Design and Scale-up of a Co-processing Technology to Improve Powder Properties of Drug Substances

Erdemir, Deniz; Daftary, Vivek; Lindrud, Mark; Buckley, David; Lane, Gregory C.; Malsbury, Adriene; Tao, Jing; Kopp, Nathaniel; Hsieh, Daniel; Nikitczuk, Whitney; Engstrom, Joshua D.

doi:10.1021/acs.oprd.9b00354

Cited by 14 publications

(8 citation statements)

References 21 publications

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“…The coprocessing method does not induce chemical interactions so that the co-processed excipients formed can be considered safe to use and therefore do not require additional toxicological studies, which will save manufacturing time. Another advantage of using the co-processing method in making excipients is that the co-processed excipients will cover each other's shortcomings and increase GM's stability, solubility, and gelling properties (Erdemir et al, 2019;Narang & Boddu, 2015) The co-process method helps to optimize the physical properties of each excipient. For example, stabilization of GM gels can be achieved by combining them with other polysaccharides such as xanthan gum using a freeze-drying method that results in controlled drug release (Abbaszadeh et al, 2016).…”

Section: Combination Of Gm With Other Polymersmentioning

confidence: 99%

Modifications and Pharmaceutical Applications of Glucomannan as Novel Pharmaceutical Excipient in Indonesia: Review Article

Aanisah

Wardhana²,

Chaerunisaa³

2022

J. Pharm. Sci. Clin. Res.

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<p>Currently, Indonesia is excessively dependent on imported raw materials, such as pharmaceutical excipients. In this regard, the current pandemic should remind the critical nature of independence in purchasing raw resources to cope with future dynamics. One of the causes of dependence is the lack of raw materials management, specifically from biological sources abundantly available. A significant advantage is directed towards natural excipients because large quantities of more affordable plants ensure sustained availability in nature. Therefore, this study highlighted the possibility of using excipients derived from natural resources that are commonly used yet underutilized in Indonesia, such as glucomannan (GM). Indonesia has the potential to produce GM, considering the high natural resources as its source. However, it has not been applied extensively in pharmaceutical preparations due to diverse uses in several countries' drug, food, and cosmetic industries. This study aimed to discuss the modifications of GM and their use as pharmaceutical excipients with better physical properties. Additionally, the potential of melinjo seeds that have not been widely used was also analyzed. Melinjo seeds can be used as a source of GM due to their fairly large polysaccharide of about 64.11%. This issue will promote national autonomy in developing novel pharmaceutical excipients derived from natural resources that are highly economical and innovative.</p>

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Section: Combination Of Gm With Other Polymersmentioning

confidence: 99%

Modifications and Pharmaceutical Applications of Glucomannan as Novel Pharmaceutical Excipient in Indonesia: Review Article

Aanisah

Wardhana²,

Chaerunisaa³

2022

J. Pharm. Sci. Clin. Res.

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“…Furthermore, the co-processed theophylline particles were formulated into a blend at 50−90% loading and successfully processed by direct compression. 51 There have been reports of using microfluidics to generate monodisperse drug-excipient spherical microparticles. 52,53 In this method, drug-excipient loaded droplets are generated using a microfluidic T-junction, before the droplets are transferred via a short tube to the collection vessel, which contains an excess of ultrapure water as the extraction medium.…”

Section: ■ Routes To Generate Co-processed Apimentioning

confidence: 99%

“…Scalability was demonstrated up to 50 kg scale in the pilot plant. Furthermore, the co-processed theophylline particles were formulated into a blend at 50–90% loading and successfully processed by direct compression …”

Section: Routes To Generate Co-processed Apimentioning

confidence: 99%

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

et al. 2020

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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.

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“…18,19 Crystallization or precipitation combined with nonactive components, while not changing API morphology, can achieve agglomeration to improve powder flow, tableting properties and ease of direct compression. [20][21][22][23]46 Coating of an API with excipients can have a profound effect on flow and compaction properties, 24−28 though these coating operations applied during dry powder processing generally involve the use of a high shear process. For the compound in question, this approach would not be viable due to shear sensitivity.…”

Section: Introductionmentioning

confidence: 99%

“…29 These processes can be robust, scalable and can achieve particles with improved compaction behavior and high drug loads. 23 The body of work presented here focuses on a compound where the thermodynamically stable crystalline phase presented an exceedingly problematic needle-like morphology, with primary particles in the 5-10 mm range. These particles could not be managed despite exhaustive exploration of the crystallization process design.…”

Section: Introductionmentioning

confidence: 99%

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

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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.

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Design and Scale-up of a Co-processing Technology to Improve Powder Properties of Drug Substances

Cited by 14 publications

References 21 publications

Modifications and Pharmaceutical Applications of Glucomannan as Novel Pharmaceutical Excipient in Indonesia: Review Article

Modifications and Pharmaceutical Applications of Glucomannan as Novel Pharmaceutical Excipient in Indonesia: Review Article

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

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

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