Statistical process control of manufacturing tablets for antiretroviral therapy

Authors

  • Nataly Paredes da Rocha Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
  • Osvaldo Cirilo da Silva Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
  • Eduardo José Barbosa Universidade de São Paulo. Faculdade de Ciências Farmacêuticas https://orcid.org/0000-0003-3892-2193
  • Gidel Soares Fundação para o Remédio Popular “Chopin Tavares de Lima" (FURP), São Paulo, Brazil
  • Roberto Oliveira Fundação para o Remédio Popular “Chopin Tavares de Lima" (FURP), São Paulo, Brazil
  • Lis Marie Monteiro Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
  • Nádia Araci Bou-Chacra Universidade de São Paulo. Faculdade de Ciências Farmacêuticas

DOI:

https://doi.org/10.1590/s2175-97902023e22099%20%20

Keywords:

Capability indices, Control charts, HIV treatment, Manufacturing process, Quality tools

Abstract

In this study, the manufacturing process of lamivudine (3TC) and zidovudine (AZT) tablets (150+300 mg respectively) was evaluated using statistical process control (SPC) tools. These medicines are manufactured by the Fundação para o Remédio Popular “Chopin Tavares de Lima” (FURP) laboratory, and are distributed free of charge to patients infected with HIV by the Ministry of Health DST/AIDS national program. Data of 529 batches manufactured from 2012 to 2015 were collected. The critical quality attributes of weight variation, uniformity of dosage units, and dissolution were evaluated. Process stability was assessed using control charts, and the capability indices Cp, Cpk, Pp, and Ppk (process capability; process capability adjusted for non-centered distribution; potential or global capability of the process; and potential process capability adjusted for non-centered distribution, respectively) were evaluated. 3TC dissolution data from 2013 revealed a non-centered process and lack of consistency compared to the other years, showing Cpk and Ppk lower than 1.0 and the chance of failure of 2,483 in 1,000,000 tablets. Dissolution data from 2015 showed process improvement, revealed by Cpk and Ppk equal to 2.19 and 1.99, respectively. Overall, the control charts and capability indices showed the variability of the process and special causes. Additionally, it was possible to point out the opportunities for process changes, which are fundamental for understanding and supporting a continuous improvement environment.

Downloads

Download data is not yet available.

References

Anderson PL, Rower JE. Zidovudine and Lamivudine for HIV Infection. Clin Med Rev Ther 2010;2:115-27.

Anderson TW, Darling DA. A Test of Goodness of Fit. J Am Stat Assoc 1954;49(268):765-9.

ANVISA. Métodos Gerais. In: Farmacopeia Brasileira 5th ed. São Paulo; 2010.

Brasil. Boletim Epidemiológico HIV/Aids | 2019. Boletim Epidemiológico HIV/AIDS 2019. Available from: http://www.aids.gov.br/pt-br/pub/2019/boletim-epidemiologico-de-hivaids-2019

» http://www.aids.gov.br/pt-br/pub/2019/boletim-epidemiologico-de-hivaids-2019

Brasil. Tratamento para o HIV | Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis Ministério Da Saúde. 2019. Available from: http://www.aids.gov.br/pt-br/publico-geral/o-que-e-hiv/tratamento-para-o-hiv

» http://www.aids.gov.br/pt-br/publico-geral/o-que-e-hiv/tratamento-para-o-hiv

Boyles RA. The Taguchi Capability Index. J Qual Technol 1991;23(1):17-26.

Chatterjee M, Chakraborty AK. Some process capability indices for unilateral specification limits-Their properties and the process capability control charts. Commun Stat - Theory Methods 2016;45(24):7130-60.

Chopra V, Bairagi M, Trivedi P, Nagar M. A case study: Application of statistical process control tool for determining process capability and sigma level. PDA J Pharm Sci Technol 2012;66(2):98-115.

Crowley ME. A study of microcrystalline cellulose variability and how this impacts compaction performance University College Cork; 2018.

Dal Curtivo CP, Funghi NB, Tavares GD, Barbosa SF, Löbenberg R, Bou-Chacra NA. The critical role of NIR spectroscopy and statistical process control (SPC) strategy towards captopril tablets (25 mg) manufacturing process understanding: A case study. Pharm Dev Technol 2015;20(3):345-51.

de Souza Botelho T, Tavares VF, Dal Curtivo CP, Sarolli SRB, Fernandes MA, Donaduzzi CM, et al. A Statistical approach to: Evaluating the manufacture of furosemide tablets. Pharm Technol 2011;35(3):112-21.

