The enhancing effect of supersaturation generated by amorphous ketotifen in silicone pressure-sensitive adhesive matrices (PSA) on the transdermal absorption was evaluated in vivo using hairless rats, and it was compared with the increase of drug amount in skin tissues. The duration of the enhancing effect was also investigated in relation to the time how long supersaturation was maintained in PSA. PSA containing crystalline ketotifen (PSA-Crystalline) and that containing amorphous ketotifen (PSA-Amorphous) were prepared by the solvent casting method using n-hexane and dichloromethane, respectively. In vivo transdermal absorption was evaluated by measuring the amount of ketotifen in PSAs, the stratum corneum, and viable skin tissues after administration of PSAs on abdominal sites of hairless rats. The amount of ketotifen absorbed into the systemic circulation was calculated by subtracting the drug amount in whole skin tissues from the amount of the drug released from PSAs, then it was monitored for up to 23h. In both types of PSA, a constant absorption rate was maintained for up to 23h after 7-h lag time. The enhancement factor of PSA-Amorphous against PSA-Crystalline was approximately 7, which was in good agreement with the difference of drug amount in viable skin tissues. Time course of the drug amount in PSA-Amorphous suggested that the supersaturated level was gradually decreased after 10h, but the decline of the driving force from PSAs was supplemented by the drug release from the skin depot resulting in the constant absorption rate up to 23h. These results suggest the usefulness of amorphous ketotifen to obtain enhanced transdermal absorption.
Available online 6 June 2013
Source:Current Opinion in Chemical Biology Author(s): Rita L Strack , Samie R Jaffrey Tools to study the abundance, distribution, and flux of intracellular molecules are crucial for understanding cellular signaling and physiology. Altho ... more
Available online 3 June 2013
Source:Current Opinion in Chemical Biology Author(s): Yuichiro Hori , Kazuya Kikuchi Protein labeling by using a protein tag and its specific fluorescent probe is increasingly becoming a useful technique for the real-time imaging of pro ... more
The average 5-year survival for colorectal cancer (CRC) is less than 10% if metastasis occurs, but can reach 90% if detected early. A new non-invasive test has been developed that measures methylation of the SDC2 gene in tissues and blood sera. This test detected 87% of all stages of colore ... more
Regular marijuana use is associated with favorable indices related to diabetic control, say investigators. They found that current marijuana users had significantly lower fasting insulin and were less likely to be insulin resistant, even after excluding patients with a diagnosis of diabetes ... more
Most children who suffer from sports-related concussions recover within a few days. However, in a small number of children, symptoms can last for a month or more. Although there have been numerous theories as to what might predict a longer recovery time, there is no definitive answer as to ... more