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

Methods

Drug-solubility study. Various percentages (10%, 20%, 30%, 40% v/v) of polyethylene glycol (PEG) in a normal saline or phosphate buffer have been reported as receptor fluids to study the skin permeation of drugs (10, 11). The mixtures provide biphasic characteristics of the sebum–sweat mixture, the main fluid responsible for in vivo skin permeation (12). The authors selected 20% v/v PEG in normal saline as a receptor fluid. The solubility of the drug in 20% v/v PEG in normal saline was determined by adding an excess amount (1 g) of drug in 2 mL of solvent mixture and keeping the flask containing the solution on a mechanical shaker for 24 h at 25 C (13). These parameters were enough to provide a saturated solution of the drug. After 24 h, the solutions were transferred into test tubes and centrifuged at 2000 rpm for 30 min at room temperature. The solutions in the test tubes were allowed to stand for 30 min, and 1 mL of supernatant liquid was placed in a 100-mL volumetric flask and diluted with 100 mL of the solvent mixture (20% v/v PEG 400 in normal saline). After thorough mixing for 5 min, 5 mL solution from each volumetric flask was mixed with 5 mL of solvent mixture in a test tube. The mixture was filtered, and the absorbance was read at 318 nm with an ultraviolet–visible spectrophotometer (Genesys Thermoelectocorporation, Madison, WI) against a blank. The amount of drug dissolved was quantified from the calibration curve prepared previously.

Preparation of the patch. To prepare the backing membrane, polyvinyl alcohol (6% w/v) was added to warm (about 40 C) double-distilled water, and the mixture was constantly stirred on a magnetic stirrer at 60 C for 15–20 min to attain a homogeneous solution; 3 mL of homogeneous solution was then poured into hollow, glass, cylindrical mold (4 cm in height and 2.55 cm in internal diameter) on the end wrapped with aluminum foil. A smooth, uniform, transparent backing membrane was obtained after keeping the mold at 60 C for 24 h (14). Backing membranes were removed from some of the molds, and their individual thicknesses were determined.


Table I: Ingredients and mean thickness of formulation I and II
Initially, various combinations of the polymers were screened to prepare patches to achieve the appropriate consistency and physicochemical properties. The best two prepared formulations, in terms of the criteria mentioned above, are reported here. Blends of Duro-Tak 387-2516 and Duro-Tak 87-2852 were prepared in the volume ratio of 4:5 and 4:6, respectively, by dissolving the respective polymer mixtures in the appropriate volume ratios separately in solvent mixtures consisting of ethyl acetate, isopropyl alcohol, toluene, and n-hexane (12:6:1:1) (14). The volume ratio of the polymers and the solvents was 1:2. A homogeneous solution was made using a magnetic stirrer and a magnetic bead. For each patch, a separate mixture was prepared. Rosiglitazone maleate (12 mg per patch for all experiments other than the antidiabetic study in animals, which used 4-mg patches) was added to each mixture and stirred for 20 min until a homogeneous suspension was obtained; 3 mL of the homogeneous suspension was then cast on the prepared backing membrane and dried at room temperature for 24 h, which yielded a medicated matrix patch of rosiglitazone maleate (see Table I).

Patch evaluation and characterization. Drug–excipient interaction. Infrared (IR) spectroscopy (Magna IR 750 series ll, Nicolet, Madison, WI) was carried out for a blend of Duro-Tak 387-2516 and Duro-Tak 87-2852, and for the mixture of drug and polymers. All three samples were placed between disks of sodium chloride windows and scanned over the region of –4000–400 cm–1. Spectra were compared from computer-data sheets manually, and data were interpreted.


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