scholarly journals Amorphous Solid Dispersions (ASDs): The Influence of Material Properties, Manufacturing Processes and Analytical Technologies in Drug Product Development

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1682
Author(s):  
Raman Iyer ◽  
Vesna Petrovska Petrovska Jovanovska ◽  
Katja Berginc ◽  
Miha Jaklič ◽  
Flavio Fabiani ◽  
...  
Keyword(s):  
Material Properties ◽  
Drug Product ◽  
Solid Dispersions ◽  
Unmet Need ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Manufacturing Processes ◽  
Amorphous Solid Dispersions ◽  
Significant Challenge ◽  
Patient Centric

Poorly water-soluble drugs pose a significant challenge to developability due to poor oral absorption leading to poor bioavailability. Several approaches exist that improve the oral absorption of such compounds by enhancing the aqueous solubility and/or dissolution rate of the drug. These include chemical modifications such as salts, co-crystals or prodrugs and physical modifications such as complexation, nanocrystals or conversion to amorphous form. Among these formulation strategies, the conversion to amorphous form has been successfully deployed across the pharmaceutical industry, accounting for approximately 30% of the marketed products that require solubility enhancement and making it the most frequently used technology from 2000 to 2020. This article discusses the underlying scientific theory and influence of the active compound, the material properties and manufacturing processes on the selection and design of amorphous solid dispersion (ASD) products as marketed products. Recent advances in the analytical tools to characterize ASDs stability and ability to be processed into suitable, patient-centric dosage forms are also described. The unmet need and regulatory path for the development of novel ASD polymers is finally discussed, including a description of the experimental data that can be used to establish if a new polymer offers sufficient differentiation from the established polymers to warrant advancement.

scholarly journals Myth or Truth: The Glass Forming Ability Class III Drugs Will Always Form Single-Phase Homogenous Amorphous Solid Dispersion Formulations

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 529 ◽  
Author(s):  
Piyush Panini ◽  
Massimiliano Rampazzo ◽  
Abhishek Singh ◽  
Filip Vanhoutte ◽  
Guy Van den Mooter
Keyword(s):  
Single Phase ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Glass Forming Ability ◽  
Amorphous Solid Dispersion ◽  
Class Iii ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
Modulated Differential Scanning Calorimetry ◽  
Glass Forming

The physical stability of amorphous solid dispersions (ASD) of active pharmaceutical ingredients (APIs) of high glass forming ability (GFA class III) is generally expected to be high among the scientific community. In this study, the ASD of ten-selected class III APIs with the two polymers, PVPVA 64 and HPMC-E5, have been prepared by spray-drying, film-casting, and their amorphicity at T0 was investigated by modulated differential scanning calorimetry and powder X-ray diffraction. It was witnessed that only five out of ten APIs form good quality amorphous solid dispersions with no phase separation and zero crystalline content, immediately after the preparation and drying process. Hence, it was further established that the classification of an API as GFA class III does not guarantee the formulation of single phase amorphous solid dispersions.

scholarly journals Calibration-Free Second Harmonic Generation (SHG) Image Analysis for Quantification of Trace Crystallinity Within Final Dosage Forms of Amorphous Solid Dispersions

2018 ◽  
Vol 72 (11) ◽  
pp. 1594-1605 ◽  
Author(s):  
Casey J. Smith ◽  
Janny Dinh ◽  
Paul D. Schmitt ◽  
Paul A. Stroud ◽  
Jeremy Hinds ◽  
...  
Keyword(s):  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Dynamic Range ◽  
Second Harmonic ◽  
Solid Dispersions ◽  
Simulated Data ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Amorphous Solid Dispersions ◽  
Particle Counting

A statistical model enables auto-calibration of second harmonic generation (SHG) images for quantifying trace crystallinity within amorphous solid dispersions (ASDs) over a wide dynamic range of crystallinity. In this paper, we demonstrate particle-counting approaches for quantifying trace crystallinity, combined with analytical expressions correcting for particle overlap bias in higher crystallinity regimes to extend the continuous dynamic range of standard particle-counting algorithms through to the signal averaging regime. The reliability of the values recovered by these expressions was demonstrated with simulated data as well as experimental data obtained for an amorphous solid dispersion formulation containing evacetrapib, an Eli Lilly and Company compound. Since particle counting independently recovers the crystalline volume and the SHG intensity, the average SHG intensity per unit volume can be used as an internal calibrant for quantifying crystallinity at higher volume fractions, for which particle counting is no longer applicable.

