Impact of Surfactant and Surfactant-Polymer Interaction on Desupersaturation of Clotrimazole

Zhang, Wei; Hate, Siddhi S.; Russell, David J.; Hou, Hao; Nagapudi, Karthik

doi:10.1016/j.xphs.2019.05.035

Cited by 18 publications

(12 citation statements)

References 44 publications

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“…Furthermore, the micelle formation of WSC can be related to the increased thermal equilibrium solubility of AM in WSC solution. A previous study reported that an increase in the equilibrium solubility of a drug by the presence of polymers decreases the apparent supersaturation level of the drug [ 29 ]. Therefore, AM concentration of 0.5 mg/mL was selected as a measure of the induction time to prevent the decrease in the apparent supersaturation level of AM.…”

Section: Resultsmentioning

confidence: 99%

The Impact of Water-Soluble Chitosan on the Inhibition of Crystal Nucleation of Alpha-Mangostin from Supersaturated Solutions

et al. 2022

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The use of an amorphous drugs system to generate supersaturated solutions is generally developed to improve the solubility and dissolution of poorly soluble drugs. This is because the drug in the supersaturation system has a high energy state with a tendency to precipitate. In the amorphous solid dispersion (ASD) formulation, it was discovered that polymer plays a critical role in inhibiting nucleation or crystal growth of the drugs. Therefore, this study aimed to evaluate the crystallization inhibition of water-soluble chitosan (WSC) on nucleation as well as crystal growth from alpha-mangostin (AM) and elucidate its inhibition mechanism in the supersaturated solutions. During the experiment, WSC was used as a polymer to evaluate its ability to inhibit AM nucleation. The interaction between WSC and AM was also estimated using FT-IR, NMR, and in silico study. The result showed that in the absence of polymer, the concentration of AM rapidly decreased due to the precipitation in one minute. Meanwhile, the addition of WSC effectively inhibited AM crystallization and maintained a supersaturated state for the long term. FT-IR measurement also revealed that the shift in the amine primer of WSC occurred because of the interaction between WSC and AM. In the 1H NMR spectra, the proton peaks of WSC showed an upfield shift with the presence of AM, indicating the intermolecular interactions between AM and WSC. Moreover, in silico study revealed the hydrogen bond interaction between the carbonyl group of AM with hydrocarbon groups of WSC. This indicated that WSC interacted with AM in the supersaturated solution and suppressed their molecular mobility, thereby inhibiting the formation of the crystal nucleus. Based on these results, it can be concluded that the interaction between drug polymers contributed to the maintenance of the drug supersaturation by inhibiting both nucleation and growth.

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Section: Resultsmentioning

confidence: 99%

The Impact of Water-Soluble Chitosan on the Inhibition of Crystal Nucleation of Alpha-Mangostin from Supersaturated Solutions

et al. 2022

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“…This partitioning can reduce the fraction of molecularly dissolved API, known as a true supersaturation, and therefore thermodynamically stabilize the drug solution (Feng et al, 2018). Furthermore, a more detailed systematic study on the effects of surfactants on API stabilization below and above of the CMC was conducted by Zhang et al (2019). The authors observed varied effects from surfactants on de-supersaturation, both promoting or reducing at surfactant concentrations below or above CMC, respectively.…”

Section: Effects Of Surfactants On Crystallization Inhibitionmentioning

confidence: 99%

Mechanisms of increased bioavailability through amorphous solid dispersions: a review

2019

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Amorphous solid dispersions (ASDs) can increase the oral bioavailability of poorly soluble drugs. However, their use in drug development is comparably rare due to a lack of basic understanding of mechanisms governing drug liberation and absorption in vivo. Furthermore, the lack of a unified nomenclature hampers the interpretation and classification of research data. In this review, we therefore summarize and conceptualize mechanisms covering the dissolution of ASDs, formation of supersaturated ASD solutions, factors responsible for solution stabilization, drug uptake from ASD solutions, and drug distribution within these complex systems as well as effects of excipients. Furthermore, we discuss the importance of these findings on the development of ASDs. This improved overall understanding of these mechanisms will facilitate a rational ASD formulation development and will serve as a basis for further mechanistic research on drug delivery by ASDs.

