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Influence of Process and Formulation Parameters on Dissolution and Stability Characteristics of Kollidon® VA 64 Hot-Melt Extrudates

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Abstract

The objective of the present study was to investigate the effects of processing variables and formulation factors on the characteristics of hot-melt extrudates containing a copolymer (Kollidon® VA 64). Nifedipine was used as a model drug in all of the extrudates. Differential scanning calorimetry (DSC) was utilized on the physical mixtures and melts of varying drug–polymer concentrations to study their miscibility. The drug–polymer binary mixtures were studied for powder flow, drug release, and physical and chemical stabilities. The effects of moisture absorption on the content uniformity of the extrudates were also studied. Processing the materials at lower barrel temperatures (115–135°C) and higher screw speeds (50–100 rpm) exhibited higher post-processing drug content (~99–100%). DSC and X-ray diffraction studies confirmed that melt extrusion of drug–polymer mixtures led to the formation of solid dispersions. Interestingly, the extrusion process also enhanced the powder flow characteristics, which occurred irrespective of the drug load (up to 40% w/w). Moreover, the content uniformity of the extrudates, unlike the physical mixtures, was not sensitive to the amount of moisture absorbed. The extrusion conditions did not influence drug release from the extrudates; however, release was greatly affected by the drug loading. Additionally, the drug release from the physical mixture of nifedipine–Kollidon® VA 64 was significantly different when compared to the corresponding extrudates (f 2 = 36.70). The extrudates exhibited both physical and chemical stabilities throughout the period of study. Overall, hot-melt extrusion technology in combination with Kollidon® VA 64 produced extrudates capable of higher drug loading, with enhanced flow characteristics, and excellent stability.

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ACKNOWLEDGMENTS

This project was supported by Grant No. P20RR021929 from the National Center for Research Resources (NIH/NCRR). The authors would also like to thank BASF Corporation for its generous supply of Kollidon®VA 64, as well as Dr. James W. McGinity for his assistance in conducting XRD studies.

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Authors and Affiliations

  1. Nektar Therapeutics, 455 Mission Bay Blvd S, San Francisco, California, 94158, USA

    Sindhuri Maddineni

  2. Mallinckrodt, Pharmaceutical R&D, 385 Marshall Ave, Webster Groves, Missouri, 63021, USA

    Sunil Kumar Battu

  3. Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA

    Joe Morott, Soumyajit Majumdar, S. N. Murthy & Michael A. Repka

  4. Department of Pharmaceutics, School of Pharmacy, and Pii Center for Pharmaceutical Technology, The University of Mississippi, University, Mississippi, 38677, USA

    Soumyajit Majumdar & Michael A. Repka

Authors
  1. Sindhuri Maddineni
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  2. Sunil Kumar Battu
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  3. Joe Morott
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  4. Soumyajit Majumdar
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  5. S. N. Murthy
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  6. Michael A. Repka
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Correspondence to Sunil Kumar Battu.

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Maddineni, S., Battu, S.K., Morott, J. et al. Influence of Process and Formulation Parameters on Dissolution and Stability Characteristics of Kollidon® VA 64 Hot-Melt Extrudates. AAPS PharmSciTech 16, 444–454 (2015). https://doi.org/10.1208/s12249-014-0226-4

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  • DOI: https://doi.org/10.1208/s12249-014-0226-4

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