Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Polymer Nanocoating of Amorphous Drugs for Improving Stability, Dissolution, Powder Flow, and Tabletability: The Case of Chitosan-Coated Indomethacin.

ABSTRACT: As a result of its higher molecular mobility, the surface of an amorphous drug can grow crystals much more rapidly than the bulk, causing poor stability and slow dissolution of drug products. We show that a nanocoating of chitosan (a pharmaceutically acceptable polymer) can be deposited on the surface of amorphous indomethacin by electrostatic deposition, leading to significant improvement of physical stability, wetting by aqueous media, dissolution rate, powder flow, and tabletability. The coating condition was chosen so that the positively charged polymer deposits on the negatively charged drug. Chitosan coating is superior to gelatin coating with respect to stability against crystallization and agglomeration of coated particles.

SUBMITTER: Li Y

PROVIDER: S-EPMC6404105 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Polymer Nanocoating of Amorphous Drugs for Improving Stability, Dissolution, Powder Flow, and Tabletability: The Case of Chitosan-Coated Indomethacin.

Li Yuhui Y Yu Junguang J Hu Shenye S Chen Zhenxuan Z Sacchetti Mark M Sun Changquan Calvin CC Yu Lian L

Molecular pharmaceutics 20190206 3

As a result of its higher molecular mobility, the surface of an amorphous drug can grow crystals much more rapidly than the bulk, causing poor stability and slow dissolution of drug products. We show that a nanocoating of chitosan (a pharmaceutically acceptable polymer) can be deposited on the surface of amorphous indomethacin by electrostatic deposition, leading to significant improvement of physical stability, wetting by aqueous media, dissolution rate, powder flow, and tabletability. The coat ...[more]

PMID: 30668120

Similar Datasets

The interplay of dissolution, solution crystallization and solid-state transformation of amorphous indomethacin in aqueous solution.

Project description:Supersaturation profiles of amorphous indomethacin in aqueous solution containing 0.4 wt% and 4 wt% of isopropanol were predicted by combining separately-determined kinetics for dissolution, solution crystallization, and solid-state transformation. The kinetics of solid-state transformation were measured and compared to various data from the literature. The proposed kinetic model accounts for dissolution, solution crystallization and amorphous-to-crystalline solid-state transformation. It was validated for different initial amounts of amorphous and crystalline material and systems with different isopropanol contents. Furthermore, the influence of polyethylene glycol on the supersaturation behavior was investigated. The results clearly show the robustness of the model and give insight into the interplay of dissolution, solution crystallization, and solid-state transformation of. In particular, the influence of solid-state transformation on the overall supersaturation profile was elucidated in a quantitative manner. An amorphicity function φ(t) is proposed to account for the kinetics of the solid-state transformation. Its general form could be derived consistently from different sets of experimental data and seems to be independent of the particle size of the amorphous material and hydrodynamic conditions. This work is among the first of its kind to successfully integrate dissolution, crystallization from solution and solid-state transformation in a model that shows good predictability.

| S-EPMC7725739 | biostudies-literature

Hydrogen Bonding in Amorphous Indomethacin.

Project description:Amorphous Indomethacin has enhanced bioavailability over its crystalline forms, yet amorphous forms can still possess a wide variety of structures. Here, Empirical Potential Structure Refinement (EPSR) has been used to provide accurate molecular models on the structure of five different amorphous Indomethacin samples, that are consistent with their high-energy X-ray diffraction patterns. It is found that the majority of molecules in amorphous Indomethacin are non-bonded or bonded to one neighboring molecule via a single hydrogen bond, in contrast to the doubly bonded dimers found in the crystalline state. The EPSR models further indicate a substantial variation in hydrogen bonding between different amorphous forms, leading to a diversity of chain structures not found in any known crystal structures. The majority of hydrogen bonds are associated with the carboxylic acid group, although a significant number of amide hydrogen bonding interactions are also found in the models. Evidence of some dipole-dipole interactions are also observed in the more structurally ordered models. The results are consistent with a distribution of Z-isomer intramolecular type conformations in the more disordered structures, that distort when stronger intermolecular hydrogen bonding occurs. The findings are supported by 1H and 2H NMR studies of the hydrogen bond dynamics in amorphous Indomethacin.

| S-EPMC11359274 | biostudies-literature

Effect of Drug-Polymer Interaction in Amorphous Solid Dispersion on the Physical Stability and Dissolution of Drugs: The Case of Alpha-Mangostin.