Dudek-Burlikowska M. Quality estimation of process with usage control charts type X-R and quality capability of process Cp, Cpk. J Mater Process Technol 2005;162-163:736-43.

FDA. Guidance for Industry - Process Validation: General Principles and Practices Current Good Manufacturing Practices (CGMP). 2011. p. 1-19. Available from: https://www.fda.gov/downloads/drugs/guidances/ucm070336.pdf

» https://www.fda.gov/downloads/drugs/guidances/ucm070336.pdf

FDA. Pharmaceutical Quality System Elements: Product Quality Management 2011. Available from: https://www.fda.gov/files/drugs/published/Product-Quality-Management.pdf

» https://www.fda.gov/files/drugs/published/Product-Quality-Management.pdf

Fauchet F, Treluyer JM, Frange P, Urien S, Foissac F, Bouazza N, et al. Population pharmacokinetics study of recommended zidovudine doses in HIV-1-infected children. Antimicrob Agents Chemother 2013;57(10):4801-8.

Flynn PM, Rodman J, Lindsey JC, Robbins B, Capparelli E, Knapp KM, et al. Intracellular pharmacokinetics of once versus twice daily zidovudine and lamivudine in adolescents. Antimicrob Agents Chemother . 2007;51(10):3516-22.

Guideline ICH. Pharmaceutical Quality System Q10 2008. p. 1-17. Available from: https://database.ich.org/sites/default/files/Q10 Guideline.pdf

» https://database.ich.org/sites/default/files/Q10 Guideline.pdf

Kashif M, Aslam M, Rao GS, Al-Marshadi AH, Jun CH. Bootstrap Confidence intervals of the modified process capability index for weibull distribution. Arab J Sci Eng 2017;42(11):4565-73.

Kirsch D. Fixing tableting problems. Pharm Technol . 2015;39(5):58-9.

Kotz S, Johnson NL. Process capability indices - A review, 1992-2000. J Qual Technol . 2002;34(1):2-19.

Kovářík M, Sarga L. Process capability indices for non-normal data. WSEAS Trans Bus Econ 2014;11:419-29.

Montgomery DC. Introdução ao controle estatístico da qualidade Vol. 7. Rio de Janeiro; 2015.

Nishiyama T, Ogata T, Ozeki T. Preparation of bitter taste-masking granules of lafutidine for orally disintegrating tablets using water-insoluble/soluble polymer combinations. J Drug Deliv Sci Technol 2016;32:38-42. Available from: http://dx.doi.org/10.1016/j.jddst.2016.01.005

» http://dx.doi.org/10.1016/j.jddst.2016.01.005

Pereira P. Process capability indexes: Trends and developments in the manufacturing of blood components. Transfus Apheresis Sci 2021;60(6):103314. Available from: https://doi.org/10.1016/j.transci.2021.103314

» https://doi.org/10.1016/j.transci.2021.103314

Samohyl RW. Controle estatístico de processo e ferramentas da qualidade. In: M.M. Carvalho, E.P. Paladin and E.P. Paladini, Eds E, editor. Gestão da qualidade: teoria e casos Rio de Janeiro: Elsevier. 2009:261-300.

Shah S, Shridhar P, Gohil D. Control chart : A statistical process control tool in pharmacy. Asian J Pharm 2010;4(3):184-92.

Schiffman SS, Zervakis J, Shaio E, Heald AE. Effect of the nucleoside analogs zidovudine, didanosine, stavudine, and lamivudine on the sense of taste. Nutrition 1999;15(11-12):854-9.

WHO. Number of new HIV infections Estimates by WHO region 2019. Available from: https://apps.who.int/gho/data/node.main.HIVINCIDENCE

» https://apps.who.int/gho/data/node.main.HIVINCIDENCE

Yap BW, Sim CH. Comparisons of various types of normality tests. J Stat Comput Simul 2011;81(12):2141-55.

Downloads

Published

2023-06-13

Issue

Section

Original Article

How to Cite

Statistical process control of manufacturing tablets for antiretroviral therapy. (2023). Brazilian Journal of Pharmaceutical Sciences, 59, e22099. https://doi.org/10.1590/s2175-97902023e22099