The interaction coefficient values indicated the effects of the variables in combination (see Table II). The authors had difficulty ranking the interaction effects, although the strongest interactions appeared to be between T and C. T–C interaction also suggest that S. aureus is more susceptible to cream formulations that contain a high concentration of Apifil than is C. albicans. More importantly, the various interactions appeared to be generally weak, suggesting that the variables were, to a large extent, acting independently of each other. This observation therefore implies that T is the most influential variable in this particular work because it had the largest effects.

Figure 2

The maximum amount (Q ₂₄ ) of BRB that permeated during the 24 h of the study was 6.20 ±0.23 mg/cm^-2 from Formulation P prepared without menthol. The flux was obtained by dividing the cumulative amount of drug permeated per cm² of the skin by time. The corresponding flux of BRB was 260.21 ±9.76 μg/cm^-2/hr^-1 for Formulation P.

Table III: Drug content, viscosity, amount of drug permeated in 24 h (Q24), % BRB released, flux (J), permeability coefficient (Kp), enhancement ratio (ER), and zero-order R2 values for the in vitro permeation study across rat epidermal membrane from cream formulations of BRB containing selected concentrations of menthol at the end of 24 h.

As the menthol concentration increased from 0 to 12.5% w/w, the permeability of BRB also increased, as indicated by an increase in both the permeability coefficient and enhancement ration (ER) (see Figure 2 and Table III). The authors observed a fivefold increase in the permeability of the drug from the cream containing 12.5% w/w of menthol (see Table III). Terpenes increase the drug's percutaneous permeation mainly by disrupting the intercellular packing of the subcutaneous lipids (18–20).