The dissolution test of sodium salicylate from semi-solid formulation

Abstract

Introduction. The pharmaceutical dissolution test plays a key role in drug development and is used during the formulation stage for quality control testing and is an essential tool for estimating bioavailability. For the active pharmaceutical ingredient (API) that has an increased solubility, it is expected not to raise bioavailability issues, especially if the pharmaceutical form allows the active substance to dissolve rapidly within the expected physiological pH range after administration of the product. Dissolution test is listed in several Pharmacopeia: European, British, US and others, as a quality procedure both for solid and semisolid formulation like suppositories. Aim of study. This study aimed at the formulation by an optimised technology of suppositories with sodium salicylate and determination of its availability using in vitro dissolution testing. Methods and materials. Suppositories were prepared in series by two methods: hand rolling with the use of cocoa butter and by casting method with semisynthetic glycerides, both with addition of 2% polymer gel of sodium alginate. For the dissolution rate study, the Erweka dissolution tester, in the medium of purified water, by paddle method was used. The dosing was performed photocolorimetrically at 525 nm wavelength, based on the colour reaction with iron chloride. All reagents were chemically pure. Results. Sodium salicylate is an analgesic and antipyretic drug from the group of salicylic acid derivatives. It is prescribed for acute rheumatism, exudative pleurisy, non-rheumatic arthritis, gout, neuralgia, myalgia, etc., moreover it is also studied biopharmaceutical as a hydrotropic agent. Many medical protocols indicate long-term use of salicylates for children in single doses from 0.1 to 0.5 and for adults from 0.5 to 1.0. In order to avoid the mostly local side effects on the stomach, it is practised to prescribe them rectally. Suppositories are semi-solid pharmaceutical forms, which contain unit doses of one or more active substances which at room temperature are solid and melt at body temperature. For the study, according to the prescribed dose, suppositories with average mass of 2.0 gr were formulated on cocoa butter and semisynthetic glycerides with and without dispersion of sodium salicylate in 2% gel of sodium alginate. The results of sampling at 10, 20, 30, 45 and 60 minutes, showed a good release and dissolution of the sodium salicylate from cocoa butter suppositories (57%). The addition and dispersion of API in the natural polymer, based on polysaccharides, sodium alginate gel of 2%, increased the dissolving rate of sodium salicylate to 61%. For the semisynthetic glycerides the dispersion method did not statistically influence the dissolution % of the API. Conclusion. As a result of the study, suppositories were prepared on lipophilic excipients with cocoa butter and semi-synthetic glycerides with and without addition of polymer. The in vitro dissolution study showed that in determining the quality profile and bioavailability prediction of the semi-solid product - suppositories containing sodium salicylate - it will depend on the nature of the excipients and adjuvants used in formulation.