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Dissolution of bicalutamide single crystals in aqueous solution : significance of evolving topography in accelerating face-specific kinetics
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Maddar, Faduma, Adobes Vidal, Maria, Hughes, Leslie P., Wren, Stephen A. C. and Unwin, Patrick R. (2017) Dissolution of bicalutamide single crystals in aqueous solution : significance of evolving topography in accelerating face-specific kinetics. Crystal Growth & Design, 17 (10). pp. 5108-5116. doi:10.1021/acs.cgd.7b00401 ISSN 1528-7483.
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Official URL: http://dx.doi.org/10.1021/acs.cgd.7b00401
Abstract
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.
Item Type: | Journal Article | ||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||
Journal or Publication Title: | Crystal Growth & Design | ||||||||
Publisher: | American Chemical Society | ||||||||
ISSN: | 1528-7483 | ||||||||
Official Date: | 23 August 2017 | ||||||||
Dates: |
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Volume: | 17 | ||||||||
Number: | 10 | ||||||||
Page Range: | pp. 5108-5116 | ||||||||
DOI: | 10.1021/acs.cgd.7b00401 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access |
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