scholarly journals Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha-Cyclodextrin with Model Membranes by 1H-, 2H-, 31P-NMR and Electron Spin Resonance

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Jean-Claude Debouzy ◽  
David Crouzier ◽  
Fréderic Bourbon ◽  
Malika Lahiani-Skiba ◽  
Mohamed Skiba
Keyword(s):  
Solid Dispersion ◽  
Cyclosporine A ◽  
Amorphous Solid ◽  
Solid Matrix ◽  
Amorphous Solid Dispersion ◽  
Head Group ◽  
Polar Head Group ◽  
H Nmr ◽  
Higher Temperature ◽  
Global Increase

The properties of an amorphous solid dispersion of cyclosporine A (ASD) prepared with the copolymer alpha cyclodextrin (POLYA) and cyclosporine A (CYSP) were investigated by 1H-NMR in solution and its membrane interactions were studied by 1H-NMR in small unilamellar vesicles and by 31P 2H NMR in phospholipidic dispersions of DMPC (dimyristoylphosphatidylcholine) in comparison with those of POLYA and CYSP alone. 1H-NMR chemical shift variations showed that CYSP really interacts with POLYA, with possible adduct formation, dispersion in the solid matrix of the POLYA, and also complex formation. A coarse approach to the latter mechanism was tested using the continuous variations method, indicating an apparent 1 : 1 stoichiometry. Calculations gave an apparent association constant of log Ka = 4.5. A study of the interactions with phospholipidic dispersions of DMPC showed that only limited interactions occurred at the polar head group level (31P). Conversely, by comparison with the expected chain rigidification induced by CYSP, POLYA induced an increase in the fluidity of the layer while ASD formation led to these effects almost being overcome at 298 K. At higher temperature, while the effect of CYSP seems to vanish, a resulting global increase in chain fluidity was found in the presence of ASD.

In vitro and in vivo characterization on amorphous solid dispersion of cyclosporine A for inhalation therapy

2009 ◽  
Vol 138 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Satomi Onoue ◽  
Hideyuki Sato ◽  
Yohei Kawabata ◽  
Takahiro Mizumoto ◽  
Naofumi Hashimoto ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Cyclosporine A ◽  
Amorphous Solid ◽  
Inhalation Therapy ◽  
Amorphous Solid Dispersion ◽  
In Vivo Characterization

Improved dissolution and pharmacokinetic behavior of cyclosporine A using high-energy amorphous solid dispersion approach

2010 ◽  
Vol 399 (1-2) ◽  
pp. 94-101 ◽  
Author(s):  
Satomi Onoue ◽  
Hideyuki Sato ◽  
Kumiko Ogawa ◽  
Yohei Kawabata ◽  
Takahiro Mizumoto ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Cyclosporine A ◽  
Amorphous Solid ◽  
High Energy ◽  
Amorphous Solid Dispersion ◽  
Pharmacokinetic Behavior

Amorphous solid dispersion of cyclosporine A prepared with fine droplet drying process: Physicochemical and pharmacokinetic characterization

2017 ◽  
Vol 519 (1-2) ◽  
pp. 213-219 ◽  
Author(s):  
Hiroki Suzuki ◽  
Tatsuru Moritani ◽  
Tadahiko Morinaga ◽  
Yoshiki Seto ◽  
Hideyuki Sato ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Cyclosporine A ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Drying Process ◽  
Fine Droplet ◽  
Droplet Drying

scholarly journals Thermal stability of amorphous sugar matrix, dried from methanol, as an amorphous solid dispersion carrier

2018 ◽  
Author(s):  
Koreyoshi Imamura ◽  
K. Takeda ◽  
K. Yamamoto ◽  
H. Imanaka ◽  
N. Ishida
Keyword(s):  
Thermal Stability ◽  
Solid Dispersion ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Solid Matrix ◽  
Amorphous Solid Dispersion ◽  
Solid Mixture ◽  
Soluble Solid ◽  
Dispersion Technique ◽  
Thermal Stability Of

