| Popis: |
Pilocarpine nitrate solutions, pH 4.0, containing equimolar (0.0667 M) concentrations of acetic acid/sodium acetate, mono-/ dibasic sodium phosphate and citric acid/sodium citrate buffers were employed examine the effect of buffer capacity and buffering agents on ocular drug absorption in rabbits. Two new buffer parameters, termed average buffer capacity and residual buffer capacity, were introduced to elucidate the importance of buffer functionality and ionization values on the in vivo time course of lacrimal fluid pH. Buffer effect on the precorneal disposition of pilocarpine and inulin were also quantitated. Buffered solutions caused more induced lacrimation than an unbuffered solution at equivalent pH. Acetate buffer was found to cause excessive lacrimation, and may be inherently irritating to the eye. The utility of assessing the time course of lacrimal fluid pH and drug concentration to predict relative pilocarpine absorption efficiency was demonstrated. Pilocarpine was found to be less ocularly available from a phosphate-buffered solution than from the apparently more strongly buffered acetate formulation. This was attributed to phosphate exerting a resistance to pH re-equilibration near the pKa of pilocarpine due to its high residual buffer capacity. However, phosphate may still be regarded as the buffer of choice for pilocarpine since it appears to cause less irritation to the eye. The procedures described in this report may be adapted for ophthalmic preformulation studies to screen buffer systems or other formulation excipients. |
