Structural Characterization of Amorphous Solid Dispersions

Paudel, Amrit; Meeus, Joke; Mooter, Guy Van den

doi:10.1007/978-1-4939-1598-9_14

Cited by 16 publications

(23 citation statements)

References 319 publications

(191 reference statements)

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“…The hygroscopicity of the polymer in ASD and the hydrophobicity of the drug can potentially influence its moisture sorption and stability depending on the drug–polymer ratio and exposure to moisture during storage. Polymers with low hygroscopicity are preferred in the order of Eudragit/HPMC-AS < HPMC/Soluplus < copovidone < povidone [ 68 , 69 ]. In the authors’ work (unpublished results), ASDs containing 30% drug and 70% HPMC (ASD 1) or 70% Soluplus (ASD 2), respectively, were stable amorphous powders at ambient conditions of storage.…”

Section: Product Development Strategymentioning

confidence: 99%

“…The Ising model [ 68 ] is a simple description of two or more interacting systems with an interaction strength function, J J = (ϵAA + ϵBB − 2ϵAB)/4 where ϵ is the interaction energy between same (AA, BB) or different species (AB). The free energy change arising from such an interaction is described by the Flory–Huggins theory based on entropy of mixing of polymer dissolved in a solvent [ 69 ].…”

Section: Product Development Strategymentioning

confidence: 99%

“…Thermal techniques are classical methods for ASD characterization with DSC and mDSC commonly used for detection of desorption, T g , (re)crystallization, melting and decomposition. mDSC is particularly useful for separating the overlapping thermal events and T g evaluation [ 68 ]. Thermal methods with more elaborate cycling regimes can provide information on ASD formation and stability.…”

Section: Product Development Strategymentioning

confidence: 99%

See 2 more Smart Citations

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

Iyer¹,

Jovanovska

Berginc

et al. 2021

Pharmaceutics

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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.

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Section: Product Development Strategymentioning

confidence: 99%

Section: Product Development Strategymentioning

confidence: 99%

Section: Product Development Strategymentioning

confidence: 99%

See 1 more Smart Citation

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

Iyer¹,

Jovanovska

Berginc

et al. 2021

Pharmaceutics

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show abstract

“…As the fluid-state properties of polymers acting as the API solvent are challenging to establish, experimentally determined solid-solubility are often severely over-or underestimated. Therefore, a high resolution characterization using solid-state NMR spectroscopy/relaxometry and/or X-ray diffuse scattering analysis is necessary to verify the accuracy of the estimated solubility/miscibility (54). Moreover, experimental drug-polymer miscibility studies can generally be complemented by theoretical modeling, e.g., Flory-Huggins lattice theory and perturbed-chain statistical associating fluid theory (PC-SAFT) (44).…”

Section: Stability Assessment and Predictionmentioning

confidence: 99%

Developing HME-Based Drug Products Using Emerging Science: a Fast-Track Roadmap from Concept to Clinical Batch

et al. 2020

Self Cite

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This paper presents a rational workflow for developing enabling formulations, such as amorphous solid dispersions, via hot-melt extrusion in less than a year. First, our approach to an integrated product and process development framework is described, including state-ofthe-art theoretical concepts, modeling, and experimental characterization described in the literature and developed by us. Next, lab-scale extruder setups are designed (processing conditions and screw design) based on a rational, model-based framework that takes into account the thermal load required, the mixing capabilities, and the thermo-mechanical degradation. The predicted optimal process setup can be validated quickly in the pilot plant. Lastly, a transfer of the process to any GMP-certified manufacturing site can be performed in silico for any extruder based on our validated computational framework. In summary, the proposed workflow massively reduces the risk in product and process development and shortens the drug-to-market time for enabling formulations.

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“…The single Tg indicates miscibility, i.e., one of the co-amorphous components acts as a crystallization inhibitor for the other [ 21 ]. Modulated Differential Scanning Calorimetry (mDSC) has also been used, as it solves the problem of overlapping thermal transitions [ 55 , 57 , 58 , 59 ]. The Tg of a binary co-amorphous SD tends to be closer to the excess component and is usually increased compared to the individual amorphous components, indicating stability and a reduced crystallization tendency [ 5 , 17 ].…”

Section: Solid State Characterizationmentioning

confidence: 99%

Co-Amorphous Solid Dispersions for Solubility and Absorption Improvement of Drugs: Composition, Preparation, Characterization and Formulations for Oral Delivery

2018

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The amorphous solid state offers an improved apparent solubility and dissolution rate. However, due to thermodynamic instability and recrystallization tendencies during processing, storage and dissolution, their potential application is limited. For this reason, the production of amorphous drugs with adequate stability remains a major challenge and formulation strategies based on solid molecular dispersions are being exploited. Co-amorphous systems are a new formulation approach where the amorphous drug is stabilized through strong intermolecular interactions by a low molecular co-former. This review covers several topics applicable to co-amorphous drug delivery systems. In particular, it describes recent advances in the co-amorphous composition, preparation and solid-state characterization, as well as improvements of dissolution performance and absorption are detailed. Examples of drug-drug, drug-carboxylic acid and drug-amino acid co-amorphous dispersions interacting via hydrogen bonding, π−π interactions and ionic forces, are presented together with corresponding final dosage forms.

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Structural Characterization of Amorphous Solid Dispersions

Cited by 16 publications

References 319 publications

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

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

Developing HME-Based Drug Products Using Emerging Science: a Fast-Track Roadmap from Concept to Clinical Batch

Co-Amorphous Solid Dispersions for Solubility and Absorption Improvement of Drugs: Composition, Preparation, Characterization and Formulations for Oral Delivery

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