Summary
The study of the pharmacological problems of ophthalmology is a relatively neglected chapter in this specialty. The present paper is an attempt to summarize the results of recent research in the field of ophthalmo-pharmacology.
The therapeutic effect of many ophthalmic drugs depends partly or entirely upon their ability to permeate the coats of the eyeball. The conditions which determine a qualitative and quantitative passage of such drugs is the problem of the corneal permeability. Our knowledge of the problems of corneal permeability will improve with the application of the advances made in the allied sciences, especially in physical chemistry. In this actually confusing state of the problem, it seems to the writer that there are three outstanding experimental results. These results are the basis for further research which might bring a harmonious and complete understanding of the present problem, and thus improve the effectiveness of our pharmacological armamentarium.
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1.
The cornea exhibits an unidirectional permeability. Sodium chloride, oxygen, alkaloids, and acid dyes pass the cornea from without inward, while most of the basic dyes and carbon dioxide pass in the opposite direction (F. P. Fischer).
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2.
The corneal barrier might be considered a membrane containing a solvent permitting the passage of such substances as possess the appropriate solubilities. The corneal epithelium and probably the endothelium are barriers to substances which are purely water-soluble, while fat-soluble substances do not pass through the stroma. Substances which do get through the entire cornea have a characteristically biphasic solubility (Cogan et al.; Swan and White).
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3.
The molecular structure is a decisive factor in the penetration. The polar and non-polar structure of a compound determines its water and Lipoid solubility and thus the rate of penetration (Swan and White).
The ideal pH of collyria is supposed to be that of tears, namely close to 7–7.4. A considerable deviation of the pH value in ophthalmic solutions causes disturbances necessitating adjusting and buffering. The interest for the pratical application of buffers in collyria centered mainly around three buffer systems, that of Atkins and Pantin, Palitzsch's buffer and Søzirensen's phosphate buffer system. Each of these systems has advantages in buffering certain solutions and disadvantages in others. A thorough comparative study has not as yet been made.
The principle of buffering ophthalmic solutions is not uniformly applicable, since the physiological effectiveness of various substances is greater at different pH levels. The ideal collyrium has a pH at which the maximum comfort is associated with the maximum effectiveness. Since each of these maxima is achieved at a different pH level of the solution in use, a compromise approximating midway between the two pH values will often be necessary in order to achieve the maximum comfort with the maximum effectiveness.
Another character of a collyrium is its tonicity. Like the pH, the tonicity of the solution is also approximating adequacy if it is close to that of tears, and it was believed to be isosmotic with a 0.9 % sodium chloride solution. As most ophthalmic drugs are heterotonic at the required concentration in distilled water, their solutions require the addition of salts. To render a solution isotonic requires a complex calculation, which can be simplified by the use of Nicola's formula.
Most ophthalmic solutions in use are readily contaminated by bacteria, yeasts, molds, and fungi. Therefore the addition of a preservative to collyria is indicated. The most adequate preservative as yet known is a combination of two parahydroxybenzoic acid esters, which secures a satisfactory stability of ophthalmic preparations.
The penetration of many ophthalmic drugs can be enhanced by the use of surface active agents; so-called wetting agents or detergents. In many standard antiseptics the bactericidal activity is due in part to their wetting ability. Similarly, local anesthetics have wetting properties that favor the penetration of ophthalmic drugs. Research concerning the applicability of wetting agents in opthhalmic use is in an early stage, but the results are encouraging enough to justify further investigation.
The problem of the contact lens fluid involves similar considerations as collyria generally, namely that of the chemical composition the pH, and the tonicity. Disturbances will arise if there is an inadequacy in the lens fluid. As yet there is no adequate lens fluid, and hence the wearing time of contact lenses isUmited. A new field of research for better contact lens fluids was opened by Obrig and Schaeffer by the investigation of the applicabil ity of amino acids in the solution used as the fluid lens. These experiments are in their primary stage.
The absorption of the active ingredients from an ointment base depends on the chemical and physical characteristics of the base itself. The best utilization of drugs is obtained with a base in which fat is emulgated in water, and water forms the surface active phase, i. e. with an oil-water emulsion.
The average regenerative activity of the corneal tissue is inhibited by local anesthetics. To stimulate “normal” corneal generation through local application, the writer investigated a combination of amino acids for their efficacy in accelerating proliferation. He found that the proliferating cells may utilize these amino acids in the synthesis of new protoplasm, thus stimulating cell neoformation. The rate of regeneration is highly accelerated by the local application of amino acids.
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Schaeffer, A.J. Some aspects of ocular pharmacology. Doc Ophthalmol 4, 227–319 (1950). https://doi.org/10.1007/BF00141319
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DOI: https://doi.org/10.1007/BF00141319