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Figure 9.35 Aqueous humour levels of pilocarpine after dosing with 1002 mol dm03 ointment and solution in intact and abraded eyes. •, 25 mg of ointment, intact eyes; O, 25 mg of ointment, abraded eyes; ■, 25 mm3 of solution, intact eyes; □, 25 mm3 of solution, abraded eyes; all points represent an average of 8-16 eyes.

Reproduced from reference 16.

they can enter by both pathways. Penicillins, however, reach only low aqueous/plasma concentration ratios because they are removed from aqueous humour by absorption through the ciliary epithelium. Proteins are excluded, so that protein binding of ophthalmic drugs limits their absorption.

9.6.3 Influence of formulation

Pilocarpine activity has been compared in various formulations. Figure 9.35 shows some of the results on formulations, including results on ointments designed to prolong the contact of the drug with the cornea. One of the most difficult problems is to design vehicles which will retard drainage and prolong contact. Viscous polymer vehicles help to some extent but are not the complete answer. The rate of drainage of drops decreased as their viscosity increased and these factors contribute to an increased concentration of the drug in the precorneal film and aqueous humour.17 The magnitude of the concentration increase was small considering the 100-fold change in the viscosity, and it was concluded that the viscosity of the solution is not as important a factor in bioavailability as was previously thought.

The results of incorporating pilocarpine (V) (a relatively water-soluble drug) and fluoro-metholone (a lipophilic drug) into a water-in-oil ointment base can be compared in Fig. 9.36. Pilocarpine is thought to be released only when in contact with aqueous tear fluid, whereas the steroid, being soluble in the base, can diffuse through the base to replenish the surface concentrations and thus produce a sustained effect.

Structure V Pilocarpine (pKa = 7.05)
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