A novel co-processing method to manufacture an API for extended release formulation via formation of agglomerates of active ingredient and hydroxypropyl methylcellulose during crystallization

Rosenbaum, Tamar; Erdemir, Deniz; Chang, Shih‐Ying; Kientzler, Don; Wang, Steve; Chan, Stephen; Brown, Jonathan; Hanley, Sarah; Kiang, San

doi:10.1080/03639045.2018.1483386

Cited by 10 publications

(6 citation statements)

References 18 publications

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“…Particle size increased as a result of co-processing. This is consistent with the findings of other studies carried out involving co-processing where the co-processed excipient developed had a larger particle size relative to the constituent excipients 35,36 . The angle of repose values was ranked in the following order, CPE<MCC<CPV, with CPE having a value of 18.23 º and CPV having a value of 43.90 º.…”

Section: Powder Propertiessupporting

confidence: 92%

Development and Characterization of a Microcrystalline Cellulose-based co-Processed Excipient using Design of Experiment Approach

Haruna

Apeji

Oyi

2022

Jordan j. pharm. sci.

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The study aims to develop a co-processed excipient (CPE) containing microcrystalline cellulose (MCC) and crospovidone (CPV) using the wet massing technique. Preformulation studies were carried out on CPE to characterize its physicochemical properties. Optimization of the formulation of CPE was carried out using a mixture of experimental designs. The optimization study suggested a composite excipient containing MCC (99 %) and CPV (1 %). Solid state characterization of CPE revealed a material that is predominantly crystalline in nature. The particle size of CPE increased in comparison to starting material. FT-IR confirmed the compatibility of MCC and CPV when co-processed together to yield a single composite excipient. There was a decrease in moisture content and moisture sorption capacity of CPE when compared to MCC. Powder characterization revealed an improvement in bulk flow properties of CPE relative to MCC. In summary, the physicochemical properties obtained suggest that CPE will be a suitable tableting excipient in solid dosage formulation by direct compression.

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Section: Powder Propertiessupporting

confidence: 92%

Development and Characterization of a Microcrystalline Cellulose-based co-Processed Excipient using Design of Experiment Approach

Haruna

Apeji

Oyi

2022

Jordan j. pharm. sci.

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“…In the paper by Rosenbaum T et al, an API (a commercial confidential compound manufactured by Bristol Myers Squibb) was selected as the model drug, dissolved in water, and HPMC was add as a modifier to the API solution. They were co-processed by CCA, and the ratio of API to HPMC was 3:1 [ 94 ]. Compared to the pure API, the co-processed product showed improved flow properties and sustained release behavior.…”

Section: Hpmc (Hydroxypropyl Methylcellulose)mentioning

confidence: 99%

Surface Modifiers on Composite Particles for Direct Compaction

Chen

Liu²,

Zhu³

et al. 2022

Pharmaceutics

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Direct compaction (DC) is considered to be the most effective method of tablet production. However, only a small number of the active pharmaceutical ingredients (APIs) can be successfully manufactured into tablets using DC since most APIs lack adequate functional properties to meet DC requirements. The use of suitable modifiers and appropriate co-processing technologies can provide a promising approach for the preparation of composite particles with high functional properties. The purpose of this review is to provide an overview and classification of different modifiers and their multiple combinations that may improve API tableting properties or prepare composite excipients with appropriate co-processed technology, as well as discuss the corresponding modification mechanism. Moreover, it provides solutions for selecting appropriate modifiers and co-processing technologies to prepare composite particles with improved properties.

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“…5,38−42 The improvement in the tableting properties of these agglomerates is mainly due to the increased particle size of co-processed particles compared to that of API alone and changes in particle shape from needle-like or platelike to nearly spheroidal. This concept was extended for preparation of API and excipient agglomerates of highly watersoluble drugs to improve flow and compaction properties, 43,44 where the APIs were crystallized in the presence of polymers and agglomeration was achieved by relying on swelling behavior of polymers in water/organic mixtures. Another example of precipitating API in the presence of excipients is the method developed to manufacture amorphous formulations of high-melting and low-solubility compounds, where both hot melt extrusion and spray drying are not options.…”

Section: ■ Routes To Generate Co-processed Apimentioning

confidence: 99%

“…Crystallo- co -agglomeration, a variation of the spherical crystallization technique wherein the drug is crystallized and agglomerated in the presence of a material via the use of an antisolvent and bridging liquid, has been demonstrated on numerous drugs to improve tableting properties and allow for direct compression. ,− The improvement in the tableting properties of these agglomerates is mainly due to the increased particle size of co-processed particles compared to that of API alone and changes in particle shape from needle-like or plate-like to nearly spheroidal. This concept was extended for preparation of API and excipient agglomerates of highly water-soluble drugs to improve flow and compaction properties, , where the APIs were crystallized in the presence of polymers and agglomeration was achieved by relying on swelling behavior of polymers in water/organic mixtures.…”

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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A novel co-processing method to manufacture an API for extended release formulation via formation of agglomerates of active ingredient and hydroxypropyl methylcellulose during crystallization

Cited by 10 publications

References 18 publications

Development and Characterization of a Microcrystalline Cellulose-based co-Processed Excipient using Design of Experiment Approach

Development and Characterization of a Microcrystalline Cellulose-based co-Processed Excipient using Design of Experiment Approach

Surface Modifiers on Composite Particles for Direct Compaction

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

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