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The aim was to evaluate the skin permeation and accumulation profiles of a highly lipophilic fatty ester using the combination of various permeation enhancing techniques to study the potential of highly lipophilic fatty esters as local topical agents. Permeation and accumulation profiles of ketorolac stearate (C18:0) were studied using solubility improved formulation, supersaturated solution of permeant in enhancer vehicle, lipophilic receptor solution, enhancer pretreatment, and the removal of stratum corneum and delipidization of skins. Impermeability and minimal skin accumulation of ketorolac stearate could delineate a preliminary possibility for designing safer topical agents without systemic absorption.

Four crystal forms of ketorolac have been obtained by recrystallization in organic solvents under variable conditions. Different ketorolac polymorphs and pseudopolymorph were characterized by X-ray powder diffraction crystallography (XRD), Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). In the dissolution studies in water at 37 +/- 0.5 degrees C, four crystal forms showed different patterns. The solubility of Form I were the highest. The solubility decreased in rank order: Form I > Form II > Form III > Form IV. Form land Form III were shown to have a good physical stability at room temperature for 60 days. However, Form II is converted to Form III and Form IV is converted to Form I after 60 days storage. Therefore, these observations indicate that crystalline polymorphism for ketorolac is readily inter-convertible and the relationship may have to taken into consideration in the formulation of the drug.