Application Of Transdermal Delivery System Research Articles

Measuring Adhesive Performance in Transdermal Delivery Systems

The therapeutic performance of a transdermal delivery system (TDS) can be affected by the quality of contact between the patch and the skin. The adhesion of a TDS to the skin is obtained by using pressure-sensitive adhesives (PSAs), which are defined as adhesives capable of bonding to surfaces with the application of light pressure. The adhesive properties of a TDS can only be fully and correctly characterized by considering the following factors: (i) the property that enables an adhesive to form a bond with the surface of another material upon brief contact and under light pressure (tack); (ii) the resistance of the matrix to flow that could be considered as an expression of the cohesiveness of the matrix itself (creep resistance); and (iii) the force required to peel away a patch from a surface (peel adhesion). In this paper, attention is focused on the most widely used methods for the measurement of TDS adhesive properties in development studies and in the quality control of TDSs. The most critical formulative variables in the development of TDSs are the type and concentration of additives used, the drug loaded, the PSA thickness, the composition and thickness of the backing layer, and the solvent residue. There is a lack of evidence for a relationship between the results obtained in in vitro adhesion tests and the in vivo adhesion performance of TDSs. Therefore, an analysis of the percentage of TDSs that lifted and/or detached during pharmacokinetic and clinical studies should be performed during development studies. No official tests for adhesive strength are currently included in the TDS monographs of the most authoritative pharmacopeias. At present, the medical application of TDS relies on tests standardized by the adhesive tape industry or prescribed in the adhesive tape monographs of US and Japanese Pharmacopoeias, or adaptations of these. The development of new methods is recommended to meet the specific requirements of evaluating TDSs, and to improve the correlation between in vitro tests and in vivo performance.

Pharmacokinetics of a 7‐Day 17β‐Estradiol Transdermal Delivery System: Effect of Application Site and Repeated Applications on Serum Concentrations of Estradiol and Estrone

FemPatch (Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI), a new 7-day 17 beta-estradiol transdermal delivery system (TDS), has been developed for treatment of menopausal vasomotor symptoms. This two-period crossover study was conducted to determine the effects of TDS application site (buttocks versus abdomen) and early TDS replacement on estradiol and estrone concentrations, and to quantify intersubject and intrasubject pharmacokinetic variability. Eighteen healthy, postmenopausal female volunteers received a single 7-day TDS application to the abdomen and repeated TDS applications to the buttocks (regular replacement on days 7 and 14, intentional early replacement on day 17, and removal on day 21). Serial serum samples were assayed for estradiol and estrone by validated radioimmunoassay methods. The 7-day TDS delivers estradiol at a constant, near zero-order rate for the duration of application, independent of application site. Mean serum estradiol concentrations were higher after application to the buttocks than after application to the abdomen (19 and 15 pg/mL above baseline, respectively), making the buttocks the preferred site for TDS application. Mean serum concentration of estradiol was slightly higher (23 pg/mL above baseline) for the treatment week with early TDS replacement due to the transient increase in concentration over the first 24 hours after replacement. Parallel but smaller increases in concentrations of estrone were observed. Serum estradiol and estrone concentrations are reproducible within an individual from application to application (coefficient of variation, 25%). Variability between individuals was higher (coefficient of variation, 40-50%).

CHARACTERIZATION OF A 7 DAY 17β-ESTRADIOL TRANSDERMAL DELIVERY SYSTEM: PHARMACOKINETICS IN HEALTHY POSTMENOPAUSAL WOMEN

To assess the delivery characteristics of a new 7 day 17 beta-estradiol transdermal delivery system (TDS), estradiol and estrone pharmacokinetics were evaluated following a single 7 d application of one TDS or two TDSs in 24 healthy, postmenopausal women in a nonblind, randomized, two-period crossover study. Serial blood samples and total urine output were collected before (baseline measurement of endogenous hormone) and during TDS application, and for 24 h (urine) or 72 h (blood) following TDS removal. Serum was assayed for estradiol and estrone by a validated radioimmunoassay (RIA) method. The combined amounts of estradiol and its conjugates, and estrone and its conjugates in urine were determined by validated RIA methods. Overall, one or two estradiol TDSs were well tolerated by healthy, postmenopausal female volunteers. Estradiol absorption from the TDS was characterized by a zero-order process and was dose proportional, resulting in average steady-state serum estradiol concentrations of 16 and 33 pg mL-1 above baseline during the 7 d application of one and two TDSs, respectively. Parallel but smaller increases in serum estrone concentrations were observed, resulting in an increase in the serum estradiol/estrone concentration ratio from approximately 0.2 at baseline to median values of 0.64 and 0.88 during application of one and two TDSs, respectively. The 7 day 17 beta-estradiol TDS delivered a nominal estradiol dose of 0.02 mg/24 h during the intended wear period.

Haemodynamic effects of glyceryl trinitrate following repeated application of a transdermal delivery system with a phasic release profile

The haemodynamic effects and plasma concentrations of glyceryl trinitrate (GTN) and its dinitrate metabolites were investigated in 8 healthy male volunteers during 5 days of application of a new transdermal delivery system (TDS) with time-dependent release characteristics, which were considered to prevent or to diminish development of nitrate tolerance. On the first and fifth day of administration the following haemodynamic parameters were determined: digital pulse ratio of height of systolic peak to height of dicrotic wave (i.e. a/b-ratio), heart rate and systolic blood pressure under orthostatic conditions. Peak plasma concentrations of GTN were 139 and 155 pg.ml-1 on the first and fifth day of treatment, and the corresponding trough concentrations (i.e. 24 h after administration) were 52.5 and 36.6 pg.ml-1, respectively. Compared to placebo, the area under the effect curve of the a/b-ratio of the digital pulse was increased on the first (25.6%) and fifth day (13%). A significant increase of heart rate and a decrease of systolic blood pressure were seen only on the first day of treatment. The haemodynamic effects of sublingual GTN 0.8 mg were reduced by 69% (a/b-ratio) and 52% (standing heart rate) on the fifth day compared to the pretreatment values. Thus, the phasic release of GTN from the new TDS can be demonstrated by the time course of the plasma concentrations of GTN and its metabolites. Nevertheless, following repeated administration the hemodynamic effects are blunted.