Developing a technique to disperse hydrophobic ingredients homogeneously in a water-soluble solid matrix (solid dispersion) is one of the topics that have been extensively investigated in the pharmaceutical and food industries. Recently, we have devised a novel solid dispersion technique (surfactant-free solid dispersion), in which a preliminarily amorphized sugar was dissolved in an organic media containing hydrophobic component, without using any surface active substances, and then vacuum dried into the amorphous solid mixture [Food Chem., 197 (2016) 1136; Mol. Pharm., 14 (2017) 791]. In this study, the physicochemical properties, especially thermal stability of the surfactant-free amorphous solid dispersion, were investigated. keywords: solid dispersion; amorphous sugar; surfactant-free; vacuum drying; glass transition temperature

Impact of Drug-Polymer Interaction in Amorphous Solid Dispersion Aiming for the Supersaturation of Poorly Soluble Drug in Biorelevant Medium

2020 ◽  
Vol 21 (5) ◽  
Author(s):  
Cassiana Mendes ◽  
Rafael G. Andrzejewski ◽  
Juliana M. O. Pinto ◽  
Leice M. R. de Novais ◽  
Andersson Barison ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Poorly Soluble ◽  
Poorly Soluble Drug ◽  
Drug Polymer Interaction ◽  
Biorelevant Medium ◽  
Polymer Interaction

scholarly journals Amorphous Solid Dispersion Tablets Overcome Acalabrutinib pH Effect in Dogs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 557
Author(s):  
Deanna M. Mudie ◽  
Aaron M. Stewart ◽  
Jesus A. Rosales ◽  
Nishant Biswas ◽  
Molly S. Adam ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Drug Exposure ◽  
Ph Effect ◽  
Hydroxypropyl Methylcellulose ◽  
Amorphous Solid ◽  
Gastric Ph ◽  
Patient Treatment ◽  
Oral Exposure ◽  
Amorphous Solid Dispersion ◽  
Plasma Drug

Calquence® (crystalline acalabrutinib), a commercially marketed tyrosine kinase inhibitor (TKI), exhibits significantly reduced oral exposure when taken with acid-reducing agents (ARAs) due to the low solubility of the weakly basic drug at elevated gastric pH. These drug–drug interactions (DDIs) negatively impact patient treatment and quality of life due to the strict dosing regimens required. In this study, reduced plasma drug exposure at high gastric pH was overcome using a spray-dried amorphous solid dispersion (ASD) comprising 50% acalabrutinib and 50% hydroxypropyl methylcellulose acetate succinate (HPMCAS, H grade) formulated as an immediate-release (IR) tablet. ASD tablets achieved similar area under the plasma drug concentration–time curve (AUC) at low and high gastric pH and outperformed Calquence capsules 2.4-fold at high gastric pH in beagle dogs. In vitro multicompartment dissolution testing conducted a priori to the in vivo study successfully predicted the improved formulation performance. In addition, ASD tablets were 60% smaller than Calquence capsules and demonstrated good laboratory-scale manufacturability, physical stability, and chemical stability. ASD dosage forms are attractive for improving patient compliance and the efficacy of acalabrutinib and other weakly basic drugs that have pH-dependent absorption.

scholarly journals Drug-Rich Phases Induced by Amorphous Solid Dispersion: Arbitrary or Intentional Goal in Oral Drug Delivery?

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 889
Author(s):  
Kaijie Qian ◽  
Lorenzo Stella ◽  
David S. Jones ◽  
Gavin P. Andrews ◽  
Huachuan Du ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Oral Drug Delivery ◽  
Drug Product ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Nucleation Theory ◽  
Product Development Process ◽  
Classical Nucleation Theory ◽  
Oral Drug ◽  
Amorphous Solid Dispersion

Among many methods to mitigate the solubility limitations of drug compounds, amorphous solid dispersion (ASD) is considered to be one of the most promising strategies to enhance the dissolution and bioavailability of poorly water-soluble drugs. The enhancement of ASD in the oral absorption of drugs has been mainly attributed to the high apparent drug solubility during the dissolution. In the last decade, with the implementations of new knowledge and advanced analytical techniques, a drug-rich transient metastable phase was frequently highlighted within the supersaturation stage of the ASD dissolution. The extended drug absorption and bioavailability enhancement may be attributed to the metastability of such drug-rich phases. In this paper, we have reviewed (i) the possible theory behind the formation and stabilization of such metastable drug-rich phases, with a focus on non-classical nucleation; (ii) the additional benefits of the ASD-induced drug-rich phases for bioavailability enhancements. It is envisaged that a greater understanding of the non-classical nucleation theory and its application on the ASD design might accelerate the drug product development process in the future.

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