Agglomerative crystallization of ABT‐510 in a partially miscible solvent system

Sheikh, Ahmad Y.; Pál, Ágnes; Viswanath, Shekhar K.; Tolle, John C.

doi:10.1002/jps.21063

Cited by 3 publications

(1 citation statement)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this is by no means a universal solution and at times may only offer marginal improvement. Yet another approach of spherical crystallization, which involves intentional controlled agglomeration during isolation/drying, can greatly improve physical properties. − Emulsion based crystallization processes to generate spherical agglomerates of API − offer another alternative. A recent study outlines spherical crystallization via quasi-emulsion solvent diffusion, antisolvent and pH shift .…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Co-processed APIs and Proposals for Enabling Commercialization of These Transformative Technologies

et al. 2020

View full text Add to dashboard Cite

Optimized physical properties (e.g., bulk, surface/interfacial, and mechanical properties) of active pharmaceutical ingredients (APIs) are key to the successful integration of drug substance and drug product manufacturing, robust drug product manufacturing operations, and ultimately to attaining consistent drug product critical quality attributes. However, an appreciable number of APIs have physical properties that cannot be managed via routes such as form selection, adjustments to the crystallization process parameters, or milling. Approaches to control physical properties in innovative ways offer the possibility of providing additional and unique opportunities to control API physical properties for both batch and continuous drug product manufacturing, ultimately resulting in simplified and more robust pharmaceutical manufacturing processes. Specifically, diverse opportunities to significantly enhance API physical properties are created if allowances are made for generating co-processed APIs by introducing nonactive components (e.g., excipients, additives, carriers) during drug substance manufacturing. The addition of a nonactive coformer during drug substance manufacturing is currently an accepted approach for cocrystals, and it would be beneficial if a similar allowance could be made for other nonactive components with the ability to modify the physical properties of the API. In many cases, co-processed APIs could enable continuous direct compression for small molecules, and longer term, this approach could be leveraged to simplify continuous end-to-end drug substance to drug product manufacturing processes for both small and large molecules. As with any novel technology, the regulatory expectations for co-processed APIs are not yet clearly defined, and this creates challenges for commercial implementation of these technologies by the pharmaceutical industry. The intent of this paper is to highlight the opportunities and growing interest in realizing the benefits of co-processed APIs, exemplified by a body of academic research and industrial examples. This work will highlight reasons why co-processed APIs would best be considered as drug substances from a regulatory perspective and emphasize the areas where regulatory strategies need to be established to allow for commercialization of innovative approaches in this area.

show abstract

Section: Introductionmentioning

confidence: 99%

Recent Advances in Co-processed APIs and Proposals for Enabling Commercialization of These Transformative Technologies

et al. 2020

View full text Add to dashboard Cite

show abstract

References

2023

Crystallization of Organic Compounds

View full text Add to dashboard Cite

A Co-Processed API Approach for a Shear Sensitive Compound Affording Improved Chemical Stability and Streamlined Drug Product Processing

Schenck¹,

Neri²,

Jia³

et al. 2021

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

The physical properties of active pharmaceutical ingredients (API) are critical to both drug substance (DS) isolation and drying operations, as well as streamlined drug product (DP) processing and the quality of final dosage units. High aspect ratio, low bulk density, API 'needles' in particular are a hindrance to efficient processing, with a low probability that conventional crystallization routes can modify the challenging morphology. The compound evaluated in this manuscript demonstrated this non-ideal morphology, with the added complexity of shear sensitivity. Modest shear exposure resulted in conversion of the thermodynamically stable crystalline phase to the amorphous phase, with the amorphous phase then undergoing accelerated chemical degradation. Slow filtration during DS isolation resulted in uncontrolled and elevated amorphous levels, while subsequent DP operations including blending, densification and compression increased amorphous content still further. A chemically stable final dosage unit would ideally involve a high bulk density, free flowing API that did not require densification in order to be commercialized as an oral dosage form with direct encapsulation of a single dosage unit. Despite every effort to modify the crystallization process, the physical properties of the API could not be improved. Here, an innovative isolation strategy using a thin film evaporation (TFE) process in the presence of a water soluble polymer alleviated filtration and drying risks and consistently achieved a high bulk density, free flowing co-processed API amenable to direct encapsulation. Characterization of the engineered materials suggested the lower amorphous levels and reduced shear sensitivity were achieved by coating surfaces of the API at relatively low polymer loads. This particle engineering route blurred conventional DS/DP boundaries that not only achieved improved chemical stability but also resulted in a optimized material, with simplified and more robust processing operations for both drug substance and drug product.

show abstract

Agglomerative crystallization of ABT‐510 in a partially miscible solvent system

Cited by 3 publications

References 17 publications

Recent Advances in Co-processed APIs and Proposals for Enabling Commercialization of These Transformative Technologies

Recent Advances in Co-processed APIs and Proposals for Enabling Commercialization of These Transformative Technologies

References

A Co-Processed API Approach for a Shear Sensitive Compound Affording Improved Chemical Stability and Streamlined Drug Product Processing

Contact Info

Product

Resources

About