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“…In contrast, PVP K12 and PVP K25 maintained the initial supersaturation level of CLT for a long time; the CLT concentration in the PVP K12 solution started to decrease after 40 h, while the initial supersaturation level of CLT was maintained in the PVP K25 solution for 72 h. The rate of drug crystal nucleation in the supersaturated solutions is highly dependent on the supersaturation level of the drug . An increase in the equilibrium solubility of a drug in the presence of an additive decreases the apparent supersaturation level of the drug and delays the nucleation induction time of the drug . Thus, the effect of each additive on the crystalline solubility of CLT was investigated (Table ).…”

Section: Resultsmentioning

confidence: 98%

“…28 An increase in the equilibrium solubility of a drug in the presence of an additive decreases the apparent supersaturation level of the drug and delays the nucleation induction time of the drug. 46 Thus, the effect of each additive on the crystalline solubility of CLT was investigated (Table 1). NEP, PVP K12, and PVP K25 had little effect on the thermal equilibrium solubility of CLT, even at a concentration of 1000 μg/mL.…”

Section: ■ Resultsmentioning

confidence: 99%

NMR-Based Mechanistic Study of Crystal Nucleation Inhibition in a Supersaturated Drug Solution by Polyvinylpyrrolidone

Ueda

Yamamoto

Higashi

et al. 2022

Crystal Growth & Design

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In this study, the molecular states of supersaturated drugs and crystallization inhibitors in aqueous solutions were characterized using NMR to elucidate the inhibition mechanism of drug crystal nucleation in drug-supersaturated solutions. Polyvinylpyrrolidone (PVP) K12, PVP K25, and 1-ethyl-2-pyrrolidone (NEP) were used as additives to evaluate their ability to inhibit chlorthalidone (CLT) crystal nucleation. Although an inhibitory effect of NEP on the crystal nucleation of CLT was not observed, PVP effectively inhibited CLT crystallization and maintained CLT in a supersaturated state in the long term. In the 1D 1 H NMR spectra, the aromatic proton peaks of CLT showed an upfield shift with increasing CLT concentration, reflected by the self-association of CLT in aqueous solution; the number of self-associates increased with increasing supersaturation level. The presence of the additives in the aqueous solution induced downfield shifts of the CLT peaks, which were the largest in the PVP K25 solution and the smallest in the NEP solution. Nuclear Overhauser effect spectroscopy (NOESY) measurements revealed that the PVP formed a hydrophobic interaction with CLT via the carbon chain of PVP. Furthermore, the spin−spin relaxation rate of the supersaturated CLT was significantly increased by the addition of PVP K25, indicating the mobility suppression of supersaturated CLT by PVP K25, which can be caused by the intermolecular interactions between CLT and PVP K25. Furthermore, CLT mobility suppression by PVP K25 became more significant with increasing CLT supersaturation levels. This implies that PVP K25 interacted particularly with CLT self-associates formed in the supersaturated solution and suppressed their molecular mobility, thereby inhibiting the reorientation from the CLT self-associates to the crystal nucleus. The present study highlights the importance of the molecular weight of crystallization inhibitors on the ability of mobility suppression of a self-associated drug due to the nucleation inhibition effect.

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Impact of Surfactant and Surfactant-Polymer Interaction on Desupersaturation of Clotrimazole

Cited by 18 publications

References 44 publications

The Impact of Water-Soluble Chitosan on the Inhibition of Crystal Nucleation of Alpha-Mangostin from Supersaturated Solutions

The Impact of Water-Soluble Chitosan on the Inhibition of Crystal Nucleation of Alpha-Mangostin from Supersaturated Solutions

Mechanisms of increased bioavailability through amorphous solid dispersions: a review

NMR-Based Mechanistic Study of Crystal Nucleation Inhibition in a Supersaturated Drug Solution by Polyvinylpyrrolidone

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