Assessment of the Effect of Camphor on in-vitro Permeation of Granisetron HCl Gels by Microdialysis and Conventional Sampling Technique

The primary objective of this study was to assess the effect of Camphor as a penetration enhancer on the in-vitro permeability of Granisetron HC1 KlucelRTM gels using Modified Franz Diffusion cells with cellulose and excised porcine ear skin as membrane. The secondary objective was to assess the possibility to use microdialysis to sample the receiver compartment and to compare permeability data with those obtained by conventional fluid withdrawal.;Granisetron HC1 (2%) gels were prepared by dissolving 400 mg of Granisetron HC1 in Ethanol-Water (60:40 v/v %) and adding 2% KlucelRTM as a gelling agent. The effect of Camphor was tested at different concentrations: 0%, 1.5%, 2.5%, and 3.5%. Camphor is a monoterpene penetration enhancer that has also antipruritic, analgesic, and anesthetic effect at concentrations in the range 3 to 11%. However, it may also exhibit severe systemic side effects. The Modified Franz Diffusion cells consisted of an 8 ml receiver compartment, a 1.0 cm2 exchange membrane (cellulose or porcine skin) and a donor compartment where 1.0 g of gel was placed. The receiver compartment was filled with ringer-lactate solution. A custom made linear microdialysis probe with one cm dialysis membrane was arranged through the side arms of the modified Franz Diffusion cell. The probe was connected to a precision pump with TeflonRTM tubing and perfused with a ringer-lactate solution at a rate of 111l/min. Microdialysis samples were collected every 30 minutes for 7 hours. Conventional samples were collected by withdrawing 504 from the receiving compartment at the midpoint of the microdialysis sampling interval and by replacing the same volume with fresh ringer solution. The samples were then analyzed by a validated HPLC method. Microdialysis probe recovery was previously determined at 400, 300, 200, 100, 50 and 251.1g/ml. All experiments were performed at least in triplicate. Microdialysis recovery was independent of concentration in the range tested. Average recovery was 0.73+1-0.05 (n=3). Dialysates collected during the permeability studies were corrected by the recovery factor and plot versus the mid-point of the time collection interval.;The results showed that permeability of Granisetron.HCL across porcine skin increased with Camphor strenght, whereas Camphor did not affect the release from the gels in the cellulos-membrane studies. This trend was observed with both microdialysis and conventional sampling. However, a paired t-test showed a statistically significant difference between the permeability parameters (Flux, T lag and Cumulative amount) calculated from each sampling method (microdialysis versus conventional) in the cellulose membrane experiments. On the contrary, the flux calculated from excised porcine skin experiments were not statistically significantly different, whereas the T-lag and Cumulative amount were significantly different also for the porcine skin experiment. In conclusion, the two sampling methods may provide different absolute parameter values; however, the relative trends are consistent.