Dissolution Behavior and Thermodynamic Stability of Fused-Sugar Dispersions of a Poorly Water-Soluble Drug

Abstract

The current research was undertaken to develop and evaluate dissolution profiles of thermodynamically stabilized sugar dispersions of the poorly water-soluble, model drug etoricoxib (ETX). Fused-sugar dispersions were formulated using sorbitol, xylitol, and maltose separately, and the binary systems were stabilized by incorporation of the antiplasticizing agents poloxamer 407 and PVP K30 to obtain ternary and quaternary systems. The sugar dispersions (F1-F12) were subjected to in vitro dissolution studies, and based on model-independent dissolution parameters, ETX-sorbitol binary/ ternary/composite systems were selected for thermodynamic stability study. The aged ETX-sorbitol composite dispersion (SF8) displayed the highest percent dissolution efficiency (%DE 80min of 78.48), the minimum t 50% of 4.45 min, and the least tendency to recrystallize (D cryst of 0.68), confirming maximum amorphization and thermodynamic stability among all the composite dispersions. The SEM photomicrographs reveal complete miscibility of drug in the aged quaternary dispersion SF8, and its diffuse reflectance (DR) spectrum confirms the absence of any chemical change. Conclusively, sorbitol binary systems can be effectively stabilized by incorporation of PVP K30-poloxamer 407 and retain the dissolution characteristics of sugar dispersions upon aging.

Sugars and Polyols of Natural Origin as Carriers for Solubility and Dissolution Enhancement

“…Particularly noteworthy is the finding that a 1:40 ratio of drug to xylitol formed a eutectic system that yielded the most substantial aqueous solubility enhancement (31.7%) [104]. Similar results were reported in several studies, where xylitolbased solid dispersions formed a two-phase solid crystalline suspension [76,[105][106][107].…”

“…These additives have been reported to effectively reduce the sugar component's recrystallisation during ageing, leading to improved thermodynamic stability. In addition to improved stability, the ternary systems display higher dissolution rates because of a synergistic effect [76,77].…”

“…In all cases, these dispersions enhance solubility and dissolution rates by improving the wettability of the drug particles. Studies have indicated that xylitol SDs show either a similar or superior solubility and dissolution behaviour compared with sorbitol [76] and mannitol [107], respectively. A key challenge highlighted in these studies is a lack of thermodynamic stability, attributable to crystal growth during storage and resulting in reduced dissolution rates [76,105,106].…”

Utilization and performance evaluation of mixed matrix membranes for the treatment of produced water: A review

“…The hydroxyl and carboxyl groups formed on the ends of inorganic fillers such as CNT and at defect sites concentrate on the ends of inorganic fillers such as CNT and at defect sites, making them more reactive and hence greater dispersion (Rizzuto et al, 2018). The presence of the same size charged particles on the surface of CNT enables the tubes to repel each other to keep the solution dispersed (Nasiri et al, 2017; Singh et al, 2011). Part 3 of this paper mentions that some researchers have used this method.…”

“…Their smooth graphitic layers create a frictionless path for ultrafast mass transportation, leading to a significant flux enhancement in CNT-based nanocomposite membranes. Including fillers modifies the morphology, which alters the transport phenomenon, and ultimately impacts the overall performance of the newly formed membranes; therefore, interfacial compatibility between the two phases is critical (Singh et al, 2011). However, single-wall and double-wall CNT are unfavorable due to their higher production cost.…”