IT is widely accepted that the physiological activity of alkaloidal eye preparations results from the penetration through the cornea of the free base portion rather than of the ionic form of the alkaloid (Cogan and Kinsey, 1942;Cogan and Hirsch, 1944; Swan and White, 1942). Therefore, the smaller the pKb value of the alkaloid, the fewer free base particles will be available for drug action at the normal eye pH 7T4. This necessitates the use of larger doses to obtain the desired physiological response for many alkaloids. Moreover, the instability of alkaline aqueous solutions of the alkaloidal drugs limits their usefulness.Since alkaloidal eye-drops are extensively used in eye examinations and treatment and are so potent that the lowest possible concentrations are desirable, efficient methods of using them have been much discussed.Blok (1945) prepared eye-drops in alkaline buffer, pH 8-9, in order to use smaller quantities of alkaloids, which were scarce during the German occupation of Holland. He found that a 05 per cent. alkaline pilocarpine solution produced a response similar to that from the usual 2 per cent. pilocarpine solution. However, the alkaline solution of the alkaloid was much less stable than the acidic solution.Floyd, Kronfeld, and McDonald (1953) measured the miotic response of subjects who had 1 per cent. pilocarpine hydrochloride, pH 4 0-4 2, instilled into one eye and the same solution buffered at pH 6-6-7-4 into the other. They found that the rate of absorption of the drug at each pH was approximately the same, although the more alkaline solution produced a slightly increased response. Riegelman and Vaughan (1958), in an extensive discussion of the subject of ophthalmic solutions, compared the miotic response to 1 per cent. pilocarpine solutions buffered at pH 4-2 with that to those buffered at pH 6-6.They likewise found that pilocarpine in the less acid solution had slightly more miotic effect but that the difference was statistically insignificant.One might. assume that these results were due to the fact that there was not enough additional alkaloidal free base available for increased penetration of the cornea at the highest pH used in the experiments.

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