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AAPS PharmSciTech

, Volume 16, Issue 4, pp 922–933 | Cite as

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

  • Daniel Zakowiecki
  • Krzysztof Cal
  • Kamil Kaminski
  • Karolina Adrjanowicz
  • Lech Swinder
  • Ewa Kaminska
  • Grzegorz Garbacz
Research Article

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.

KEY WORDS

amorphization dissolution stress test device enhanced dissolution solubility improvement ziprasidone free base formulations 

Notes

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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Copyright information

© American Association of Pharmaceutical Scientists 2015

Authors and Affiliations

  • Daniel Zakowiecki
    • 1
  • Krzysztof Cal
    • 2
  • Kamil Kaminski
    • 3
  • Karolina Adrjanowicz
    • 4
  • Lech Swinder
    • 1
  • Ewa Kaminska
    • 5
  • Grzegorz Garbacz
    • 6
    • 7
  1. 1.Pharmaceutical Works Polpharma SAStarogard GdanskiPoland
  2. 2.Department of Pharmaceutical TechnologyMedical University of GdanskGdanskPoland
  3. 3.Institute of PhysicsUniversity of SilesiaKatowicePoland
  4. 4.NanoBioMedical CentreAdam Mickiewicz UniversityPoznanPoland
  5. 5.Department of Pharmacognosy and PhytochemistryMedical University of Silesia in KatowiceSosnowiecPoland
  6. 6.Institute of PharmacyUniversity of GreifswaldGreifswaldGermany
  7. 7.Physiolution GmbHGreifswaldGermany

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