scholarly journals Generation of high drug loading amorphous solid dispersions by Spray Drying

2018 ◽  
Author(s):  
Bhianca Lins de Azevedo Costa ◽  
Martial Sauceau ◽  
Romain Sescousse ◽  
Maria Ines Re
Keyword(s):  
Spray Drying ◽  
Drug Carrier ◽  
Drug Loading ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Drug Solubility ◽  
Amorphous Solid Dispersions ◽  
High Drug ◽  
High Drug Loading

Amorphous solid dispersions (ASDs) refers to drug - carrier systems, where the drug is dispersed in the carrier at a molecular level. In this work, ASDs were formulated by spray drying. The aim was to achieve high drug loads of an amorphous hydrophobic drug (Efavirenz - EFV) in  the  carrier Soluplus®. Solid state characterizations (mDSC, XRPD, DVS, Raman, SEM, stability and solubility studies) were done. EFV amorphisation in ASDs (20 to 85% EFV loads) resulted in improved drug solubility compared to unprocessed EFV crystals and tendency of properties evolution over time for ASDs with EFV loads  higher than 70 wt%. Keywords: amorphous solid dispersion, spray drying, high drug loading, soluplus, efavirenz.

Impact of incorporated drugs on material properties of amorphous solid dispersions

2021 ◽  
Vol 159 ◽  
pp. 88-98
Author(s):  
Karsten Flügel ◽  
Katharina Schmidt ◽  
Lena Mareczek ◽  
Michael Gäbe ◽  
Robert Hennig ◽  
...  
Keyword(s):  
Material Properties ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions

Development of novel darunavir amorphous solid dispersions with mesoporous carriers

2021 ◽  
Vol 159 ◽  
pp. 105700
Author(s):  
Sergey A. Zolotov ◽  
Natalia B. Demina ◽  
Anna S. Zolotova ◽  
Natalia V. Shevlyagina ◽  
Grigorii A. Buzanov ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions

Effect of Carrier Type and Tween® 80 Concentration on the Release of Silymarin from Amorphous Solid Dispersions

2021 ◽  
pp. 102416
Author(s):  
Valentyn Mohylyuk ◽  
Thomas Pauly ◽  
Oleksandr Dobrovolnyi ◽  
Nathan Scott ◽  
David S. Jones ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions

scholarly journals Enhanced Oral Bioavailability of Resveratrol by Using Neutralized Eudragit E Solid Dispersion Prepared via Spray Drying

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 90
Author(s):  
Eun-Sol Ha ◽  
Du Hyung Choi ◽  
In-hwan Baek ◽  
Heejun Park ◽  
Min-Soo Kim
Keyword(s):  
Spray Drying ◽  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Pharmaceutical Products ◽  
In Vitro Dissolution ◽  
Dependent Manner ◽  
Amorphous Solid Dispersions ◽  
Eudragit E

In this study, we designed amorphous solid dispersions based on Eudragit E/HCl (neutralized Eudragit E using hydrochloric acid) to maximize the dissolution of trans-resveratrol. Solid-state characterization of amorphous solid dispersions of trans-resveratrol was performed using powder X-ray diffraction, scanning electron microscopy, and particle size measurements. In addition, an in vitro dissolution study and an in vivo pharmacokinetic study in rats were carried out. Among the tested polymers, Eudragit E/HCl was the most effective solid dispersion for the solubilization of trans-resveratrol. Eudragit E/HCl significantly inhibited the precipitation of trans-resveratrol in a pH 1.2 dissolution medium in a dose-dependent manner. The amorphous Eudragit E/HCl solid dispersion at a trans-resveratrol/polymer ratio of 10/90 exhibited a high degree of supersaturation without trans-resveratrol precipitation for at least 48 h by the formation of Eudragit E/HCl micelles. In rats, the absolute oral bioavailability (F%) of trans-resveratrol from Eudragit E/HCl solid dispersion (10/90) was estimated to be 40%. Therefore, trans-resveratrol-loaded Eudragit E/HCl solid dispersions prepared by spray drying offer a promising formulation strategy with high oral bioavailability for developing high-quality health supplements, nutraceutical, and pharmaceutical products.

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