Interplay of Adsorption, Supersaturation and the Presence of an Absorptive Sink on Drug Release from Mesoporous Silica-B
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RESEARCH PAPER
Interplay of Adsorption, Supersaturation and the Presence of an A b s o r p t i v e S i n k o n D r u g Re l e a s e f r o m M e s o p o r o u s Silica-Based Formulations Siddhi S. Hate 1 & Susan M. Reutzel-Edens 2 & Lynne S. Taylor 1
Received: 29 April 2020 / Accepted: 10 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
ABSTRACT Purpose Mesoporous silica-based formulations of poorly soluble drugs may exhibit incomplete drug release due to drug remaining adsorbed on the silica surface. The goal of this study was (1) to evaluate the adsorption tendency of atazanavir from aqueous solution onto mesoporous silica (SBA-15) and (2) to determine if the drug release from mesoporous silica formulations was promoted by the presence of an absorptive compartment during dissolution testing. Methods Atazanavir (ATZ) formulations with different drug loadings were prepared by incipient impregnation. The solidstate properties of the formulations were analyzed by X-ray diffraction (XRD), differential scanning calorimetry (DSC), infrared spectroscopy and thermogravimetric analysis. Drug release was compared for closed compartment versus absorptive dissolution testing at gastric and intestinal pH. Results XRD and DSC showed that all formulations were amorphous. Infrared spectra indicated intermolecular interactions between silanol groups in SBA-15 and carbonyl groups in atazanavir. Nanoconfinement of drug in silica mesopores was suggested by thermal analysis. Closed compartment dissolution testing showed incomplete drug release, largely due to the adsorption tendency of ATZ. However, coupled dissolution-absorption studies showed complete release over a 240 min time period. This suggested that the depletion of drug in the dissolution medium due to drug diffusion across the membrane promotes drug release. Drug release was further improved when the formulation was first added to fasted state gastric pH conditions followed by pH* Lynne S. Taylor [email protected] 1
Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA
2
Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana 46285, USA
shift to intestinal conditions, which was attributed to the higher solubility of atazanavir at low pH. However, ATZ mesoporous silica formulations showed a poorer overall absorption behavior relative to a polymer-based amorphous solid dispersion formulation. Conclusion This study highlights that absorptive dissolution conditions promote drug desorption from the silica surface and hence, enhance drug release. Further, the influence of solution pH on drug release underscores the need to consider how variations in physiological conditions may impact the performance of mesoporous silica-based formulations.
KEY WORDS adsorption isotherm . dissolution . membrane absorption . mesoporous silica-based formulations . nanoconfinement
ABBREVIATIONS ASD ATZ DL DSC FTIR GI HPLC HPMC LLPS MPS PXRD TGA
Amorphous Solid Dispersions Ataza
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