Abstract
PurposeTopical nonsteroidal anti‐inflammatory drug formulations are used commonly to treat musculoskeletal pain and inflammation. Drug properties and formulation composition are the primary determinants of the transdermal drug delivery rate. The ex vivo transdermal flux through human skin of three topical diclofenac formulations was compared.MethodsThe formulations tested were hydrogel 1% diclofenac sodium and two emulsion gels (1.16%/2.32% diclofenac diethylamine, equivalent to 1%/2% diclofenac sodium). Human abdominal skin obtained during unrelated surgical procedures was stored at −20 °C until use. Skin specimens were thawed, prepared and placed in Franz diffusion cells (stratum corneum facing donor cell). The test formulation (~200 mg) was applied to the donor cell skin surface, and the receptor compartment was periodically sampled over 48 hours. The drug concentration in the receptor medium was determined by a validated HPLC method. Raman spectral imaging was performed to visualize the location and distribution of diclofenac.ResultsAfter 5 hours, the cumulative amount of hydrogel diclofenac transiting the skin was about 10 times that of the emulsion gel 1.16% (P=0.0004) and about twice that of the emulsion gel 2.32% (P=0.022). Similar results were seen after 9 hours. Raman spectroscopy showed that the hydrogel formulation was a homogeneous mixture of its various components, including diclofenac. The emulsion gels were non‐homogeneous, with diclofenac in close proximity to the lipophilic (paraffin) phase.ConclusionsThe transdermal transit of diclofenac from the hydrogel demonstrated a faster onset and a greater absorption rate than either emulsion gel formulation, suggesting that the hydrogel formulation may have a faster onset of action in underlying tissues vs. the emulsion gel products.
Highlights
Human abdominal skin samples from three patients were obtained via surgical skin removal procedures that were unrelated to the present investigation
The faster onset and increased transdermal absorption rate of hydrogel 1% compared with the emulsion gel formulations suggest that hydrogel 1% would have a faster onset of action in underlying tissues compared with the emulsion gel products
The results of this study indicate that hydrogel 1% was superior to emulsion gel 1% over 48 hours or emulsion gel 2%, over the first 9 hours, in its ability to effectively deliver diclofenac into and through human skin ex vivo
Summary
Musculoskeletal injuries and disorders (Bruyère et al, 2016; Smith, et al, 2016). Diclofenac (see Gan, 2010, for review) is the most com-. The challenge in topical transdermal drug delivery is to create a formulation that allows the drug to permeate quickly and efficiently through the stratum corneum, the outermost layer of skin that provides the barrier function of the organ (Haftek, et at., 1998). The primary pathway for absorption of topically applied drugs through the stratum corneum is thought to be this intercellular matrix (Vitorino, et al, 2015). Factors that influence the transdermal permeation of topically applied NSAID formulations include chemical structure and properties of the drug (e.g. molecular weight, hydrophilic vs hydrophobic properties, free‐acid or free‐base vs salt form of the molecule), and the composition of the formulation, the inclusion of excipients that enhance dermal penetration (Brunner et al, 2011; Escribano, et al, 2003; Folzer, et al, 2014; Lane, 2013; Marwah, et al, 2016; Nivsarkar, et al, 2015; Vitorino et al, 2015). Raman spectroscopy suggested differences in the location of diclofenac within the lipophilic and hydrophilic phases of each of the formulations that may contribute to the differences in transdermal drug transport
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
