Mebeverine decreases mass movements and stool frequency in lactulose-induced diarrhoea.

BACKGROUND: In spite of its frequent use in the treatment of irritable bowel disease little is known about mebeverine's mode of action in man. AIM: To examine mebeverine's effect on transit though the gut during lactulose-induced diarrhoea. METHODS: Nine healthy volunteers undertook a two-way randomized crossover study. Diarrhoea was induced using lactulose pre-treatment (20 m t.d.s., 4 days) and subjects received either mebeverine (135 mg t.d.s.) or no treatment. Transit of two enteric-coated capsules containing radiolabelled 8.4 mm tablets and 180-250 microM ion exchange resin were followed using gamma scintigraphy. Stool frequency and symptoms were assessed by diary cards. RESULTS: Mebeverine reduced mean daily stool frequency associated with lactulose ingestion from a median of 2.25 (interquartile range (IQR) 1.75-2.75) to 1.5 (IQR 1.25-2.25) movements. Mebeverine significantly reduced the number of mass movements observed in the colon during the 11 h of the study from 2 (2-2) to 1 (1-2), and the number of retrograde movements from 1 (0-2) to 0 (0-0) (P < 0.05). Mebeverine did not significantly alter the gastric emptying rate of the intact capsule (2.9 (1.9-3.2) to 2.8 (2.6-4.0) h) however it induced a small but significant acceleration in small intestinal transit of the capsule (1.6 (0.8-2.0) h to 1.0 (0.52-1.32) h, P=0.02). CONCLUSION: Mebeverine reduces the diarrhoeal effect of lactulose by decreasing the mass movements induced in the ascending colon. This effect may contribute to its clinical effect in irritable bowel syndrome.

Quantitative, noninvasive assessment of antidiarrheal actions of codeine using an experimental model of diarrhea in man.

Enteric coating of a capsule has been used to deliver a bolus of radioisotope to the ileocecal region. This has allowed quantitative assessment of regional colonic transit in a group of healthy subjects whose proximal colonic transit was accelerated by lactulose 20 ml thrice daily. In this experimental model of diarrhea, codeine delayed transit from mouth to terminal ileum and also delayed transit through the ascending colon from 5.3 +/- 2.5 hr to 7.4 +/- 2.5 hr, N = 11, P < 0.05. Furthermore, codeine delayed whole colon transit, as assessed by geometric center analysis, which showed the delay to be most marked in the right colon with little effect noted in the left colon. In addition, codeine significantly reduced the number of retrograde movements observed and reduced the colonic response to eating. The antidiarrheal effect of codeine appears to be due to a combination of delayed mouth-cecum transit plus an additional delay in the ascending colon. This colonic delay may be partially explained by a reduction in postprandial propulsive movements that were seen in this model of diarrhea.

Scintigraphic demonstration of lactulose-induced accelerated proximal colon transit.

Although lactulose, a widely used cathartic, is known to increase stool frequency, details of its site of action in the colon are obscure. In the present study a noninvasive scintigraphic technique was used to closely follow the movements of proximal colonic contents. Lactulose, 10-20 mL three times daily, significantly accelerated mean transit through the ascending colon from 12.9 +/- 3.7 to 7.0 +/- 2.5 hours (n = 11; P less than 0.01). This was associated with the occurrence of mass movements, with six such events seen during lactulose treatment whereas only one was seen during the control study (P less than 0.05). Lactulose also accelerated movement through the rest of the colon so that at 24 hours after dosing the geometric center of the isotope bolus was distal to that seen during the control study (6.6 +/- 1.2 vs. 4.7 +/- 1.3; n = 11, P less than 0.001). This model of diarrhea in otherwise normal subjects was subsequently used to study the effects of viscous gels in diarrhea. The viscous and relatively poorly fermented gel ispaghula, 3.5 g three times daily, abolished mass movements and was associated with a small but significant increase in proximal colonic transit time, which increased from 6.1 +/- 2.1 to 7.7 +/- 1.5 hours (n = 8; P less than 0.05). By contrast, the viscous but readily fermentable gelling agent guar gum, 5 g three times daily, further accelerated the cathartic effect of lactulose, with the mean transit time decreasing from 6.4 +/- 2.3 to 4.7 +/- 1.7 hours (n = 8; P less than 0.05). The acceleration of proximal colonic transit by lactulose may be a useful model to study diarrhea and its modification by therapy.

Fourier transform-Raman spectroscopy for the qualitative and quantitative characterization of sulfasalazine-containing polymeric microspheres.

FT-Raman spectroscopy (FTRS) has been used to characterize microspheres produced from the pharmaceutical polymer Eudragit RS containing a range of concentrations of the drug sulfasalazine. While pure sulfasalazine produced an intense and complex Raman spectrum, the spectrum of drug-free Eudragit RS microspheres was considerably weaker in intensity and contained only a few prominent Raman scattering peaks. In spectra of the drug-polymer microspheres, peaks arising from the individual components could be identified. This enabled a quantitative analysis to be undertaken by calculating the ratio between the area of a sulfasalazine peak and the area of a Eudragit RS peak for each microsphere spectrum. A correlation was shown between the peak area ratio and the microsphere sulfasalazine content. FTRS was then applied to a series of microsphere samples which had been dissoluted into pH 7 buffer for 1, 3, 6, 9, 12, or 24 hr. For each spectrum, the drug-polymer peak area ratio was determined and this in turn enabled calculation of the residual drug content of the microsphere sample. FTRS-calculated data showed good agreement with microsphere drug content values determined spectrophotometrically.

Microencapsulation using emulsification/solvent evaporation: an overview of techniques and applications.

This review describes the microencapsulation of pharmaceuticals using the technique of emulsification-solvent evaporation. Guidelines are given for development of encapsulation processes for drugs with either high or low aqueous solubilities. Methods for microsphere characterization and assessment are detailed. The properties of a range of encapsulating polymers are described with examples of drugs encapsulated. The article concludes by speculating the clinical potential of microsphere-based drug delivery systems.