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Impact of Physicochemical Properties of Cellulosic Polymers on Supersaturation Maintenance in Aqueous Drug Solutions

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Abstract

The precipitation inhibitory effect of cellulosic polymers in relation to their physicochemical properties was studied. Using a poorly water-soluble model drug, griseofulvin, the precipitation inhibitory effect of a series of hydroxypropyl methylcellulose (HPMC) and methylcellulose polymers was studied using solvent–shift method. The extent of supersaturation maintenance of each polymer was then quantified by the parameter, supersaturation factor (SF). Partial least square (PLS) regression analysis was employed to understand the relative contribution from viscosity, hydroxypropyl content (HC), methoxyl content, methoxyl/hydroxypropyl ratio, and drug–polymer interaction parameter (χ) on SF. All grades of cellulosic polymers effectively prolonged supersaturation of griseofulvin. PLS regression analysis revealed that HC and χ appeared to have the strongest influence on SF response. A regression model of SF = 1.65–0.16 χ + 0.05 HC with a high correlation coefficient, r of 0.921, was obtained. Since the value of χ is inversely related to the strength of drug–polymer interaction, the result shows that SF increases with increasing drug–polymer interaction and increasing HC. As such, it can be implied that strong drug–polymer interaction and presence of hydroxypropyl groups in cellulosic polymers for hydrogen bonding are two key parameters for effective supersaturation maintenance. This knowledge on the relative contribution of polymer physicochemical properties on precipitation inhibition will allow the selection of suitable cellulosic polymers for systematic development of supersaturating drug delivery systems.

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Acknowledgements

Shiqi Hong acknowledges Roquette Asia Pacific Pte Ltd. for supporting the time taken for the manuscript preparation.

Funding

This work was funded by AbbVie Private Limited, Singapore.

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  1. Shiqi Hong

    Present address: Research and Development, Roquette Asia Pacific Pte. Ltd., 11 Biopolis Way, Helios #05-06, Singapore, 138667, Singapore

Authors and Affiliations

  1. GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore

    Shiqi Hong & Chan Lai Wah

  2. Drug Product Development, Research and Development, Abbvie Inc., 1 Waukegan Road, North Chicago, Illinois, USA

    Steven A. Nowak

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  1. Shiqi Hong
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Correspondence to Chan Lai Wah.

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Conflict of Interest

Hong Shiqi is an ex-employee of AbbVie Private Limited, Singapore and Steven A. Nowak is an employee of AbbVie, Inc. and may own AbbVie stock/options. AbbVie participated in the design, study conduct, interpretation of data, review, and approval of the publication. The authors declare no conflict of interest.

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Hong, S., Nowak, S.A. & Wah, C.L. Impact of Physicochemical Properties of Cellulosic Polymers on Supersaturation Maintenance in Aqueous Drug Solutions. AAPS PharmSciTech 19, 1860–1868 (2018). https://doi.org/10.1208/s12249-018-0999-y

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  • DOI: https://doi.org/10.1208/s12249-018-0999-y

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