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The Improvement of the Dissolution Rate of Ziprasidone Free Base from Solid Oral Formulations

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Abstract

This work aims at increasing solubility and dissolution rate of ziprasidone free base—Biopharmaceutics Classifaction System (BCS) class II compound. The authors describe a practical approach to amorphization and highlight problems that may occur during the development of formulations containing amorphous ziprasidone, which was obtained by grinding in high-energy planetary ball mills or cryogenic mills. The release of ziprasidone free base from the developed formulations was compared to the reference drug product containing crystalline ziprasidone hydrochloride—Zeldox® hard gelatin capsules. All preparations were investigated using compendial tests (USP apparatuses II and IV) as well as novel, biorelevant dissolution tests. The novel test methods simulate additional elements of mechanical and hydrodynamic stresses, which have an impact on solid oral dosage forms, especially during gastric emptying. This step may prove to be particularly important for many formulations of BCS class II drugs that are often characterized by narrow absorption window, such as ziprasidone. The dissolution rate of the developed ziprasidone free base preparations was found to be comparable or even higher than in the case of the reference formulation containing ziprasidone hydrochloride, whose water solubility is about 400 times higher than its free base.

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ACKNOWLEDGMENTS

Karolina Adrjanowicz acknowledges financial assistance from the National Centre for Research and Development (Nanomaterials and their potential application in nanobiomedicine).

Kaminska Ewa is thankful for the financial support from the National Center of Science based on decision DEC-2013/09/D/NZ7/04194

Grzegorz Garbacz would like to thank the German Federal Ministry of Education and Research for the financial support (BMBF FKZ 03IPT612C).

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Authors and Affiliations

  1. Pharmaceutical Works Polpharma SA, Pelplinska 19, 83-200, Starogard Gdanski, Poland

    Daniel Zakowiecki & Lech Swinder

  2. Department of Pharmaceutical Technology, Medical University of Gdansk, Hallera 107, 80-416, Gdansk, Poland

    Krzysztof Cal

  3. Institute of Physics, University of Silesia, Uniwersytecka 4, 40-007, Katowice, Poland

    Kamil Kaminski

  4. NanoBioMedical Centre, Adam Mickiewicz University, Umultowska 85, 61-614, Poznan, Poland

    Karolina Adrjanowicz

  5. Department of Pharmacognosy and Phytochemistry, Medical University of Silesia in Katowice, ul. Jagiellonska 4, 41-200, Sosnowiec, Poland

    Ewa Kaminska

  6. Institute of Pharmacy, University of Greifswald, Felix-Hausdorf-Strasse 3a, 17489, Greifswald, Germany

    Grzegorz Garbacz

  7. Physiolution GmbH, Walther-Rathenau-Strasse 49 a, 17489, Greifswald, Germany

    Grzegorz Garbacz

Authors
  1. Daniel Zakowiecki
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  2. Krzysztof Cal
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  3. Kamil Kaminski
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  4. Karolina Adrjanowicz
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  6. Ewa Kaminska
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  7. Grzegorz Garbacz
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Correspondence to Daniel Zakowiecki.

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Zakowiecki, D., Cal, K., Kaminski, K. et al. The Improvement of the Dissolution Rate of Ziprasidone Free Base from Solid Oral Formulations. AAPS PharmSciTech 16, 922–933 (2015). https://doi.org/10.1208/s12249-015-0285-1

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  • DOI: https://doi.org/10.1208/s12249-015-0285-1

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