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Dissolution of Bicalutamide Single Crystals in Aqueous Solution: Significance of Evolving Topography in Accelerating Face-Specific Kinetics
Crystal Growth & Design ( IF 3.8 ) Pub Date : 2017-09-01 00:00:00 , DOI: 10.1021/acs.cgd.7b00401
Faduma M. Maddar 1 , Maria Adobes-Vidal 1 , Leslie P. Hughes 2 , Stephen A. C. Wren 2 , Patrick R. Unwin 1
Affiliation  

The dissolution kinetics of individual microscale bicalutamide (BIC) form-I crystals are tracked over time using in situ atomic force microscopy (AFM), with the evolution of crystal morphology used to obtain quantitative data on dissolution kinetics via finite element method (FEM) modeling of the dissolution reaction-diffusion problem. Dissolution is found to involve pit formation and roughening on all dissolving surfaces of the BIC crystal, and this has a strong influence on the overall dissolution process and kinetics. While all of the exposed faces (100), {051}, and {1̅02} show dissolution kinetics that are largely surface-kinetic controlled, each face has an intrinsic dissolution characteristic that depends on the degree of hydrogen bonding with aqueous solution, with hydrogen bonding promoting faster dissolution. Moreover, as dissolution proceeds with pitting and roughening, the rate accelerates considerably, so that there is an increasing diffusion contribution. Such insight is important in understanding the oral administration of poorly soluble active pharmaceutical ingredients (APIs) in crystal form. Evidently, surface roughening and defects greatly enhance dissolution kinetics, but the evolving crystal topography during dissolution leads to complex time-dependent kinetics that are important for modeling and understanding API release rates.

中文翻译:

比卡鲁胺单晶在水溶液中的溶解:不断变化的形貌在加速特定于表面的动力学中的意义

使用原位原子力显微镜(AFM)随时间跟踪单个微尺度比卡鲁胺(BIC)I型晶体的溶解动力学,利用晶体形态的演变通过有限元方法(FEM)建模获得溶解动力学的定量数据反应扩散的问题。发现溶解涉及BIC晶体所有溶解表面上的凹坑形成和粗糙化,这对整个溶解过程和动力学有很大影响。虽然所有暴露的面(100),{051}和{1̅02}都显示出很大程度上受表面动力学控制的溶解动力学,但每个面都有一个固有的溶解特性,这取决于氢与水溶液,氢的键合程度结合促进更快的溶解。而且,随着溶蚀随着点蚀和粗糙化的进行,速度大大加快,因此扩散贡献增加。这样的见解对于理解晶体形式的难溶性活性药物成分(API)的口服给药很重要。显然,表面粗糙和缺陷会大大增强溶解动力学,但是在溶解过程中不断发展的晶体形貌会导致复杂的时间依赖性动力学,这对于建模和了解API释放速率非常重要。
更新日期:2017-09-04
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