(502d) Viscoelastic Properties and Dissolution Kinetics of Amorphous Drug Dispersion Films, Utilizing the Quartz Crystal Microbalance | AIChE

(502d) Viscoelastic Properties and Dissolution Kinetics of Amorphous Drug Dispersion Films, Utilizing the Quartz Crystal Microbalance


Isbell, M. A. - Presenter, Imperial College London
Heng, J. Y. Y., Imperial College London
Zhang, G. G. Z., AbbVie Inc.
Amorphous drug dispersions are becoming more and more utilized within the pharmaceutical industry, along with their academic study1-2. Their primary use is in facilitating the intake of poorly water soluble drugs by patients3-4. Plenty of research has been performed on understanding their physiochemical characteristics and stability in a wide range of conditions2, 5. Of the research published, little has gone into real time studies of the physiochemical properties of such films as they degrade. Our team, sought to utilize the Quartz Crystal Microbalance (QCM) to visualize how these drug blended films had altered physiochemical properties from unloaded ones in a variety of different environments6.

Carbamazepine and Copovidone were the compounds used to form amorphous drug films that were spun cast onto the QCM sensors. Solution blends in Methanol of 17% Copovidone weight by volume and Carbamazepine drug loadings of 35 to 5 mg/mL were used and spun cast. The lack of crystallinity was proven by a combination of several instrumental techniques including optical microscopy, Powder X-ray Diffraction (PXRD), and Differential Scanning Calorimetry (DSC), and the presence of Carbamazepine was shown via Fourier transform infrared spectroscopy (FTIR).

Quantitative data, including the thickness, density, and viscoelasticity, on the structural properties of the film was obtained by utilizing both the Sauerbrey and Viscoelastic models for the films. The films were found to be better modelled as soft rather than rigid, and the Sauerbrey model was not as effective. The data obtained from the Viscoelastic model was corroborated with ellipsometry to obtain a thickness. Within this body of work, the films at varying temperatures and on different surfaces to analyse their effects on the physiochemical properties of the films.

Furthermore, the dissolution kinetics of these films when submerged in water and ethanol were investigated in real time. In water, depending on the drug loading, this led to the nucleation and crystallization of the Carbamazepine in the excipient film, where the contact of the particles on the sensors are seen. The particle sizing was performed using Dynamic Light Scattering (DLS) to obtain size measurements of the Carbamazepine powder that formed.

All these works combined, showcase the strength of the QCM as a surface specific tool and its potential within the pharmaceutical formulations industry in helping to optimize the combinations of excipients and active pharmaceutical ingredients. Additionally, it offers strong insight into how the properties of the amorphous drug films change with temperature. Future studies could utilize alternative sensors and cells to further expand our knowledge and understanding of these amorphous drug films.


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