Endoscopic balloon dilatation of Crohnʼs Disease strictures

Introduction: Stricturing is a common complication of Crohn's disease. Endoscopic balloon dilatation (EBD) offers a valuable alternative to surgical intervention, but there are limited data on factors influencing its safety and efficacy. Methods: A multicenter retrospective audit across 4 U.K. teaching hospitals was performed on the use of EBD for Crohn's strictures between 1998 and 2011. Demographics, smoking status, medications, C-reactive protein, endoscopic findings, and subsequent surgery at follow-up were recorded. Success of EBD was defined as symptomatic improvement without the need for surgery at follow-up. Results: Seventy-nine patients (47 women; median age, 48 yr) were identified for this study. Forty-eight (61%) patients had ileocolonic anastomotic strictures, whereas the rest had de novo strictures. In total, 191 EBDs (range, 1-11; median 2) were carried out on 93 strictures (range, 1-5; median 1) over a median duration of 12 months (range, 1-84). There were no serious adverse events. Success at index EBD was 34%, with a further 43% achieving long-term benefit from additional EBDs. Eighteen (23%) patients required surgery. Time to surgery after the first EDB was 2.6 to 71.1 months (median, 12.8 mo). Longer Crohn's disease duration (P = 0.03) and high C-reactive protein (P = 0.008) were associated with an increased need for subsequent surgery. Conclusions: EBD was safe and effective in achieving long-term symptom improvement and avoidance of surgery in most patients. Prospective controlled trials are needed to evaluate the effect of other factors, including Crohn's disease phenotype, and the role of concomitant medication to identify those best suited to EBD

Method Development, Validation and Stability Indicating Studies for Simultaneous Estimation of Anti-Hypertensive Drugs from Pharmaceutical Formulation by RP-HPLC

Objective: Method development, validation & stability indicating studies for simultaneous estimation of Anti-Hypertensive drugs, Benidepine (BEN) and Metoprolol (MET) from pharmaceutical formulation by RP-HPLC. Methods: For present work, reverse phase chromatography was selected as its suggested use for ionic and moderate to non-polar compounds. Reverse phase chromatography is simple, suitable, better regarding efficiency, stability, and reproducibility. C18 packed column, a 100 X 2.1mm. ID column of 5.0 μm particle packing, was selected for separation of BEN and MET. Different solvent systems were tried and optimized in combinations as mobile phase. BEN (4 μg/ml) and MET (50 μg/ml) in 15mM ammonium formate-Methanol (15:85 v/v) was developed as it was showing good peak shapes and a significant amount of resolution. The mobile phase was flowed at 1.2 ml/min with detection of BEN analytes at 236 nm and MET analytes at 225 nm respectively. Result: Method development was done. Specificity, linearity, accuracy, precision, robustness, limit of detection and limit of quantitation were used to accomplish validation. The method was found linear from 32.5 – 500 µg.ml-1 for both BEN and MET individually. The percentage recovery of BEN when placed for period of 12 hours was found to 100% in 0.1N/M NaOH at 60˚C and Thermal (60˚C); 12 % degradation in 0.1N/M HCl at 60˚C; Oxidation (3-6% H2O2) at room temperature whereas for MET was 100 % in 0.1N/M NaOH, 0.1N/M HCl at 60˚C, at thermal (60˚C) as well as oxidation by 3-6% H2O2 at room temperature.  Conclusion: Developed analytical method for the simultaneous estimation of Benidipine (BED) and Metoprolol (MET) in both bulk and tablet formulation has obliged the ICH guidelines including, tailing factor (T), separation factors (α), theoretical plates (N), capacity factor (k’), resolution (R) and RSD (%). The validated stress degradation studies under thermal, oxidative, alkali and acid ascertained few degradation products for Benidipine whereas the Metoprolol was unaffected with forced degradation studies. Keywords: Benidipine, Metoprolol, Reverse-Phase High Performance Liquid Chromatography, Stability indicating method