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Amorphous Solid Dispersions of Sulfonamide/Soluplus® and Sulfonamide/PVP Prepared by Ball Milling

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Abstract

The aim of this paper is to investigate the physicochemical properties of binary amorphous dispersions of poorly soluble sulfonamide/polymeric excipient prepared by ball milling. The sulfonamides selected were sulfathiazole (STZ), sulfadimidine (SDM), sulfamerazine (SMZ) and sulfadiazine (SDZ). The excipients were polyvinylpyrrolidone (PVP) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer, commercially known as Soluplus®. Co-milled systems were characterised by powder X-ray diffraction and differential scanning calorimetry. PVP was shown to form amorphous dispersions over a wider composition range than Soluplus® for the four sulfonamides tested. Moreover, amorphous dispersions made with PVP were homogeneous [single glass transition (Tg)], while amorphous dispersions made from Soluplus® were heterogeneous (two Tgs). This behaviour is consistent with the fact that all the sulfonamides tested presented a lower solubility in Soluplus® than in PVP, as evidenced by Flory–Huggins parameters determined. Amorphous dispersions of SDM with Soluplus® could be produced even though SDM does not amorphise alone upon milling and Soluplus® presents Tg at a lower temperature than SDM. Amorphous dispersions of SMZ could be prepared with a lower excipient concentration compared to STZ, SDM and SDZ, which may reflect the one-dimensional H-bonding network in SMZ compared to the 2D or 3D H-bonding network found in the other sulfonamides. Stability tests (60% RH/25°C) revealed that dispersions made with Soluplus® remained dry and powdery compared to those made with PVP that formed a sticky paste in less than 2 weeks, indicating a possible advantage of using Soluplus® in terms of increased physical stability under high humidity storage conditions.

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ACKNOWLEDGMENTS

This paper is based upon works supported by the Science Foundation Ireland under grant no. [07/SRC/B1158] as part of the Solid State Pharmaceutical Cluster (SSPC).

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Authors and Affiliations

  1. School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, University of Dublin, Dublin 2, Ireland

    Vincent Caron, Lidia Tajber, Owen I. Corrigan & Anne Marie Healy

  2. School of Chemistry, National University of Ireland, Galway, Galway, Ireland

    Yun Hu, Andrea Erxleben & Patrick McArdle

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  1. Vincent Caron
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  2. Yun Hu
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  3. Lidia Tajber
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  6. Patrick McArdle
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  7. Anne Marie Healy
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Correspondence to Anne Marie Healy.

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Caron, V., Hu, Y., Tajber, L. et al. Amorphous Solid Dispersions of Sulfonamide/Soluplus® and Sulfonamide/PVP Prepared by Ball Milling. AAPS PharmSciTech 14, 464–474 (2013). https://doi.org/10.1208/s12249-013-9931-7

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