In this study, the influence of copolymer composition on drug-polymer solubility was investigated. The solubility of the model drug celecoxib (CCX) in various polyvinylpyrrolidone/vinyl acetate (PVP/VA) copolymer compositions (70/30, 60/40, 50/50 and 30/70 w/w) and the pure homopolymers polyvinylpyrrolidone (PVP) and polyvinyl acetate (PVA) was predicted at 25 °C using a thermal analysis method based on the recrystallization of a supersaturated amorphous dispersion (recrystallization method). These solubilities were compared with a prediction based on the solubility of CCX in the liquid monomeric precursors of PVP/VA, N-vinylpyrrolidone (NVP) and vinyl acetate (VA), using the Flory-Huggins lattice theory (liquid monomer solubility approach). The solubilities predicted from the liquid monomer solubility approach increased linearly with increasing VP/VA ratio from 0.03-0.60 w/w. Even though the solubilities predicted from the recrystallization method also increased with increasing VP/VA ratio from 0.02-0.40 w/w, the predicted solubility seemed to approach a plateau at high VP/VA ratios. Increasing positive deviations from the Gordon-Taylor equation with increasing VP/VA ratio indicated strong interactions between CCX and the VP repeat unit, which was in accordance with the relatively high solubilities predicted using both methods. As the solubility plateau may be a consequence of steric hindrance caused by the size differences between CCX and the VP repeat units, it is likely that a CCX molecule interacting with a VP repeat unit hinders another CCX molecule from binding to the neighboring repeat units in the polymer chain. Therefore, it is possible that replacing these neighboring hygroscopic VP repeat units with hydrophobic VA repeat units, could increase the physical stability of an amorphous solid dispersion without compromising the drug-polymer solubility. This knowledge could be used advantageously in future development of amorphous drug delivery systems as copolymers could be customized to provide optimal drug-polymer solubility and physical stability.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejps.2016.01.026 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Drug-Phospholipid Co-Amorphous Formulations: The Role of Preparation Methods and Phospholipid Selection.
Pharmaceutics
December 2024
Department of Pharmacy, Faculty of Health and Medical Science, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
: This study aims to broaden the knowledge on co-amorphous phospholipid systems (CAPSs) by exploring the formation of CAPSs with a broader range of poorly water-soluble drugs, celecoxib (CCX), furosemide (FUR), nilotinib (NIL), and ritonavir (RIT), combined with amphiphilic phospholipids (PLs), including soybean phosphatidylcholine (SPC), hydrogenated phosphatidylcholine (HPC), and mono-acyl phosphatidylcholine (MAPC). : The CAPSs were initially prepared at equimolar drug-to-phospholipid (PL) ratios by mechano-chemical activation-based, melt-based, and solvent-based preparation methods, i.e.
View Article and Find Full Text PDFIntensification of quercetin nanobubble formulation and performance by multi-factor optimization and interaction analysis.
Pharm Dev Technol
December 2024
Brilliant Grammar School Educational Society's Group of Institutions - Integrated Campus (Faculty of Engineering and Faculty of Pharmacy), Hyderabad, Telangana, India.
The natural flavonoid Quercetin (QT) showed a potential for various health benefits, but its pharmaceutical applications are hindered by low solubility, permeability, and limited bioavailability. This research aimed to synthesize, develop and optimize polylactic acid co-glycolic acid (PLGA) nanobubbles using solvent evaporation method as a sustained delivery system for QT, thus improving stability and bioavailability. Through a four-factor, three-level Box Behnken Design, 29 experimental runs were carried out to optimize QT-PLGA nanobubbles.
View Article and Find Full Text PDFHigh-Throughput Microarray Approaches for Predicting the Stability of Drug-Polymer Solid Dispersions.
Mol Pharm
January 2025
School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.
Amorphous solid dispersions (ASDs) offer a well-recognized strategy to improve the effective solubility and, hence, bioavailability of poorly soluble drugs. In this study, we developed an extensive library of a significant number of solid dispersion formulations using a library of chemically diverse drugs combined with a water-soluble polymer (polyvinylpyrrolidone vinyl acetate, PVPVA) at different loadings. These formulations were printed as microarrays of solid dispersion formulations, utilizing minimal material amounts (nanograms).
View Article and Find Full Text PDFImpact of HPMCAS Grade on the Release of Weakly Basic Drugs from Amorphous Solid Dispersions.
Mol Pharm
January 2025
Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States.
Oppositely charged species can form electrostatic interactions in aqueous solution, and these may lead to reduced solubility of the interacting components. Herein, insoluble complex formation between the lipophilic weakly basic drugs, cinnarizine or loratadine, and the enteric polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS), was studied and used to better understand drug and polymer release from their corresponding amorphous solid dispersions (ASDs). Surface area normalized release experiments were performed at various pH conditions for three different grades of HPMCAS, LF, MF and HF, as well as their ASDs.
View Article and Find Full Text PDFHigh drug-loaded amorphous solid dispersions of a poor glass forming drug: The impact of polymer type and cooling rate on amorphous drug behaviour.
Int J Pharm
December 2024
Pharmaceutical Engineering Group, Medical Biology Centre, 97, Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom. Electronic address:
Enhancing the aqueous solubility via amorphization of crystalline poor glass-forming drugs represents a challenge, particularly when drug dosing is high. In such scenarios, there is often a need for high polymer loadings, leading to an increase in the dosage form mass and less patient acceptability. This work investigated the role that polymer type and after-melt cooling rate had upon the amorphicity of solid dispersions (SDs) containing high levels of naproxen and three commonly used polymeric excipients: Eudragit® EPO, Kollidon® VA64, and Soluplus®.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!