Enhancement of transdermal permeation of carvedilol by sonophoresis technique: In vitro evaluation.

In this study, various matrix type transdermal patches containing carvedilol of variable combination of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) were prepared by solvent evaporation technique. The patches were prepared by adding surfactant (sodium lauryl sulphate) to promote drug penetration which was found to increase transdermal transport. Therapeutic frequency ultrasound (1 MHz) and surfactant have been individually shown to enhance transdermal drug transport. In this study, we investigated the synergistic effect of ultrasound and surfactants on transdermal drug delivery. This study provides an investigation of the dependence of therapeutic-frequency sonophoresis on various ultrasound parameters, including ultrasound pretreatment time and the distance of the horn from the skin. Based on the in vitro release and in vitro permeation profile the formulation Fs1 (PVP/EC 1:2) shows the best release. Ultrasound was applied to pretreat the skin using a sonicator operating at a frequency of 1 MHz at an intensity 2 Watts/cm2. The optimum ultrasonication time of 50 min at a distance of 1 cm shows the best release. The skin conductivity enhancement was found to be inversely proportional to the distance of horn from the skin and it is directly proportional to ultrasonication pretreatment time. These findings will be useful in optimizing therapeutic-frequency sonophoresis.

Effect of red chillies on small bowel and colonic transit and rectal sensitivity in men with irritable bowel syndrome.

BACKGROUND: Altered motility and threshold for pain have been incriminated in the pathogenesis of the irritable bowel syndrome (IBS). Capsaicin affects visceral sensory perception and chillies, which contain capsaicin, have been shown to accelerate gut transit. AIMS: To evaluate the effect of red chillies on small bowel transit (SBT) and colonic transit (CT) and rectal sensitivity in normal men and men with IBS. METHODS: Twenty-nine men with IBS diagnosed using Manning's criteria, and 21 healthy men, were studied before and after ingestion of 10 g red chilli powder (capsaicin equivalent 14 mg). SBT time was measured as the time taken for 99mTc-sulfur colloid to reach the cecum after leaving the stomach. Total and segmental CT times were assessed using radio-opaque markers. Rectal sensitivity and pain threshold to intrarectal balloon distension were measured. RESULTS: The median (range) bowel frequency in patients and healthy men was 2 (1-6) and 1 (1-3) per day (p=0.03), respectively. After ingestion of chillies, it increased to 3 (1-8) per day and 2 (1-4) per day (p=0.01), respectively. There was no difference in transit times between patients and healthy men; chilli ingestion did not alter SBT time, total or segmental CT time. IBS patients had a lower threshold to balloon distension for both discomfort and pain in the basal state (p<0.01). Chillies increased this threshold in healthy men (p<0.01). CONCLUSIONS: Men with IBS do not have SBT or CT abnormalities, but have a lower rectal balloon sensitivity threshold. Chilli powder does not alter either SBT or CT in men with IBS or healthy men; however, it increases the rectal threshold for pain in the latter.