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Effect of poly(vinylpyrrolidone) or sodium alginate on the stability of the amorphous form of nimesulide

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Abstract

Nimesulide is a non-steroidal anti-inflammatory drug with a potent analgesic activity, but because it is practically insoluble in water, its bioavailability is significantly limited. One of the possible approaches for increasing the solubility and dissolution rate of a drug is to convert it from the crystalline to the amorphous form. Unfortunately, amorphous forms are generally unstable and do not guarantee an appropriate shelf life for the drug product. An interesting possibility for countering this difficulty is to use amorphous polymers to disperse the crystalline drug into the amorphous matrix, thus forming stable amorphous drug dispersions. In the present study, the thermal behavior of nimesulide and its physical stability in the amorphous state were fully characterized, and then, the possibility of prolonging its stability in the amorphous state was evaluated by dispersing the drug into two different amorphous polymers: poly(vinylpyrrolidone) or sodium alginate. The drug–polymer dispersion was obtained by co-heating the mix in a differential scanning calorimetry apparatus. The physicochemical stability of the pure nimesulide and the binary systems was evaluated by the Kolhaush–William–Watts equation. Aging experiments were carried out at different temperatures, and for each one the mean relaxation time constant was calculated to predict the physical stability of the amorphous system. The physical interaction between the drug and the polymer upon heating was determined according to the Gordon–Taylor equation. Our results showed that amorphous nimesulide is fragile, with limited stability, and thus inappropriate for industrial application. The observation that poly(vinylpyrrolidone) strongly increased the mean relaxation time constant of amorphous nimesulide was ascribed to the capacity of the binary system to form hydrogen bonds that stabilize the system. On the contrary, the sodium alginate was unable to increase the stability of the amorphous system and the mean relaxation time constant was even inferior to that of pure nimesulide. The failure of the two compounds to interact can be explained by the sterical hindrance of the sodium alginate chains.

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Acknowledgements

The authors would like to thank Ms. Sheila Beatty for editing the English usage of the manuscript.

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Authors and Affiliations

  1. School of Pharmacy, University of Camerino, Via S. Agostino, 1, 62032, Camerino, Italy

    Roberta Censi, Maria Rosa Gigliobianco & Piera Di Martino

  2. Faculty of Pharmacy, University of Medicine, Tirana, Albania

    Ledjan Malaj

Authors
  1. Roberta Censi
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  2. Maria Rosa Gigliobianco
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  3. Ledjan Malaj
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  4. Piera Di Martino
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Correspondence to Piera Di Martino.

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Censi, R., Gigliobianco, M.R., Malaj, L. et al. Effect of poly(vinylpyrrolidone) or sodium alginate on the stability of the amorphous form of nimesulide. J Therm Anal Calorim 123, 2415–2425 (2016). https://doi.org/10.1007/s10973-015-5175-y

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  • DOI: https://doi.org/10.1007/s10973-015-5175-y

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