Ann Reese Comfort

Intelligent Materials for Controlled Release

This volume examines recent developments in the use of intelligent materials and systems for drug delivery. Controlled release technology is moving from being a simple carrier of active agents to becoming a powerful and flexible method that permits subtle modulation of the delivery profile based on the needs of the biological host. The chapters collected here cover recent advances in materials with responsive properties, novel concepts in controlled release technology, new applications, and microanalytical techniques for rapid and accurate measurements of small samples.

Enhanced transport in a therapeutic transdermal system.

Ethanol was incorporated into a transdermal therapeutic device to enable the controlled delivery of enhancer and drug to the skin surface. A variety of control membrane laminates were examined for swelling and adhesion strength following equilibration with ethanolic solutions to identify a mechanically stable control membrane laminate. In vitro skin permeation analysis of the control membrane laminate showed that ethanol flux was linearly related to the ethanol volume fraction. A reservoir-type therapeutic transdermal system incorporating ethanol was developed to provide constant release of drug and ethanol through skin for 24 h. In vitro ethanol skin permeation rates were constant for 24 h and adhesion was stable over 16 wk at 40 degrees C using a transdermal reservoir device.

Correlation and Prediction of Moisture-Mediated Dissolution Stability for Benazepril Hydrochloride Tablets

AbstractPurpose. This report investigated dissolution stability of benazepril hydrochloride tablets. Methods. Reduction in dissolution rate was observed for benazepril hydrochloride tablets when they were subjected to stressed storage condition (40°C/75% RH) for prolonged periods of time (1-3 months). Moisture contents of initial and stressed tablets were measured by Karl Fischer method. Comparative thermal and physical characterizations of initial and stressed tablets were also performed. A mathematical model that was used to predict possible reduction in dissolution rate was proposed and validated using experimental data. Results. It was found that there was a direct correlation between moisture content of benazepril hydrochloride tablets and their percentage of dissolution at 10 min. At moisture content below 3.5%, there were no significant changes in dissolution values. Beyond that point, however, a close to linear decrease in dissolution was observed as a function of increase in moisture content. Results from thermal and X-ray analysis have ruled out possible changes in drug substance. Other physical characterization, such as scanning electron microscope and mercury porosimetry measurements, revealed changes in core structure of stressed tablets vs. initial tablets. Based on results from these measurements, “preactivation” of disintegrant was identified as the mechanism for reduction in dissolution rate above critical moisture content. A simple physical model for moisture uptake of benazepril hydrochloride tablets was also proposed for predicting when, based on water vapor transmission and critical moisture content, dissolution rate will decline. Conclusions. Physical changes of tablets mediated by moisture were the main cause for reduction in dissolution. Inclusion of desiccant, although beneficial, cannot prevent reduction in dissolution completely. The simple physical model proposed in this report was found to be useful in predicting the dissolution stability of the dosage form.

Temporally controlled transdermal system: biphasic transdermal delivery of nitroglycerin

Abstract A novel biphasic transdermal drug delivery system was developed to provide a technology of varying the temporal rate of the drug input to optimize the chronopharmacological response. The biphasic profile of a drug across skin was obtained by using a permeation enhancer to provide a high initial flux, and a subsequently lower flux by the rapid depletion of the enhancer from a finite volume reservoir. A pseudo-steady-state model was developed to guide the formulation and the design of this system. The performance of a nitroglycerin biphasic transdermal system was demonstrated in vitro, using aqueous ethanol as an enhancer.

In vitro characterization of a solvent-controlled nitroglycerin transdermal system

A well-controlled solvent-based system for transdermal delivery of nitroglycerin has been developed. This system is fully characterized with respect to the effect of ethanol and nitroglycerin concentration in the reservoir on the steady-state flux profile in vitro. The nitroglycerin flux and ethanol flux through the system and skin are linearly proportional to the ethanol concentration in the donor compartment of the system. The ethanol volume fraction in the donor controls the permeability of the CML/skin laminate. As ethanol concentration controls the flux of nitroglycerin from the system through skin, it is possible to reduce intersubject variation in nitroglycerin transdermal delivery through the transdermal system design.