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The effect of cellulose derivatives on paracetamol crystallinity reduction

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Abstract

The amorphous forms of most active pharmaceutical substances are widely applied in solid dosage form technology because they are characterized by a better solubility and dissolution rate than their crystalline forms. With the amorphization of a crystalline active substance being the greatest challenge to be overcome in pharmaceutical technology, the aim of this study was to assess to what extent polymeric excipients such as cellulose derivatives affect the crystallinity of paracetamol, over-the-counter analgesic and antipyretic substance. To realize this purpose, binary physical mixtures containing 10, 30, 50, 70 and 90% of paracetamol were gently homogenized in a porcelain mortar with cellulose derivatives such as four kinds of hydroxypropyl methyl cellulose (HPMC) differing in their molecular masses and methylcellulose (MC). Differential scanning calorimetry (DSC) and spectroscopic techniques like Fourier transform infrared (FTIR) and Raman were applied as tools for evaluating the degree of paracetamol crystallinity reduction. The findings of these experiments revealed that cellulose derivatives do indeed reduce the degree of paracetamol crystallinity; however, the effect of the particular polymeric excipients did not show any statistically significant difference. Formation of metastable modification III of paracetamol was also confirmed, a modification which can be created in mixtures containing at least 10% of cellulose derivatives. In brief, all the HPMCs and MC examined affect the crystallinity of paracetamol to a similar degree. Furthermore, the degree of active substance crystallinity decreases as the content of cellulose derivatives in the mixture increases.

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Acknowledgements

This research was funded by the Ministry of Science and Higher Education, Poland, Grant Number 02-0015/07/505.

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  1. Department of Analytical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Gen. J. Hallera 107, 80-416, Gdansk, Poland

    Edyta Leyk & Marek Wesolowski

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EL helped in conceptualization, methodology, software, formal analysis, investigation, data curation, writing–original draft preparation, writing–review and editing. MW performed conceptualization, writing–original draft preparation, writing–review and editing, supervision. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Marek Wesolowski.

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Leyk, E., Wesolowski, M. The effect of cellulose derivatives on paracetamol crystallinity reduction. J Therm Anal Calorim 147, 10037–10048 (2022). https://doi.org/10.1007/s10973-022-11312-9

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