Project description:Improving drug solubility is necessary for formulations of poorly water-soluble drugs, especially for oral administration. Amorphous solid dispersions (ASDs) are widely used in the pharmaceutical industry to improve the physical stability and solubility of drugs. Therefore, this study aims to characterize interaction between a drug and polymer in ASD, as well as evaluate the impact on the physical stability and dissolution of alpha-mangostin (AM). AM was used as a model of a poorly water-soluble drug, while polyvinylpyrrolidone (PVP) and eudragit were used as polymers. The amorphization of AM-eudragit and AM-PVP was confirmed as having a halo pattern with powder X-ray diffraction measurements and the absence of an AM melting peak in the differential scanning calorimetry (DSC) curve. The solubility of amorphous AM increased in the presence of either eudragit or PVP due to amorphization and interactions of AM-polymer. Furthermore, FT-IR spectroscopy and in silico studies revealed hydrogen bond interactions between the carbonyl group of AM and the proton of eudragit as well as PVP. AM-eudragit with a ratio of 1:1 recrystallized after 7 days of storage at 25 °C and 90% RH, while the AM-PVP 1:4 and 1:10 samples retained the X-ray halo patterns, even under humid conditions. In a dissolution test, the presence of polymer in ASD significantly improved the dissolution profile due to the intermolecular interaction of AM-polymer. AM-eudragit 1:4 maintained AM supersaturation for a longer time compared to the 1:1 sample. However, a high supersaturation was not achieved in AM-PVP 1:10 due to the formation of large agglomerations, leading to a slow dissolution rate. Based on the results, interaction of AM-polymer in ASD can significantly improve the pharmaceutical properties of AM including the physical stability and dissolution.

| S-EPMC10384849 | biostudies-literature

Transcriptomics Library Data of Chitosan-coated Cavendish Banana

Project description:We report the first RNA sequencing data of 1.25% chitosan-coated and uncoated (control) fruit of Musa acuminata (AAA Group, Subgroup Cavendish) at unripe (day 1) and ripe (day 7) stage

2019-11-21 | GSE139457 | GEO

Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends.

Project description:The work evaluates the stability of amorphous and co-amorphous olanzapine (OLZ) in tablets manufactured by direct compression. The flowability and the compressibility of amorphous and co-amorphous OLZ with saccharin (SAC) and the properties of the tablets obtained were measured and compared to those of tablets made with crystalline OLZ. The flowability of the amorphous and mostly of the co-amorphous OLZ powders decreased in comparison with the crystalline OLZ due to the higher cohesiveness of the former materials. The stability of the amorphous and co-amorphous OLZ prior to and after tableting was monitored by XRPD, FTIR, and NIR spectroscopies. Tablets presented long-lasting amorphous OLZ with enhanced water solubility, but the release rate of the drug decreased in comparison with tablets containing crystalline OLZ. In physical mixtures made of crystalline OLZ and SAC, an extent of amorphization of approximately 20% was accomplished through the application of compaction pressures and dwell times of 155 MPa and 5 min, respectively. The work highlighted the stability of amorphous and co-amorphous OLZ during tableting and the positive effect of compaction pressure on the formation of co-amorphous OLZ, providing an expedited amorphization technique, given that the process development-associated hurdles were overcome.

| S-EPMC9332588 | biostudies-literature

Surface Stabilization and Dissolution Rate Improvement of Amorphous Compacts with Thin Polymer Coatings: Can We Have It All?

Project description:The distinction between surface and bulk crystallization of amorphous pharmaceuticals, as well as the importance of surface crystallization for pharmaceutical performance, is becoming increasingly evident. An emerging strategy in stabilizing the amorphous drug form is to utilize thin coatings at the surface. While the physical stability of systems coated with pharmaceutical polymers has recently been studied, the effect on dissolution performance as a function of storage time, as a further necessary step toward the success of these formulations, has not been previously studied. Furthermore, the effect of coating thickness has not been elucidated. This study investigated the effect of these polymer-coating parameters on the interplay between amorphous surface crystallization and drug dissolution for the first time. The study utilized simple tablet-like coated dosage forms, comprising a continuous amorphous drug core and thin polymer coating (hundreds of nanometers to a micrometer thick). Monitoring included analysis of both the solid-state of the model drug (with SEM, XRD, and ATR FTIR spectroscopy) and dissolution performance (and associated morphology and solid-state changes) after different storage times. Stabilization of the amorphous form (dependent on the coating thickness) and maintenance of early-stage intrinsic dissolution rates characteristic for the unaged amorphous drug were achieved. However, dissolution in the latter stages was likely inhibited by the presence of a polymer at the surface. Overall, this study introduced a versatile coated system for studying the dissolution of thin-coated amorphous dosage forms suitable for different drugs and coating agents. It demonstrated the importance of multiple factors that need to be taken into consideration when aiming to achieve both physical stability and improved release during the shelf life of amorphous formulations.

| S-EPMC7145361 | biostudies-literature

Improving anti-tumor activity of sorafenib tosylate by lipid- and polymer-coated nanomatrix.

