Skin Permeation of Rosiglitazone from Transdermal Matrix Patches - Pharmaceutical Technology

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Skin Permeation of Rosiglitazone from Transdermal Matrix Patches
The authors demonstrate that sustained-release delivery can help avoid the risk of sudden higher-blood concentration of a drug to avoid toxicity.


Pharmaceutical Technology
Volume 34, Issue 5, pp. 56-72

Results and discussion

Pressure-sensitive Duro-Tak adhesives are generally tacky, which enables them to adhere to the skin with gentle pressure upon application. A good pressure-sensitive adhesive for TDDS can be removed from the skin without leaving a residue (13, 19, 20). Duro-Tak 387-2516 and Duro-Tak 87-2852, in ratios of 4:5 and 4:6, respectively, were selected for formulations because the mixtures had acceptable tackiness and were easily removed without leaving residue on the skin.


Figure 3
A drug–excipient interaction study is an important preformulation study (21). Fourier transform IR (FTIR) spectroscopy has been widely used to identify the interactions between drug and excipient molecules at the level of functional groups. The authors evaluated drug–polymer interaction by analyzing the FTIR spectroscopic data. Figure 3A depicts the spectrum of pure drug rosiglitazone maleate. Figure 3B shows the spectrum of a blend of polymers, Duro-Tak 387-2516 and Duro-Tak 87-2852, in a ratio of 4:5. Figure 3(c) shows the spectrum of drug with a blend of the same polymers in a ratio of 4:5. The figures reveal the absence of a predominant variation in the IR spectra of drug in the Duro-Tak mixture [see Figure 3(c)] compared with those of the drug alone [see Figure 3(a)]. Minor changes in the peaks, mainly between 1500 and 400 cm–1, could result from the formation of weak bonding such as hydrogen bonding, dipole moment, or bond formation resulting from van der Waals force. The depicted region provides the typical IR absorption frequencies that result from stretching vibrations of the functional groups such as weak –CH2, out-of-plane bending of –CH=CH2, out-of-plane –OH bending, –NH2 and –N–H wagging, and the =CO group. Many of these groups are present both in the drugs and the polymers. Therefore, weak physical bonds may have formed because no major shifting of the peaks was noted.


Figure 4
The surface morphology of the patches and the dorsal and ventral surfaces of the skin samples, before the in vitro skin-permeation study and 50 h after the in vitro skin-permeation study, were scanned with an SEM. Figure 4(a) shows the external morphology of a patch before the in vitro skin permeation. Figure 4(b) shows the external morphology of the patch 50 h after in vitro drug-permeation studies. Figure 4(a) shows drug distribution in a transdermal patch. Figure 4(b) shows several drug particles, both large and small, that were not released. Figure 4(a) shows that the drug distribution was in clusters. Figure 4(b) shows small, holelike structures present on the matrix along with the drug clusters. The holes were probably to the result of the release of drug from the matrices. Furthermore, after 50 h of drug release, patches maintained their structure. The SEM of the morphology of the dorsal surface of the skin before permeation, and the morphology of the dorsal surface of the skin 50 h after in vitro drug permeation, did not vary. The same was true for the SEM of the ventral surfaces taken before permeation and 50 h after permeation study.

Various physiochemical tests were conducted, including the average thickness, the mean area of the patches, their moisture content, and moisture uptake capabilities.

The patches (i.e., Formulations I and II) were circular with an average diameter of 2.37 0.04 cm (mean SD, n = 10) and had a mean area of 4.41 0.17 cm2 (mean SD, n = 10).

The mean thicknesses of the backing membrane, whole patch, and the drug–polymer matrix are shown in Table I. Thin patches were developed. However, Formulation I was thinner than Formulation II. That discrepancy may arise from their different polymeric-blend ratios.

The average percent moisture content of the formulations I and II were 2.13 0.09% and 2.55 0.13% (mean SD, n = 10) respectively. Low moisture content in the patches prevents them from forming a dry and brittle film (22).

For in vitro skin-permeation studies, various media such as normal saline, phosphate buffer, and 20% PEG 400 in normal saline were used (10, 12, 14 and 23). Of the media, 20% v/v in normal saline provided biphasic characteristics of in vitro receptor fluid, which is believed to be one of the best media for studying the in vitro skin permeation of a drug (12). The solubility of rosiglitazone maleate in 20% v/v PEG 400 in normal saline was 14.15 mg of the drug dissolved per mL of the media. This result indicated that 20% v/v PEG 400 in normal saline is suitable for in vitro release and skin-permeation studies of the drug.


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