Enhancement of Amorphous Celecoxib Stability by Mixing It with Octaacetylmaltose: The Molecular Dynamics Study

Abstract

In this paper, we present a novel way of stabilization of amorphous celecoxib (CEL) against recrystallization by preparing binary amorphous celecoxib-octaacetylmaltose (CEL-acMAL) systems by quench-cooling of the molten phase. As far as we know this is the first application of carbohydrate derivatives with acetate groups to enhance the stability of an amorphous drug. We found that CEL in the amorphous mixture with acMAL is characterized by a much better solubility than pure CEL. We report very promising results of the long-term measurements of stability of the CEL-acMAL binary amorphous system with small amount of stabilizer during its storage at room temperature. Moreover, we examined the effect of adding acMAL on molecular dynamics of CEL in the wide temperature range in both the supercooled liquid and glassy states. We found that the molecular mobility of the mixture of CEL with 10 wt % acMAL in the glassy state is much more limited than that in the case of pure CEL, which correlates with the better stability of the amorphous binary system. By dielectric measurements and theoretical calculations within the framework of density functional theory (DFT), we studied the role of acMAL in enhancing the stability of amorphous CEL in mixtures and postulated which interactions between CEL and acMAL molecules can be responsible for preventing devitrification.

Agglomerated novel spray-dried lactose-leucine tailored as a carrier to enhance the aerosolization performance of salbutamol sulfate from DPI formulations

“…Neither a recrystallization nor a melting peak was observed in the 5 and 10% L -leucine carrier, which serves as an indicator of their higher stability against recrystallization. Such results follow similar patterns that have been presented elsewhere [31][32][33][34] where amorphous drug carriers were formulated in such a way as to increase amorphous stability. To make sure spray-dried lactose was in the amorphous state, a more reliable technique (PXRD) was used.…”

Molecular Dynamics and Physical Stability of Amorphous Nimesulide Drug and Its Binary Drug–Polymer Systems

“…Similar behavior was previously observed in the case of ezetimibe, celecoxib and sildenafil. 20,21,22,23 Figure 1 presents dielectric spectra collected at temperatures below T g . In this temperature region the structural relaxation becomes too slow to be observed and only secondary relaxation processes may be visible.…”

Thermodynamically controlled crystallization of glucose pentaacetates from amorphous phase

“…1 Recently, these compounds are gaining attention in pharmaceutical sciences, due to their ability to stabilize amorphous state of drug. 2 Drugs in the amorphous state have better bioavailability and solubility, therefore there is a need for additives that can prevent active ingredient (API) from crystallization. 3 Sugar peracetates are van der Waals compounds i.e.…”

“…5 Inhibitory crystallization effect of acetyl derivatives of carbohydrates was also found in mixtures with the celecoxib drug. 6 Crystallization is a two stage process. The first stage is related to the nucleation and the second one to the crystal growth.…”