Journal
JOURNAL OF PHARMACEUTICAL INNOVATION
Volume 11, Issue 4, Pages 339-351Publisher
SPRINGER
DOI: 10.1007/s12247-016-9262-9
Keywords
Penetration enhancers; Diffusion; Viscoelasticity; Carbopol (R); Topical gels; Transcutol (R)-P; Propylene glycol; Ethanol
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The aim of this study was to investigate the effect of commonly used penetration enhancers on the viscoelastic properties and in vitro drug release from topical gel formulations. Three penetration enhancers, diethylene glycol monoethyl ether (Transcutol(A (R))-P, TC), propylene glycol (PG), and 70 % ethanol were selected in this study. The non-steroidal anti-inflammatory drug diclofenac sodium (DNa) was used as a model drug. DNa gels were prepared using the gelling agent Carbopol(A (R)) 971P with or without different concentrations of the three penetration enhancers. Each gel formulation was characterized in terms of its viscoelastic properties (elastic or storage modulus G' and viscous or loss modulus GaEuro(3)) using a controlled stress rheometer (CSR) and in vitro release using Franz diffusion cells. DNa gels containing TC, PG, and ethanol demonstrated a significant decrease in the viscoelastic properties compared to gels containing no penetration enhancers, and an enhancement in drug release. Gels containing TC at the highest tested concentration (40 %) exhibited the lowest viscoelastic properties and showed the highest enhancement in drug release. Both TC and ethanol showed a concentration-dependent effect in promoting steady-state flux values for DNa, unlike PG. DNa release kinetics from all gels followed super case II transport as fitted by the Korsmeyer-Peppas model. Our results provide valuable insights into the mechanisms by which different penetration enhancers can modulate drug release from topical gels by altering the rheological properties of the gelling agent.
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