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Profiling of drug crystallization in the skin

Goh CF, Boyd BJ, Craig DQM, Lane ME

Expert Opin Drug Deliv, 2020 09;17(9):1321-1334.
PMID: 32634033 DOI: 10.1080/17425247.2020.1792440

BACKGROUND: Drug crystallization following application of transdermal and topical formulations may potentially compromise the delivery of drugs to the skin. This phenomenon was found to be limited to the superficial layers of the stratum corneum (~7 µm) in our recent reports and tape stripping of the skin samples was necessary. It remains a significant challenge to profile drug crystallization in situ without damaging the skin samples.
METHODS: This work reports the application of an X-ray microbeam via synchrotron SAXS/WAXS analysis to monitor drug crystallization in the skin, especially in the deeper skin layers. Confocal Raman spectroscopy (CRS) was employed to examine drug distribution in the skin to complement the detection of drug crystallization using SAXS/WAXS analysis.
RESULTS: Following application of saturated drug solutions (ibuprofen, diclofenac acid, and salts), CRS depth profiles confirmed that the drugs generally were delivered to a depth of ~15 - 20 µm in the skin. This was compared with the WAXS profiles that measured drug crystal diffraction at a depth of up to ~25 µm of the skin.
CONCLUSION: This study demonstrates the potential of synchrotron SAXS/WAXS analysis for profiling of drug crystallization in situ in the deeper skin layers without pre-treatment for the skin samples. [Figure: see text].

Matched MeSH terms: Diclofenac/metabolism*
Formulation variables affecting drug release from xanthan gum matrices at laboratory scale and pilot scale

Billa N, Yuen KH

AAPS PharmSciTech, 2000;1(4):E30.
PMID: 14727895

The purpose of this research was to study processing variables at the laboratory and pilot scales that can affect hydration rates of xanthan gum matrices containing diclofenac sodium and the rate of drug release. Tablets from the laboratory scale and pilot scale proceedings were made by wet granulation. Swelling indices of xanthan gum formulations prepared with different amounts of water were measured in water under a magnifying lens. Granules were thermally treated in an oven at 60 degrees C, 70 degrees C, and 80 degrees C to study the effects of elevated temperatures on drug release from xanthan gum matrices. Granules from the pilot scale formulations were bulkier compared to their laboratory scale counterparts, resulting in more porous, softer tablets. Drug release was linear from xanthan gum matrices prepared at the laboratory scale and pilot scales; however, release was faster from the pilot scales. Thermal treatment of the granules did not affect the swelling index and rate of drug release from tablets in both the pilot and laboratory scale proceedings. On the other hand, the release from both proceedings was affected by the amount of water used for granulation and the speed of the impeller during granulation. The data suggest that processing variables that affect the degree of wetness during granulation, such as increase in impeller speed and increase in amount of water used for granulation, also may affect the swelling index of xanthan gum matrices and therefore the rate of drug release.

Matched MeSH terms: Diclofenac/metabolism

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