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Dry powder inhalers (DPI) are important for topical drug delivery to the lungs, but characterising the pre-aerosolised powder microstructure is a key initial step in understanding the post-aerosolised blend performance. In this work, we characterise the pre-aerosolised 3D microstructure of an inhalation blend using correlative multi-scale X-ray Computed Tomography (XCT), identifying lactose and drug-rich phases at multiple length scales on the same sample. The drug-rich phase distribution across the sample is shown to be homogeneous on a bulk scale but heterogeneous on a particulate scale, with individual clusters containing different amounts of drug-rich phase, and different parts of a carrier particle coated with different amounts of drug-rich phase. Simple scalings of the drug-rich phase thickness with carrier particle size are used to derive the drug-proportion to carrier particle size relationship. This work opens new doors to micro-structural assessment of inhalation powders that could be invaluable for bioequivalence assessment of dry powder inhalers.
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http://dx.doi.org/10.1016/j.ejpb.2023.08.016 | DOI Listing |
Int J Pharm
December 2024
Department of Pharmacy and Biotechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.
Polyoxylglycerides-based solid mixtures, commercially known as Gelucire®, are excipients commonly used for bioavailability improvement of poorly water-soluble drugs. However, their effect on solutions containing hydrophobic drugs above crystalline solubility has not yet been explored. The goal of this study was to investigate the impact of a mix of two commercial Gelucire® with high HLB values (Gelucire®50/13 and Gelucire®48/16) on the amorphous solubility and crystallization from supersaturated solutions of ketoprofen, used as model drug.
View Article and Find Full Text PDFInt J Pharm
December 2024
CMAC, University of Strathclyde, Technology and Innovation Centre, 99 George Street, Glasgow, G1 1RD, UK; Strathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.
The impact of drug saturation and processing regime on the microstructure of amorphous solid dispersions (ASDs) produced by hot-melt extrusion (HME) has been investigated. By exploring various combinations of drug loadings and processing temperatures, a range of drug saturation points were obtained by HME. The process was monitored with an in-line low-frequency Raman probe to construct the respective solubility phase diagram (i.
View Article and Find Full Text PDFJ Pharm Sci
January 2025
Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, IN 47907, United States. Electronic address:
The mechanisms of drug release from amorphous solid dispersions (ASDs) are complex and not fully explored, making it difficult to optimize for in vivo performance. A recurring behavior has been the limit of congruency (LoC), a drug loading above which the ASD surface forms an amorphous drug-rich barrier in the presence of water, which hinders release, especially in non-sink conditions. Drug-polymer interactions and drug glass transition temperature were reported to affect the LoC.
View Article and Find Full Text PDFJ Pharm Sci
January 2025
Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, Indiana, USA. Electronic address:
Amorphous solid dispersions (ASDs) typically show improved dissolution and generate supersaturated solutions, enhancing the oral bioavailability of poorly soluble drugs. To gain insights into intraluminal ASD behavior, we utilized two poorly soluble drugs with different crystallization tendencies, atazanavir and posaconazole, prepared as ASDs at a 10% drug loading with hydroxypropyl methylcellulose acetyl succinate (HPMCAS). We evaluated their release in aspirated fasted-state human intestinal fluid (FaHIF), and multi-component fasted-state simulated intestinal fluid (composite-FaSSIF), characterizing the supersaturation profiles and drug-rich nanodroplets that formed.
View Article and Find Full Text PDFJ Pharm Sci
January 2025
Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, IN 47907, United States. Electronic address:
Hydroxypropyl methyl cellulose acetate succinate (HPMCAS) is one of the polymers of choice in formulating amorphous solid dispersions (ASDs) and helps to sustain high levels of drug supersaturation by delaying drug crystallization. Herein, the impact of HPMCAS chemistry on the solution crystallization kinetics of a fast-crystallizing lipophilic drug, posaconazole (PCZ), from the aqueous bulk phase and the drug-rich phase generated by liquid-liquid phase separation (LLPS), was studied. Three grades of HPMCAS: L, M, and H, which differ in the degree of acetyl and succinoyl substitution (A/S ratio), were compared.
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