Impact of formulation differences on performance of topical gels

Summary: Abstract Body: Changes in the components and composition of a topical formulation may influence its performance by impacting the physicochemical and structural (Q3) properties of the product and the thermodynamic activity (TA) of the active pharmaceutical ingredient (API). The objectives of this research were to evaluate the impact of 1) quantitative (Q2) variations of solubility modifiers on API’s bioavailability (BA) in the skin and 2) Q2 changes in several excipients on sensorial properties of the topical gels. For the first aim, diclofenac sodium gels were made with varying amounts of either propylene glycol (PG) or polyethylene glycol (PEG) 400. In an in situ drying study, the contents of water, PG, and API remaining on the human skin were assayed (n=3). Fractional solubility (FS) or TA was calculated as the ratio of API concentration to its saturation solubility (SS) in the formulation. An in vitro permeation test (IVPT) was performed (3 skin donors, 6 replicates) with a dose of 300 mg/cm2. For the second objective, several gels were prepared with various amounts of PG and ethanol and their relevant Q3 properties were measured. The sensorial perceptions of selected gels were evaluated in a human subject sensory panel test. The SS of diclofenac increased with increasing level of the solubilizing agents (0-80%) in the binary solutions. The drying studies revealed that ±25% variations in PG/PEG 400, as opposed to ±10%, resulted in discriminated TA profiles and greater differences in permeation for diclofenac, compared to the reference gel. The assessment of Q3 and in vivo sensory properties of vehicle gels, suggests that overall, higher ethanol content in the gels resulted in increased drying rate and reduced slipperiness of these formulations. Moreover, assessing the relevant Q3 data such as zero sheer viscosity may be valuable to predict changes in human sensorial perception of the gels. Further research is underway to develop and generalize such methods for multiple excipients and topical dosage forms. Tannaz Ramezanli¹, Ying Jiang¹, Narasimha Murthy², Yousuf Mohammed³, Markham C. Luke¹, Priyanka Ghosh¹ 1. US Food and Drug Administration, Silver Spring, MD, United States. 2. Topical Products Testing, Batesville, MS, United States. 3. Frazer Institute, Brisbane, QLD, Australia. Translational Studies: Preclinical