EXPERIMENTAL STUDIES ON FORMULATION OF MODIFIED-RELEASE AMIODARONE TABLETS

  • Andreea CRETEANU “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Lacramioara OCHIUZ “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Madalina VIERIU “Grigore T. Popa” University of Medicine and Pharmacy Iasi
  • Gladiola TANTARU “Grigore T. Popa” University of Medicine and Pharmacy Iasi

Abstract

Drug formulations and their technological processes must ensure quality and reproducibility in the conditions of the information transfer between research institutions and industry for the preparation of large amounts of pharmaceutical product. Aim: Analysis of the influence of formulation factors on flow parameters of the powder mixture in order to obtain amiodarone tablets. Material and methods: Data fitting and calculation of statistical indicators for the validation of the experimental plan. The study was carried out using the MODDE 10.1 optimization software. The quantitative variables were amiodarone, amiodarone complex with hydroxypropyl-β-cyclodextrin, Kollidon® SR, Chitosan, Aerosil®, magnesium stearate, and Avicel®, while the qualitative variables were the following flow and compressibility parameters of the mixtures subjected to compression: flow time, coefficient of friction, angle of rest, Hausner index and Carr index. The matrix for optimizing the formulation based on the presented parameters was based on a D-optimal experimental design. Results and Discussion: The results of the study on the influence of formulation factors on flow time confirmed that Kollidon® SR concentration levels decrease the flow time, also confirmed for Chitosan but on a smaller scale. Of the formulation factors, Avicel® and Kollidon® SR variables had the greatest influence on the friction coefficient, increasing the concentration of these parameters generating a decrease in the friction coefficient. Conclusions: The use of experimental designs in the formulation of amiodarone tablets and the formulation analysis based on flow and compressibility parameters allows establishing a hierarchy based on the importance of qualitative variables, influenced by quantitative variables, to identify the optimal formulation and technology for the preparation of tablets.

Author Biographies

Andreea CRETEANU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

Faculty of Pharmacy
Department of Pharmaceutical Sciences II

Lacramioara OCHIUZ, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

Faculty of Pharmacy
Department of Pharmaceutical Sciences II

Madalina VIERIU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

Faculty of Pharmacy
Department of Pharmaceutical Sciences I

Gladiola TANTARU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

Faculty of Pharmacy
Department of Pharmaceutical Sciences I

References

1. Leedy PD, Ormrod JE. Practical Research. Planning and Design, 7th edition New Jersey: Merrill Prentice Hall Inc., 2001.
2. Armstrong NA, James KJ. Pharmaceutical Experimental Design and Interpretation, 2nd edition Lon-don: Taylor & Francis, 1996.
3. De Muth J. Basic Statistics and Pharmaceutical Statistical Applications. New York: Marcel Dekker Inc., 1999.
4. Bolton S, Bon C. Pharmaceutical Statistics-practical and clinical applications, 4th edition Basel: Marcel Dekker Inc., 2004.
5. Popa L. Metodologia cercetării științifice în domeniul farmaceutic. București: Editura Printech, 2003.
6. Păduraru OM, Bosînceanu A, Ţântaru G, Vasile C. Effect of Hydroxypropyl-β-Cyclodextrin on the Solubility of Antiarrytmic Agent. Ing Eng Chem Res 2013; 52: 2174-2181.
7. Bosînceanu A, Popa G, Ţântaru G, Popovici I. Visible spectrophotometric method for amiodarone. Rev Med Chir Soc Med Nat Iasi 2012; 116(1): 330-336.
8. Crețeanu A, Ochiuz L, Vasile C, Paduraru OM, Popescu C, Vieriu M, Panainte AD, Ţântaru G. Thermal Stability Assessment of Amiodarone Hydrochloride in Polymeric Matrix Tablets. Farmacia 2016; 64(6): 940-945.
9. Crețeanu A, Ochiuz L, Vieriu M, Panainte AD, Ţântaru G. In Vitro Dissolution Studies of Amiodarone Hydrochloride from Hydroxy-Propyl-Β-Cyclodextrin/Amiodarone Inclusion Complex Formulated Into Modified-Release Tablets. Med Surg J - Rev Med Chir Soc Med Nat Iasi 2016; 120(3): 715-719.
10. Bosînceanu A, Păduraru OM, Vasile C, Popovici I, Țântaru G, Ochiuz L. Validation of A New Hplc Method Used for Determination of Amiodarone from The Complex with Hydroxypropyl-Beta-Cyclodextrin and from Commercial Tablets. Farmacia 2013; 61(5): 856-864.
11. Bühler V. Polyvinylpyrrolidone excipients for the pharmaceutical industry, 9th revised edition. Lud-wigshafen: BASF SE Pharma Ingredients & Services, 2008.
12. ***Kollidon® SR, a new excipient for smooth direct compression of sustained release dosage forms. Product brochure on Kollidon® SR. Ludwigshafen: BASF, 2000.
13. Kumar MN, Muzzarelli RA, Muzzarelli C, Sashiwa H, Domb AJ. Chitosan chemistry and pharmaceu-tical perspectives. Chem Rev 2004; 104: 6017-6084.
14. ***Dow. Using Dow Excipients for Controlled Release of drugs in Hydrophilic Matrix Systems. Midland: The Dow Chemical Company USA, 2006.
15. Levina M, Rajab-Siahboomi AR. The influence of excipients on drug release from hydroxypropyl methylcellulose matrices. J Pharm Sci 2004; 93(11): 2746-2754.
16. Singh B, Ahuja N. Book review on Pharmaceutical Experimental Design. Int J Pharm 2000; 248: 195-247.
17. Rosner B. Fundamentals of Biostatistics, 6th edition Toronto: Thomson Book Cole, 2006.
18. Schwartz JB, Connor RE. Modern Pharmaceutics. New York: Marcel Dekker Inc., 1999.
19. Petrie A, Sabin C. Medical Statistics at a glance. Massachusetts: Blackwell Science Inc., 2000.
20. Wan Po AL. Statistics for Pharmacists. Berlin: Blackwell Science Ltd., 1998.
Published
2018-12-27