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.

Temporally controlled drug delivery systems: coupling of pH oscillators with membrane diffusion.

A novel approach to modulate the release of a drug or an active ingredient that avoids the need for external power sources or electronic controllers is described. By changing the pH of a solution relative to the pKa, a drug, enhancer, or solubilizer may be rendered charged or uncharged. Because only the uncharged form of a drug can permeate across lipophilic membranes, a temporally modulated delivery profile may be obtained with a pH oscillator in the donor solution. Ionizable permeants have a buffer capacity, so the feasibility of coupling the mixed Landoldt pH oscillator with membrane diffusion of nicotine or benzoic acid is demonstrated for a single oscillation.

Polymorphism of 17-beta estradiol in a transdermal drug delivery system.

The inclusions in a typical transdermal drug delivery system (TDS) containing estradiol drug were characterized using microscopic, spectroscopic and thermal analytical techniques. Optical and scanning electron microscopy were used to determine the locations and morphologies of the crystals in the matrix. Two different types of crystals randomly distributed laterally inside the patch were observed. Solid aggregates were found surrounding needle-like inclusions. Optical imaging through the thickness of the patch and SEM sections of the patch revealed that these inclusions were found to occupy a single layer inside the adhesive matrix. No inclusions were observed either in the backing-matrix interface or the matrix-liner interface. The inclusions exhibited a wide range of sizes. The thickness of the crystals as determined by SEM ranged from 10-14 microm. Out of the four crystal forms of estradiol, two of which are solvates (EA and EM) and the other two are anhydrous (EC and ED). Forms EC and ED did not exhibit significant differences in the spectra. Thermal analysis revealed that this was due to the highly unstable nature of ED and its tendency to either convert spontaneously to EC or occur in mixtures with it. The Raman spectrum of the aggregates in the patch showed peaks that seemed characteristic of at least two different forms of estradiol. Only one of these forms is a completely hydrogen bonded system and therefore, was concluded to be estradiol hemihydrate. A splitting of the C17-O peak at 1284 cm(-1) and 1294 cm(-1) was attributed to the existence of at least two types of crystal forms - one that exhibits hydrogen bonding and one that does not. DSC on different concentrations of estradiol in acrylic adhesive showed a clear endotherm for 14 wt % estradiol and apparent endotherms for lower concentrations. The absence of crystallization exotherms is due to the extremely slow kinetics of crystals growth in the polymeric patch.

Crystallization of beta-estradiol in an acrylic transdermal drug delivery system.

Transdermal drug delivery systems are pharmaceutical products that can deliver controlled doses of drugs from polymeric patches applied on the human skin. The long-term stability of these patches is a critical issue relative to their performance in delivering drugs at a constant rate. Where a drug has been dissolved in the polymeric adhesive patch, crystallization has been reported in several systems. This study uses a variety of characterization tools to determine the physical and chemical nature of the precipitates formed in situ in estradiol patches. Optical microscopy revealed that crystals were formed in a single layer inside the adhesive matrix and that there were two distinctly different morphologies: needle-like crystals and aggregates around the needles. From IR measurements it was evident that estradiol probably was present in more than one crystal form in these patches. Raman microscopy showed that the needle-like crystals contain the adhesive component and the aggregates some modified crystal form of estradiol, indicating that in addition to the drug, the polymeric adhesive also crystallizes during storage.