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

scholarly journals Thermal Stability of Amorphous Solid Dispersions

Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 238
Author(s):  
Dijana Jelić
Keyword(s):  
Thermal Stability ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Pharmaceutical Products ◽  
Point Of View ◽  
Water Soluble ◽  
Amorphous Solid Dispersion ◽  
Thermal Stability Of

Amorphous solid dispersion drug delivery systems (ASD DDS) were proved to be efficient for the enhancement of solubility and bioavailability of poorly water-soluble drugs. One of the major keys for successful preparation of ASD is the selection of appropriate excipients, mostly polymers, which have a crucial role in improving drug solubility and its physical stability. Even though, excipients should be chemically inert, there is some evidence that polymers can affect the thermal stability of active pharmaceutical ingredients (API). The thermal stability of a drug is closely related to the shelf-life of pharmaceutical products and therefore it is a matter of high pharmaceutical relevance. An overview of thermal stability of amorphous solids is provided in this paper. Evaluation of thermal stability of amorphous solid dispersion is perceived from the physicochemical perspective, from a kinetic (motions) and thermodynamic (energy) point of view, focusing on activation energy and fragility, as well all other relevant parameters for ASD design, with a glance on computational kinetic analysis of solid-state decomposition.

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.

scholarly journals Applicability of an Experimental Grade of Hydroxypropyl Methylcellulose Acetate Succinate as a Carrier for Formation of Solid Dispersion with Indomethacin

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 353
Author(s):  
Hiroshi Ueda ◽  
Yuya Hirakawa ◽  
Hironori Tanaka ◽  
Tetsuya Miyano ◽  
Katsuji Sugita
Keyword(s):  
Solid Dispersion ◽  
Hydroxypropyl Methylcellulose ◽  
Principal Component ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Amorphous Solid Dispersion ◽  
Scanning Calorimetry ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Amorphous Drug

The transformation of a crystalline drug into an amorphous form is a promising way to enhance the oral bioavailability of poorly water-soluble drugs. Blending of a carrier, such as a hydrophilic polymer, with an amorphous drug is a widely used method to produce a solid dispersion and inhibit crystallization. This study investigates an experimental grade of hydroxypropyl methylcellulose acetate succinate, HPMCAS-MX (MX), as a solid dispersion carrier. Enhancement of thermal stability and reduction of the glass transition temperature (Tg) of MX compared with those of the conventional grade were evaluated through thermogravimetric analysis and differential scanning calorimetry (DSC). The formation of a homogeneous amorphous solid dispersion between MX and indomethacin was confirmed by X-ray powder diffraction analysis, DSC, and Raman mapping. It was observed that 10–30% MX did not act as an anti-plasticizer, but the utilization of >40% MX caused an increase in Tg and reduction of molecular mobility. This could be explained by a change in intermolecular interactions, inferred from infrared spectroscopy combined with principal component analysis. HPMCAS-MX exhibited similar performance to that of conventional-grade, HPMCAS-MG. Although HPMCAS-MX has thermal properties different from those of conventional-grade HPMCAS-MG, it retains its ability as a solid dispersion carrier.

scholarly journals In Vitro-In Silico Tools for Streamlined Development of Acalabrutinib Amorphous Solid Dispersion Tablets

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1257
Author(s):  
Deanna M. Mudie ◽  
Aaron M. Stewart ◽  
Jesus A. Rosales ◽  
Molly S. Adam ◽  
Michael M. Morgen ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
In Silico ◽  
Ph Effect ◽  
Hydroxypropyl Methylcellulose ◽  
Amorphous Solid ◽  
Dosage Forms ◽  
Water Soluble ◽  
Amorphous Solid Dispersion ◽  
In Silico Tools

Amorphous solid dispersion (ASD) dosage forms can improve the oral bioavailability of poorly water-soluble drugs, enabling the commercialization of new chemical entities and improving the efficacy and patient compliance of existing drugs. However, the development of robust, high-performing ASD dosage forms can be challenging, often requiring multiple formulation iterations, long timelines, and high cost. In a previous study, acalabrutinib/hydroxypropyl methylcellulose acetate succinate (HPMCAS)-H grade ASD tablets were shown to overcome the pH effect of commercially marketed Calquence in beagle dogs. This study describes the streamlined in vitro and in silico approach used to develop those ASD tablets. HPMCAS-H and -M grade polymers provided the longest acalabrutinib supersaturation sustainment in an initial screening study, and HPMCAS-H grade ASDs provided the highest in vitro area under the curve (AUC) in gastric to intestinal transfer dissolution tests at elevated gastric pH. In silico simulations of the HPMCAS-H ASD tablet and Calquence capsule provided good in vivo study prediction accuracy using a bottom–up approach (absolute average fold error of AUC0-inf < 2 except for Calquence + famotidine ≈ 3). This streamlined approach combined an understanding of key drug, polymer, and gastrointestinal properties with in vitro and in silico tools to overcome the acalabrutinib pH effect without the need for reformulation or multiple studies, showing promise for reducing time and costs to develop ASD drug products.

Amorphous solid dispersion technique for improved drug delivery: basics to clinical applications

2015 ◽  
Vol 5 (6) ◽  
pp. 552-565 ◽  
Author(s):  
Dinesh Kumar Mishra ◽  
Vinod Dhote ◽  
Arpit Bhargava ◽  
Dinesh Kumar Jain ◽  
Pradyumna Kumar Mishra
Keyword(s):  
Drug Delivery ◽  
Solid Dispersion ◽  
Amorphous Solid ◽  
Clinical Applications ◽  
Amorphous Solid Dispersion ◽  
Dispersion Technique

scholarly journals Preparation and Characterization of Artemether Solid Dispersion by Spray Drying Technique

2021 ◽  
Vol 11 (2) ◽  
pp. 1-5
Author(s):  
Dhiraj Dabhade ◽  
Kamlesh Wadher ◽  
Shrikant Bute ◽  
Nikita Naidu ◽  
Milind Umekar ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Spray Drying ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Study Data ◽  
Water Soluble ◽  
Amorphous Solid Dispersion ◽  
Scanning Calorimetry ◽  
Poorly Water Soluble

Introduction: Artemether, a BCS class IV drug (poorly water soluble and poorly permeable, less bioavailability) but is found to be effective against falciparum malaria. Preparation of water soluble formulation could be the technique to improve bioavailability of such drug. The most ideally used technique to enhance the solubility and dissolution of poorly water soluble drugs is Solid dispersion method. Method: The objective of the study was to enhance the solubility and dissolution rate of Artemether by preparing solid dispersions using Soluplus, at different ration of 1:1, 1:2, 1:3 and 1:4 using spray drying technology. Prepared Solid dispersions were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Results: The spray-dried solid dispersions found to be having less crystallinity and showed higher dissolution rates. Solubility study data showed the optimum drug/Soluplus ratio to be 1:3. The dissolution studies of Solid dispersions in 1.2 pH and 6.8 pH buffer showed higher drug release as compared to pure drug. Conclusion: Thus we conclude that an amorphous solid dispersion of Artemether could be a better option for enhancing the dissolution rate of drug Keywords: solid dispersion, artemether, soluplus, solubility enhancement

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.

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