Modeling dissolution profiles to predict drug solubility

CINTIA A. BRIONES; CAMPOS, SANTIAGO N.; CID, ALICIA G.; ROMERO ANALIA I.; VILLEGAS MERCEDES; GONZO ELIO E.; BERMUDEZ JOSÉ M.

Santa Fe

Congreso; 7ma Reunión Internacional de Ciencias Farmacéuticas. RICiFa; 2023

Drug formulation is a process that requires a deep understanding of the interactions between the components and the conditions under which they will be administered. Among the critical factors that influence the efficacy and action of drugs, temperature is of great importance. In this context, the main objective of this work was to evaluate the impact of temperature on the solubility of a specific drug, in addition to presenting the feasibility of predicting this value through modeling of dissolution data obtained from a 2-hour assay. For this, a dissolution test was performed according to USP 43 using sulfamethoxazole in powder form (SXZ) of pharmaceutical degree as model drug and 0.1N HCl pH 1.2 as dissolution medium. The test was performed at four different temperatures (25, 32, 37 and 42 °C) taking samples at predetermined time intervals for 120 minutes. On the other hand, a solubility assay was carried out at each of the indicated temperatures to determine the experimental value of SXZ solubility in HCl. The Lumped-Gonzo mathematical model was used to determine the initial dissolution rate (IDR) and the maximum amount of drug dissolved at infinite time, which corresponds to the theoretical solubility of the drug. The results showed an increase in the IDR with temperature, from 131.5 mg/min at 25 °C to 321.4 at 42 °C. On the other hand, the errors associated with the estimation of the solubility of SXZ through the application of mathematical modeling in the dissolution tests were calculated. Their values remained within an acceptable range, oscillating between 2.4% and 6.0% for the different temperatures evaluated. These findings support the robustness of the Lumped-Gonzo model in predicting drug solubility. Furthermore, through the analysis of the experimental data, it was possible to derive a mathematical expression that establishes a direct relationship between drug solubility and temperature. This relationship provides a quantitative understanding of how temperature influences the dissolution capacity of the drug and, consequently, its bioavailability and therapeutic efficacy. It is important to note that the solubility of the drug increased twofold when the temperature was raised from 25 to 42 °C (0.419 mg/ml - 0.826 mg/ml). This study highlights the importance of taking temperature into account when formulating drugs and designing pharmaceutical treatments. Temperature strongly influences the dissolution kinetics of a drug, and in turn affects its solubility and, therefore, its bioavailability. The application of the Lumped-Gonzo model to predict solubility as a function of temperature proves to be a valuable tool in the optimization of pharmaceutical formulations. Ultimately, the quantitative relationship between solubility and temperature highlights a crucial, but often underestimated aspect in drug formulation. This enables a more precise and directed approach towards the improvement of pharmaceutical treatments.