Modeling dissolution profiles to predict drug solubility

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

Rosario

Congreso; Reunión Internacional de Ciencias Farmacéuticas; 2023

Drug formulation is a process that requires a deep understanding of the interactions between thecomponents and the conditions under which they will be administered. Among the critical factorsthat 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 aspecific drug, in addition to presenting the feasibility of predicting this value through modeling ofdissolution data obtained from a 2-hour assay. For this, a dissolution test was performed accordingto USP 43 using sulfamethoxazole in powder form (SXZ) of pharmaceutical degree as model drugand 0.1N HCl pH 1.2 as dissolution medium. The test was performed at four differenttemperatures (25, 32, 37 and 42 °C) taking samples at predetermined time intervals for 120minutes. On the other hand, a solubility assay was carried out at each of the indicatedtemperatures to determine the experimental value of SXZ solubility in HCl. The Lumped-Gonzomathematical model was used to determine the initial dissolution rate (IDR) and the maximumamount of drug dissolved at infinite time, which corresponds to the theoretical solubility of thedrug. The results showed an increase in the IDR with temperature, from 131.5 mg/min at 25 °C to321.4 at 42 °C. On the other hand, the errors associated with the estimation of the solubility of SXZthrough the application of mathematical modeling in the dissolution tests were calculated. Theirvalues remained within an acceptable range, oscillating between 2.4% and 6.0% for the differenttemperatures evaluated. These findings support the robustness of the Lumped-Gonzo model inpredicting drug solubility. Furthermore, through the analysis of the experimental data, it waspossible to derive a mathematical expression that establishes a direct relationship between drugsolubility and temperature. This relationship provides a quantitative understanding of howtemperature influences the dissolution capacity of the drug and, consequently, its bioavailabilityand therapeutic efficacy. It is important to note that the solubility of the drug increased twofoldwhen the temperature was raised from 25 to 42 °C (0.419 mg/ml - 0.826 mg/ml). This studyhighlights the importance of taking temperature into account when formulating drugs anddesigning pharmaceutical treatments. Temperature strongly influences the dissolution kinetics ofa drug, and in turn affects its solubility and, therefore, its bioavailability. The application of theLumped-Gonzo model to predict solubility as a function of temperature proves to be a valuabletool in the optimization of pharmaceutical formulations. Ultimately, the quantitative relationshipbetween solubility and temperature highlights a crucial, but often underestimated aspect in drugformulation. This enables a more precise and directed approach towards the improvement ofpharmaceutical treatments.