Impact of Poloxamer on Crystal Nucleation and Growth of Amorphous Clotrimazole

Abstract

Surfactants have been widely used as effective additives to increase the solubility and dissolution rates of amorphous solid dispersions (ASDs). However, they may also generate adverse effects on the physical stability of ASDs. In this study, we systematically investigated the impacts of poloxamer, a frequently used surfactant, on the crystallization of amorphous clotrimazole (CMZ). The added poloxamer significantly decreased the glass transition temperature (Tg) of CMZ and accelerated the growth of Form 1 and Form 2 crystals. It was found that the poloxamer had an accelerating effect on Form 1 and Form 2 but showed a larger accelerating effect on Form 1, which resulted from a combined effect of increased mobility and local phase separation at the crystal–liquid interface. Additionally, the added poloxamer exhibited different effects on nucleation of the CMZ polymorphs, which was more complicated than crystal growth. The nucleation rate of Form 1 was significantly increased by the added poloxamer, and the effect increased with increasing P407 content. However, for Form 2, nucleation was slightly decreased or unchanged. The nucleation of Form 2 may have been influenced by the Form 1 crystallization, and Form 2 converted to Form 1 during nucleation. This study increases our understanding of poloxamer and its impacts on the melt crystallization of drugs.

The Development of an Oral Solution Containing Nirmatrelvir and Ritonavir and Assessment of Its Pharmacokinetics and Stability

“…The addition of the surfactants HCO and Tween facilitated micellization of the system, resulting in enhanced recrystallization inhibition in the supersaturated solution of RTV [ 42 ]. The impact of surfactants on drug crystallization in saturated solutions is multifaceted, including the crystalline nucleation induction time and desaturation rates [ 43 ].…”

“…system, resulting in enhanced recrystallization inhibition in the supersaturated solution of RTV [42]. The impact of surfactants on drug crystallization in saturated solutions is multifaceted, including the crystalline nucleation induction time and desaturation rates [43]. The results of the evaluation of particle size, depicted in Figure 2C,D, demonstrate that the particles in the medium with HCO were smaller and more uniformly dispersed than those in the other surfactant solutions.…”