsOral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey.MethodsUC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed.ResultsA total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139).ConclusionsCR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication.

Comparison of efficacy of once daily multimatrix mesalazine 2.4 g/day and 4.8 g/day with other 5-aminosalicylic acid preparation in active ulcerative colitis: a randomized, double-blind study.

Background/AimsThis study compared the efficacy of multimatrix mesalazine 2.4 g/day and 4.8 g/day with controlled-release mesalazine 2.25 g/day.MethodsIn this multicenter, randomized, double-blind study, 251 patients with mildly to moderately active ulcerative colitis received multimatrix mesalazine 2.4 g/day once daily (Multimatrix-2.4), 4.8 g/day once daily (Multimatrix-4.8), or controlled-release (time-dependent) mesalazine 2.25 g/day 3 times daily (Time-2.25) for 8 weeks. The primary efficacy endpoint was the change in the ulcerative colitis-disease activity index (UC-DAI) score.ResultsThe mean change in the UC-DAI score and standard deviation in the per protocol set was −1.9±2.5 for Multimatrix-2.4 and −2.4±2.8 for Time-2.25. The difference between Multimatrix-2.4 and Time-2.25 was 0.3 (two-sided 95% confidence interval [CI], −0.5 to 1.1), thus non-inferiority was not demonstrated based on the pre-defined non-inferiority margin (1.0). In the full analysis set, the difference between Multimatrix-4.8 and Time-2.25 was −1.2 (two-sided 95% CI, −2.0 to −0.5), and the mean change in UC-DAI score in the FAS was −3.3 (two-sided 95% CI, −3.9 to −2.8) for Multimatrix-4.8 and −1.9 (two-sided 95% CI, −2.5 to −1.3) for Multimatrix-2.4, indicating that Multimatrix-4.8 was more effective than Time-2.25 and Multimatrix-2.4. There was no difference among the treatment groups in terms of safety.ConclusionsThis study showed that the efficacy of multimatrix mesalazine 2.4 g/day was comparable to controlled release mesalazine 2.25 g/day, although non-inferiority was not demonstrated. Importantly, this was the first study to indicate that multimatrix mesalazine 4.8 g/day was more effective than 2.4g/day with no associated safety concerns.

Comparison of efficacies of once-daily dose multimatrix mesalazine and multiple-dose mesalazine for the maintenance of remission in ulcerative colitis: a randomized, double-blind study.

Background/AimsThis study compared the efficacy of once-daily administration of multimatrix mesalazine 2.4 g/day with multiple-dose mesalazine for the maintenance of remission.MethodsIn this multicenter, randomized, double-blind study, 203 patients with ulcerative colitis in remission received multimatrix mesalazine 2.4 g/day once-daily or time-dependent (controlled-release) mesalazine 2.25 g/day 3 times-daily for 48 weeks. The primary efficacy endpoint was the proportion of patients without rectal bleeding.ResultsThe proportion of patients without rectal bleeding during the 48-week treatment period in the per protocol set was 84.8% (84/99) in the multimatrix mesalazine 2.4 g/day group and 78.0% (78/100) in the controlled-release mesalazine 2.25 g/day group. The difference between the 2 treatment groups was 6.8% (two-sided 95% confidence interval, −3.9% to 17.6%). The noninferiority margin of −10% was met in the comparison of multimatrix mesalazine 2.4 g/day once-daily with controlled-release mesalazine 2.25 g/day. Multimatrix mesalazine 2.4 g/day once-daily demonstrated consistent efficacy in all subgroups. There was no difference between the 2 treatment groups with regard to safety.ConclusionsA once-daily dose of 2 multimatrix mesalazine tablets (2.4 g) was not inferior to controlled-release mesalazine 2.25 g/day 3 times-daily in maintaining absence of rectal bleeding in ulcerative colitis.

Efficacy of a pH-dependent controlled-release mesalazine based on clinical and endoscopic assessment for ulcerative colitis: a retrospective cohort study.

