A Statistical Approach to Evaluating the Manufacture of Furosemide Tablets - Pharmaceutical Technology

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A Statistical Approach to Evaluating the Manufacture of Furosemide Tablets
The authors evaluated the manufacturing data of 40-mg tablets of furosemide, a potent diuretic.

Pharmaceutical Technology
Volume 35, Issue 3, pp. 112-121


The statistical approach used in the process evaluation of the blending, tableting, dosage-unit uniformity, weight variation, and dissolution behavior led to better process understanding of the manufacturing process. The results showed that fully nested ANOVA is a powerful tool to identify sources of variability. The process capability indices helped the authors to understand process performance and the potential for process optimization. Although a limited number of batches were investigated, the statistical methods identified possible approaches for process improvement in the manufacturing of furosemide tablets.

Túlia de Souza Botelho is a student, Vanessa Franco Tavares is a student, Cátia Panizzon Dal Curtivo is a student, and Nádia Araci Bou-Chacra* is an assistant professor of pharmaceutics, all at the Faculty of Pharmaceutical Sciences, University of Săo Paulo, 580 Lineu Prestes Ave., Butantan, Săo Paulo, SP – Brazil 05508-900,
. Silvie Rosa Balzan Sarolli is a quality-assurance employee, Márcio Adriano Fernandes is a quality-control employee, and Carmen Maria Donaduzzi is a research pharmacist, all at Prati-Donaduzzi. Raimar Löbenberg is an associate professor of pharmaceutics at the University of Alberta.

*To whom all correspondence should be addressed.

Submitted: Aug. 31, 2010. Accepted: Nov. 29, 2010.


1. L.L.B. Ponto and R.D. Schoenwald, Clin. Pharmacokinet. 18 (1), 460–471 (1990).

2. EMEA, Note for Guidance on Process Validation (London, Mar. 2001), http://www.ema.europa.eu/pdfs/human/qwp/084896en.pdf, accessed Dec. 4, 2009.

3. PIC/S, Validation Master Plan Installation and Operational Qualification Non-Sterile Process Validation Cleaning Validation, (Geneva, Sept. 2007), http://www.picscheme.org/publication.php, accessed Dec. 4, 2009.

4. ANVISA, National Health Surveillance Agency, Resolution-RDC 17 Current Good Manufacturing Practices for Drugs (Brasília,, DF, 2010), ftp://ftp.saude.sp.gov.br/ftpsessp/bibliote/informe_eletronico/2010/iels.abr.10/Iels73/U_RS-MS-ANVISA-RDC-17_160410.pdf, accessed. Aug. 31, 2010.

5. FDA, Guidance for Industry: Process Validation: General Principles and Practices: Draft Guidance (Rockville, MD, Nov. 2008).

6. D. Montgomery, Introduction to Statistical Quality Control (John Wiley and Sons, New York, 5th ed. 2004), p. 776.

7. FDA, Pharmaceutical cGMP for the 21st Century: A Risk Based Approach.

8. ICH, Q9: Quality Risk Management (Geneva, 2006).

9. ICH, Q10: Pharmaceutical Quality System (Geneva, 2007).

10. ICH, Q8(R1): Pharmaceutical Development (Geneva, 2008).

11. Brazilian Pharmacopoeia, 4th ed. (Brazilian Pharmacopoeia, Săo Paulo, 2001), p. 152.1

12. USP 32–NF 27 (US Pharmacopeial Convention, Rockville, MD, 2009), p. 2085.

13. G.E.P. Box and D.R. Cox, J. R. Stat. Soc. Series B Stat. Methodol. 26 (2), 211–252 (1964).

14. A. Czarski, Arch. Mater. Sci. Eng. 34 (1), 39–42 (2008).

15. P. Noceti, J. Smith, and S. Hodges, J. Forecast. 22 (6), 447–455 (2003).

16. H.C. Lin and G.J. Sheen, Qual. Eng. 17 (1), 371–390 (2005).

17. T. Pyzdek and P.A. Keller, The Six Sigma Handbook: A Complete Guide for Green Belts, Black Belts, and Managers at All Levels, (McGraw-Hill, New York, 3rd ed., 2009).

18. A.L.A. Vissotto et al., Pharm. Ind. 70 (11), 1414–1421 (2008).

19. S.S. Pal, Qual. Eng. 17 (1), 77–85 (2005).


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