Project description:In the present study, we select the Sylysia 350 (Sylysia) as mesoporous material, distearoylphosphatidylethanolamine-poly(ethylene glycol)2000 (DSPE-PEG) as absorption enhancer and hydroxy propyl methyl cellulose (HPMC) as crystallization inhibitor to prepare sorafenib tosylate (SFN) nanomitrix (MSNM@SFN) for improving the anti-tumor activity of SFN. The MSNM@SFN was prepared by solvent evaporation method. The solubility, dissolution, and bioavailability of SFN in MSNM@SFN were also investigated. The anti-tumor activity of MSNM@SFN was evaluated in vitro and in vivo. Our results indicated that the solubility and dissolution of SFN in MSNM@SFN were significantly increased. The oral bioavailability of SFN in MSNM@SFN was greatly improved 7.7-fold compared with that in SFN suspension. The enhanced anti-tumor activity of MSNM@SFN was confirmed in vitro and in vivo experiments. This nanomatrix developed in this study could be a promising drug delivery platform for improving the therapeutic efficacy of poorly water-soluble drugs.

| S-EPMC8241045 | biostudies-literature

Amorphous-Amorphous Phase Separation in API/Polymer Formulations.

Project description:The long-term stability of pharmaceutical formulations of poorly-soluble drugs in polymers determines their bioavailability and therapeutic applicability. However, these formulations do not only often tend to crystallize during storage, but also tend to undergo unwanted amorphous-amorphous phase separations (APS). Whereas the crystallization behavior of APIs in polymers has been measured and modeled during the last years, the APS phenomenon is still poorly understood. In this study, the crystallization behavior, APS, and glass-transition temperatures formulations of ibuprofen and felodipine in polymeric PLGA excipients exhibiting different ratios of lactic acid and glycolic acid monomers in the PLGA chain were investigated by means of hot-stage microscopy and DSC. APS and recrystallization was observed in ibuprofen/PLGA formulations, while only recrystallization occurred in felodipine/PLGA formulations. Based on a successful modeling of the crystallization behavior using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT), the occurrence of APS was predicted in agreement with experimental findings.

| S-EPMC6155819 | biostudies-literature

Stabilizing Mechanisms of β-Lactoglobulin in Amorphous Solid Dispersions of Indomethacin.

Project description:Proteins, and in particular whey proteins, have recently been introduced as a promising excipient class for stabilizing amorphous solid dispersions. However, despite the efficacy of the approach, the molecular mechanisms behind the stabilization of the drug in the amorphous form are not yet understood. To investigate these, we used experimental and computational techniques to study the impact of drug loading on the stability of protein-stabilized amorphous formulations. β-Lactoglobulin, a major component of whey, was chosen as a model protein and indomethacin as a model drug. Samples, prepared by either ball milling or spray drying, formed single-phase amorphous solid dispersions with one glass transition temperature at drug loadings lower than 40-50%; however, a second glass transition temperature appeared at drug loadings higher than 40-50%. Using molecular dynamics simulations, we found that a drug-rich phase occurred at a loading of 40-50% and higher, in agreement with the experimental data. The simulations revealed that the mechanisms of the indomethacin stabilization by β-lactoglobulin were a combination of (a) reduced mobility of the drug molecules in the first drug shell and (b) hydrogen-bond networks. These networks, formed mostly by glutamic and aspartic acids, are situated at the β-lactoglobulin surface, and dependent on the drug loading (>40%), propagated into the second and subsequent drug layers. The simulations indicate that the reduced mobility dominates at low (<40%) drug loadings, whereas hydrogen-bond networks dominate at loadings up to 75%. The computer simulation results agreed with the experimental physical stability data, which showed a significant stabilization effect up to a drug fraction of 70% under dry storage. However, under humid conditions, stabilization was only sufficient for drug loadings up to 50%, confirming the detrimental effect of humidity on the stability of protein-stabilized amorphous formulations.

| S-EPMC9644381 | biostudies-literature

Mineral dissolution and reprecipitation mediated by an amorphous phase.

Project description:Fluid-mediated mineral dissolution and reprecipitation processes are the most common mineral reaction mechanism in the solid Earth and are fundamental for the Earth's internal dynamics. Element exchange during such mineral reactions is commonly thought to occur via aqueous solutions with the mineral solubility in the coexisting fluid being a rate limiting factor. Here we show in high-pressure/low temperature rocks that element transfer during mineral dissolution and reprecipitation can occur in an alkali-Al-Si-rich amorphous material that forms directly by depolymerization of the crystal lattice and is thermodynamically decoupled from aqueous solutions. Depolymerization starts along grain boundaries and crystal lattice defects that serve as element exchange pathways and are sites of porosity formation. The resulting amorphous material occupies large volumes in an interconnected porosity network. Precipitation of product minerals occurs directly by repolymerization of the amorphous material at the product surface. This mechanism allows for significantly higher element transport and mineral reaction rates than aqueous solutions with major implications for the role of mineral reactions in the dynamic Earth.

| S-EPMC5915427 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data