BackgroundWe conducted a retrospective cohort study to clinically and endoscopically assess the efficacy of delayed-release mesalazine for ulcerative colitis.MethodsThe study included 104 ulcerative colitis patients (52 men, 52 women) initiated on treatment with delayed-release mesalazine between 2009 and 2012. The clinical symptoms at months 0, 1, and 12 were scored using the clinical activity index. An endoscopic index was also used to determine disease activity in 72 patients who underwent total colonoscopy before and after mesalazine treatment.ResultsThe clinical activity index at months 0, 1, and 12 were 4.6±2.8, 3.4±1.8, and 2.8±1.4, respectively, decreasing with time after the start of mesalazine treatment (P<0.001). The endoscopic index decreased significantly from 4.5±3.2 before to 3.1±2.8 after the start of delayed-release mesalazine treatment in the mean follow-up period of 1.0±0.4 years (P<0.001).ConclusionDelayed-release mesalazine was confirmed to be effective both clinically and endoscopically.

Systematic review: the potential influence of mesalazine formulation on maintenance of remission in Crohn’s disease

To evaluate the effectiveness of pH 6-/pH 7-dependent and controlled-release mesalazines in maintaining medically and surgically induced Crohn's disease remission. A systematic search identified 13 randomized controlled trials (RCTs). The rate of symptomatic relapse (Crohn's disease activity index >150, or an increase in baseline by at least 60-100 points) was extracted from each randomized controlled trial. Pooled odds ratios (OR), the number needed to treat (NNT), and percentage therapeutic benefit (absolute risk reduction) were calculated. Treatment with pH 7-dependent mesalazine significantly reduced the risk of relapse in patients with either surgically [OR 0.28; 95% confidence interval (CI) 0.12-0.65; P = 0.0032] or medically induced remission (OR 0.38; 95% CI 0.17-0.85; P = 0.0113). However, treatment with controlled-release mesalazine and pH 6-dependent mesalazine failed to show any significant advantage over placebo. The NNT to maintain surgically or medically induced remission was lowest for pH 7-dependent mesalazine (NNT = 4 and 5, respectively; NNT = 15 and 16 for controlled-release mesalazine and NNT = 11 and 23 for pH 6-dependent mesalazine). Therapeutic benefit was highest for pH 7-dependent mesalazine (surgical = 30.6%, medical = 22.8%). This compared with 6.9% (surgical) and 6.4% (medical) for controlled-release mesalazine, and 9.8% and 4.4%, respectively, for pH 6-dependent mesalazine. Further trials of pH 7-dependent mesalazine formulations are warranted in the maintenance of remission in Crohn's disease.

訂正

訂正

調剤時に一回量包装されたメサラジン錠の着色とその安定性

Recently, automatic tablet counting and packaging machines have come to be widely used for the one-dose packaging of tablets and capsules. However, coloration, i.e. changes in color, of such tablets repackaged by one-dose packaging machins for dispensing has been frequently observed in several kinds of tablets due to the light, humidity and temperature in the room. In this report, the changes observed over time in the controlled-release mesalazine product, Pentasa® tablets, repackaged with polyethylene-laminated cellophane and glassine films for the one-dose packaging was studied.The repackaged tablets changed color within a week at room conditions (22-25°C, 50-70% RH) under a 350 lux fluorescent white-1 amp ex posure for 12 h per day or in darkness. However, no coloration was observed for at least four weeks in a refrigerator (4°C, 20% RH) in dark ness. The weight of the repackaged tablets increased by about 1% at room conditions within a week, while no such weight increase in the tablets was observed while the tablets were kept in a refrigerator. No changes in the amounts of mesalazine and its degradates, gentigic acid and p-aminophenol, in the tablets were observed and the dissolution properties of mesalazine from the tablets also remained unchanged during the experimental period.Based on these findings, we conclude that the one-dose packaging of Pentasa® tablets is not a suitable procedure since it results in the absorption of moisture and changes in color.

Dissolution profiles of mesalazine formulationsin vitro

In vitro dissolution profiles of three controlled-release mesalazine formulations were determined at pH 1.0, 6.0 and 7.5. A closed-column type dissolution apparatus was used. A reproducible gradual dissolution profile was seen for Pentasa at all pH values. Dissolution starts immediately and is complete after 20 h. Dissolution profiles at pH 1 and pH 7.5 are much alike and dissolution is faster than at pH 6. The behaviour of Asacol at different pH values corresponds with the expectations: no release at pH 6 and pH 1, fast release at pH 7.5. Dissolution starts after 1 h and is complete after 3 h. Mesalazine release from Salofalk tablets at pH 7.5 and pH 6.0 starts after 2 and 3 h, respectively, and is complete after 5 and 10 h. However, after a long lag-time (10 h) mesalazine is also released from Salofalk tablets at pH 1 and dissolution is complete after 23 h.