Impact of Poloxamer on Crystal Nucleation and Growth of Amorphous Clotrimazole

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2023 Aug 26

PMID 37631378

Authors

Jie Zhang

Ziqing Yang

Liquan Luo

Kang Li

Taotao Zi

Junjie Ren

Lei Pan

Ziyue Wang

Zihao Wang

Minzhuo Liu

Zhihong Zeng

Affiliations

Soon will be listed here.

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 () 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.

Citing Articles

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

Wang L, Ding Z, Wang Z, Zhao Y, Wu H, Wei Q Pharmaceutics. 2024; 16(1).

PMID: 38258119 PMC: 10818454. DOI: 10.3390/pharmaceutics16010109.

References

Shi Q, Zhang C, Su Y, Zhang J, Zhou D, Cai T . Acceleration of Crystal Growth of Amorphous Griseofulvin by Low-Concentration Poly(ethylene oxide): Aspects of Crystallization Kinetics and Molecular Mobility. Mol Pharm. 2017; 14(7):2262-2272. DOI: 10.1021/acs.molpharmaceut.7b00097. View

Mosquera-Giraldo L, Trasi N, Taylor L . Impact of surfactants on the crystal growth of amorphous celecoxib. Int J Pharm. 2013; 461(1-2):251-7. DOI: 10.1016/j.ijpharm.2013.11.057. View

Qian F, Tao J, Desikan S, Hussain M, Smith R . Mechanistic investigation of Pluronic based nano-crystalline drug-polymer solid dispersions. Pharm Res. 2007; 24(8):1551-60. DOI: 10.1007/s11095-007-9275-7. View

Ghebremeskel A, Vemavarapu C, Lodaya M . Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API: selection of polymer-surfactant combinations using solubility parameters and testing the processability. Int J Pharm. 2006; 328(2):119-29. DOI: 10.1016/j.ijpharm.2006.08.010. View

Newman A, Zografi G . What We Need to Know about Solid-State Isothermal Crystallization of Organic Molecules from the Amorphous State below the Glass Transition Temperature. Mol Pharm. 2020; 17(6):1761-1777. DOI: 10.1021/acs.molpharmaceut.0c00181. View

Zhang J, Liu M, Xu M, Chen Z, Peng X, Yang Q . Discovery of a new polymorph of clotrimazole through melt crystallization: Understanding nucleation and growth kinetics. J Chem Phys. 2023; 158(3):034503. DOI: 10.1063/5.0130600. View

Weuts I, Kempen D, Decorte A, Verreck G, Peeters J, Brewster M . Physical stability of the amorphous state of loperamide and two fragment molecules in solid dispersions with the polymers PVP-K30 and PVP-VA64. Eur J Pharm Sci. 2005; 25(2-3):313-20. DOI: 10.1016/j.ejps.2005.03.012. View

Qi S, Craig D . Recent developments in micro- and nanofabrication techniques for the preparation of amorphous pharmaceutical dosage forms. Adv Drug Deliv Rev. 2016; 100:67-84. DOI: 10.1016/j.addr.2016.01.003. View

Correa-Soto C, Gao Y, Indulkar A, Zhang G, Taylor L . Role of surfactants in improving release from higher drug loading amorphous solid dispersions. Int J Pharm. 2022; 625:122120. DOI: 10.1016/j.ijpharm.2022.122120. View

10.

Karekar P, Vyas V, Shah M, Sancheti P, Pore Y . Physicochemical investigation of the solid dispersion systems of etoricoxib with poloxamer 188. Pharm Dev Technol. 2009; 14(4):373-9. DOI: 10.1080/10837450802683974. View

11.

Jermain S, Brough C, Williams 3rd R . Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery - An update. Int J Pharm. 2017; 535(1-2):379-392. DOI: 10.1016/j.ijpharm.2017.10.051. View

12.

Zhang J, Guo M, Luo M, Cai T . Advances in the development of amorphous solid dispersions: The role of polymeric carriers. Asian J Pharm Sci. 2023; 18(4):100834. PMC: 10450425. DOI: 10.1016/j.ajps.2023.100834. View

13.

Pandi P, Bulusu R, Kommineni N, Khan W, Singh M . Amorphous solid dispersions: An update for preparation, characterization, mechanism on bioavailability, stability, regulatory considerations and marketed products. Int J Pharm. 2020; 586:119560. PMC: 8691091. DOI: 10.1016/j.ijpharm.2020.119560. View

14.

Vasconcelos T, Prezotti F, Araujo F, Lopes C, Loureiro A, Marques S . Third-generation solid dispersion combining Soluplus and poloxamer 407 enhances the oral bioavailability of resveratrol. Int J Pharm. 2021; 595:120245. DOI: 10.1016/j.ijpharm.2021.120245. View

15.

Zhang W, Hate S, Russell D, Hou H, Nagapudi K . Impact of Surfactant and Surfactant-Polymer Interaction on Desupersaturation of Clotrimazole. J Pharm Sci. 2019; 108(10):3262-3271. DOI: 10.1016/j.xphs.2019.05.035. View

16.

Yao X, Benson E, Gui Y, Stelzer T, Zhang G, Yu L . Surfactants Accelerate Crystallization of Amorphous Nifedipine by Similar Enhancement of Nucleation and Growth Independent of Hydrophilic-Lipophilic Balance. Mol Pharm. 2022; 19(7):2343-2350. DOI: 10.1021/acs.molpharmaceut.2c00156. View

17.

Zhang J, Shi Q, Tao J, Peng Y, Cai T . Impact of Polymer Enrichment at the Crystal-Liquid Interface on Crystallization Kinetics of Amorphous Solid Dispersions. Mol Pharm. 2019; 16(3):1385-1396. DOI: 10.1021/acs.molpharmaceut.8b01331. View

18.

Schittny A, Philipp-Bauer S, Detampel P, Huwyler J, Puchkov M . Mechanistic insights into effect of surfactants on oral bioavailability of amorphous solid dispersions. J Control Release. 2020; 320:214-225. DOI: 10.1016/j.jconrel.2020.01.031. View

19.

Chen Y, Wang S, Wang S, Liu C, Su C, Hageman M . Sodium Lauryl Sulfate Competitively Interacts with HPMC-AS and Consequently Reduces Oral Bioavailability of Posaconazole/HPMC-AS Amorphous Solid Dispersion. Mol Pharm. 2016; 13(8):2787-95. DOI: 10.1021/acs.molpharmaceut.6b00391. View

20.

Zhang J, Liu Z, Wu H, Cai T . Effect of polymeric excipients on nucleation and crystal growth kinetics of amorphous fluconazole. Biomater Sci. 2021; 9(12):4308-4316. DOI: 10.1039/d1bm00104c. View