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d-limonene, a terpene and natural compound, has been found to be an excellent penetration enhancer for transdermal drug delivery (TDD). It hence has been incorporated within various transdermal formulations. Herein, we report the application of polystyrene gel swollen with d-limonene and its derivatives for TDD. Poly(styrene- co -divinylbenzene) (PS gel), poly(styrene- co -divinylbenzene- co -4-vinylpyridine) (PS-4VP) gel and poly(styrene- co -divinylbenzene- co -(vinylbenzyl) trimethylammonium chloride) (PS-VBAC gel) were employed as chemical gels to improve the stability of the TDD substrates. The drug permeation properties from the PS gels swollen in limonene were examined, regarding the effect of its network density as well as their rheological properties. The lowest density of the network showed the highest steady flux of the permeation at 43.7 ± 0.3 μg/cm². FT-IR spectra were confirmed for PS-4VP and PS-VBAC, bearing cationic moieties and they could control the release of ibuprofen by the electrostatic interaction at the interface of organogel and skin. The steady state flux of skin permeation got low values from 55.2 ± 0.8 to 11.6 ± 2.0 μg/cm², when the cationic moieties were increased. Moreover, the chemical network of PS gel swollen in limonene showed high mechanical stability illustrated by elastic modulus (G') of about 98 kPa for 10% cross-linked PS gel. The developed PS gels swollen in limonene show highly promising results, suggesting their possible application in TDD.

Cationic Moieties in Polystyrene Gels Swollen with d-Limonene Improved Transdermal Delivery System