Cyclodextrin-crosslinked poly(acrylic acid): Adhesion and controlled release of diflunisal and fluconazole from solid dosage forms

The controlled release of diflunisal and fluconazole from tablets made of novel polymers, poly(acrylic acid) (PAA) crosslinked with either β-cyclodextrin (βCD) or hydroxypropyl-βCD (HPβCD), was investigated and Carbopol 934P (Carbopol) was used as a highly crosslinked PAA for comparison. Diflunisal strongly associates with βCD-PAA and HPβCD-PAA polymers (Ka of 486 and 6,055 M(-1) respectively); thus, it was physically mixed into the conjugates and also precomplexed to identify whether decomplexation has any influence on release kinetics. Fluconazole has poor complexing ability (Ka of 34 M(-1) with HPβCD-PAA); thus, it was only tested as a physical mixture. Swelling and adhesion studies were conducted on all tablet combinations and adhesivity of the CD-PAA polymer tablets was maintained. Diflunisal release was much slower from HPβCD-PAA tablets than from βCD-PAA, suggesting that a higher degree of complexation retards release. The precomplexed diflunisal release was also slower than the physically mixed diflunisal of the corresponding conjugate. The release closely followed zero-order kinetics for HPβCD-PAA, but was more sigmoidal for βCD-PAA and especially Carbopol. Conversely, poorly associating fluconazole released in almost exactly the same way across both polymers and Carbopol, indicating that the release kinetics of poorly associating drugs are not influenced by the presence of cyclodextrins. In view of the varying profiles and release rates shown with diflunisal for the different polymers, the fluconazole data support the concept that adequate complexation can indeed modulate the release kinetics of drugs.Marguerite J. Kutyła, Michael W. Boehm, Jason R. Stokes, P. Nicholas Shaw, Nigel M. Davies, Ross P. McGeary, Jonathan Tuke, and Benjamin P. Ros

Binary mixtures of two anionic polysaccharides simulating the rheological properties of oxidised starch

Modifications of starches are carried out to improve their industrial usefulness. However, the consumers prefer natural products. For this reason, various methods of starch properties modification are applied to replace those requiring the use of chemical reagents. The aim of this study was to determine whether it is possible to use binary pastes, containing normal potato starch and xanthan gum, as substitutes of chemically modified starches (with oxidised starch E 1404 pastes as an example). Flow curves with hysteresis loops, apparent viscosity at constant shear rate of 50 s-1 and in-shear structural recovery test with pre-shearing were applied to study the rheological properties of the pastes. It was found that two anionic hydrocolloids, potato starch and xanthan gum, can form binary systems with thickening properties, provided that their proportions are adequately adjusted. Some of the binary pastes under investigation exhibited rheological properties resembling pastes of starch oxidised with hypochlorite (E 1404). The way of tailoring the binary pastes properties is presented

The validity of a new structured assessment of gastrointestinal symptoms scale (SAGIS) for evaluating symptoms in the clinical setting

Background: The clinical assessments of patients with gastrointestinal symptoms can be time-consuming, and the symptoms captured during the consultation may be influenced by a variety of patient and non-patient factors. To facilitate standardized symptom assessment in the routine clinical setting, we developed the Structured Assessment of Gastrointestinal Symptom (SAGIS) instrument to precisely characterize symptoms in a routine clinical setting. Aims: We aimed to validate SAGIS including its reliability, construct and discriminant validity, and utility in the clinical setting. Methods: Development of the SAGIS consisted of initial interviews with patients referred for the diagnostic work-up of digestive symptoms and relevant complaints identified. The final instrument consisted of 22 items as well as questions on extra intestinal symptoms and was given to 1120 consecutive patients attending a gastroenterology clinic randomly split into derivation (n\ua0=\ua0596) and validation datasets (n\ua0=\ua0551). Discriminant validity along with test–retest reliability was assessed. The time taken to perform a clinical assessment with and without the SAGIS was recorded along with doctor satisfaction with this tool. Results: Exploratory factor analysis conducted on the derivation sample suggested five symptom constructs labeled as abdominal pain/discomfort (seven items), gastroesophageal reflux disease/regurgitation symptoms\ua0(four items), nausea/vomiting (three items), diarrhea/incontinence (five items), and difficult defecation and constipation (2 items). Confirmatory\ua0factor analysis conducted on the validation sample\ua0supported the initially developed five-factor\ua0measurement model (χ1932=892.2, p\ua

Erratum to: the validity of a new structured assessment of gastrointestinal symptoms scale (SAGIS) for evaluating symptoms in the clinical setting

The original version of this article unfortunately contained a mistake. There was a typo in coauthor name. It should be M. Kutyla; instead, it was received and published as M. Kutuyla. The original article has been corrected

Induction of meal-related symptoms as a novel mechanism of action of the duodenal-jejunal bypass sleeve

Background: Treatment with a duodenal-jejunal bypass sleeve (DJBS) induces clinically significant weight loss, but little is known about the mechanisms of action of this device. Aim: The aim of this study was to characterize the mechanisms of action of the DJBS and determine the durability of weight loss and metabolic improvements. Materials and Methods: We studied a cohort of 19 subjects with severe obesity and type 2 diabetes (baseline body mass index: 43.7±5.3 kg/m2). Anthropometry, body composition, blood pressure, biochemical measures, and dietary intake were monitored for 48 weeks after DJBS implantation, and then for 1 year after device removal. Gastric emptying and triglyceride absorption were measured at baseline, 8 weeks after implant, and within 3 weeks of device explant. Visceral sensory function was assessed at baseline, 4 weeks after implant, and within 3 weeks after explant. Results: Significant weight loss (