Регуляторные исследования и экспертиза лекарственных средств (Sep 2023)

NMR Spectroscopy Study of the Effect of the Molecular Mass of Hypromellose Phthalate on Its Solubility

  • S. V. Moiseev,
  • N. E. Kuz’mina,
  • E. Yu. Severinova,
  • N. D. Bunyatyan,
  • V. A. Evteev

DOI
https://doi.org/10.30895/1991-2919-2023-541
Journal volume & issue
Vol. 13, no. 3
pp. 385 – 393

Abstract

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Scientific relevance. Hypromellose phthalate is used in enteric coatings for oral medicinal products. The proportion of phthalate groups in the polymer is standardised because it has a significant effect on solubility. Whereas, the molecular mass of hypromellose phthalate is not controlled, and its impact on solubility in media with different pH values is understudied.Aim. The study aimed to employ NMR spectroscopy to investigate the effect the molecular mass of hypromellose phthalate may have on the dissolution kinetics at the pH value declared by the polymer manufacturer.Materials and methods. The study analysed hypromellose phthalate isolated from proton-pump inhibitor enteric coatings and the hypromellose phthalate reference standard. The molecular mass of the polymer was estimated by diffusion-ordered NMR spectroscopy (DOSY) with polyethylene glycols of known molecular masses for calibration. The authors studied the dissolution profiles of hypromellose phthalates of different molecular masses using 1H NMR spectra.Results. The authors developed a procedure for estimating the average molecular mass of hypromellose phthalate by DOSY. The procedure showed variations in the molecular mass of the polymer in the test samples; the molecular mass scatter amounted to 10 kDa. The dissolution profile of the test samples in an aqueous buffer solution (pH 5.59) was described by a linear function during the first hour. The slope characterising the dissolution rate varied from 10° to 36°.Conclusions. The variation in the molecular mass of hypromellose phthalate significantly affects the dissolution rate of the test samples. The function of the dissolution rate against the molecular mass of hypromellose phthalate is non-linear. The article provides a compelling reason for further research to derive a correlation equation for the dissolution rate of hypromellose phthalate as a function of two variables (molecular mass and proportion of phthalate groups in the polymer).

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