Effect of change in vehicle composition on ophthalmic bioavailability of benzylpenicillin

The stability and bioavailability of benzylpenicillin ophthalmic solutions were determined at pH 5, 6, 6.5, 7 and 8 in citrate buffer. The stability of benzylpenicillin solutions stored at room temperature was greatest at pH 6.6-7 while at 2-4 degrees C stability was greatest at pH 6.5. The uptake by corneal and aqueous humour of benzyl [14-C] penicillin into ovine eyes was greatest at a pH of 6.5, which indicates that for optimum stability and bioavailability benzylpenicillin ophthalmic solutions should be prepared in citrate buffer at pH 6.5. Under these conditions the stability of the refrigerated preparation is acceptable for a normal treatment period.