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.
In vitro skin-permeation studies.
The authors investigated the penetration-enhancing effect of menthol on the permeability of cream formulations of BRB through
the excised rat epidermis. Permeation parameters for BRB in the cream formulations are shown in Table III. The cumulative
amount of drug permeation through the rat epidermis from cream formulations that contained various amounts of menthol is shown
in Figure 2.
The maximum amount (Q
) 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.
The authors observed a marked effect of menthol on BRB skin permeation. The cumulative amounts (Q
) of BRB that permeated over 24 h increased from 9.43 ±0.34 to 35.07 ±0.95 mg cm-2 for cream formulations containing 2.5 and 12.5 %w/w of menthol, respectively. The corresponding flux values ranged from
391.73 ±12.58 to 1485.75 ±42.93 μg cm-2 /h-1 . However, a lag period of 1 h was observed for both formulations. The drug-permeation data were consistent with zero-order
kinetics from 2 to 24 h with a lag period of about 1 h for all cream formulations (see Table III).
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).