Use of Box–Behnken design for optimization of compounded medication: acyclovir capsules report

Authors

  • Suelen da Silva Reis Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia - Universidade Federal Fluminense image/svg+xml
  • Valdemir da Silva Quintanilha Junior Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia - Universidade Federal Fluminense image/svg+xml
  • Gabriella da Silva Boto Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia - Universidade Federal Fluminense image/svg+xml
  • Thalita Martins da Silva Laboratório Universitário Rodolpho Albino - Universidade Federal Fluminense image/svg+xml
  • Elizabeth Valverde Macedo Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia, Laboratório Universitário Rodolpho Albino - Universidade Federal Fluminense image/svg+xml
  • Carlos Augusto de Freitas Peregrino Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia, Laboratório Universitário Rodolpho Albino - Universidade Federal Fluminense image/svg+xml
  • Samanta Cardozo Mourão Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia - Universidade Federal Fluminense image/svg+xml
  • Emeli Moura de Araújo Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia - Universidade Federal Fluminense image/svg+xml

DOI:

https://doi.org/10.22456/2527-2616.113283

Keywords:

Acyclovir, Dissolution, Excipients, Design of experiment, Capsules

Abstract

Campus compounding pharmacies play an important role in public health. Herpes simplex is one of the most common viral diseases in humans, which generates a great demand for acyclovir capsules in compounding pharmacy. It is well known that the formulation's components influence the effectiveness of the drug. The objective of this study is to show the applicability of Box-Behnken design in optimization of a compounded formulation and to evaluate the effect of excipients on dissolution and drug content in acyclovir 200 mg capsules produced at UFF´s University Pharmacy (FAU). The formulations were prepared and evaluated for average weight test, uniformity of dosage units and in vitro dissolution, while meeting pharmacopoeial specifications. A statistical analysis showed that sodium starch glycolate, Aerosil®, influences drug content and dissolution results. Magnesium stearate shows no influence on the dissolution at different concentrations but influences the assay results. A numerical optimization was applied to adjust the formulation variables based on the foresaid responses, accomplishing the best formulation that will be prepared and dispensed at FAU upon medical prescription.

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References

Agência Nacional de Vigilância Sanitária (Anvisa). Resolução RDC n° 67 de 08 de outubro de 2007. Dispõe sobre Boas Práticas de Manipulação de Preparações Magistrais e Oficinais para Uso Humano em farmácias DOU. Brasília, Brazil: Diário Oficial da União; 2007. Available at: http://antigo.anvisa.gov.br/documents/10181/271837 6/RDC_67_2007_COMP.pdf/5de28862-e018-4287- 892e-a2add589ac26. Accessed Mar 29, 2021.

Almeida MLC, Filho APN. Análise das cápsulas manipuladas segundo a RDC 67/2007 para a garantia da qualidade. Rev. Bras. de Farm. 2010; 91(3): 119- 25.

Alalaiwe A, Fayed MH, Alshahrani SM, Alsulays BB, Alshetaili AS, Tawfeek HM, et al. Application of design of experiment approach for investigating the effect of partially pre-gelatinized starch on critical quality attributes of rapid orally disintegrating tablets. J Drug Deliv Sci Technol. 2019; 49: 227-234. ISSN 1773-2247. https://doi.org/10.1016/j.jddst.2018.11.018.

Kharia AA, Singhai AK. Development and optimisation of mucoadhesive nanoparticles of acyclovir using design of experiments approach. J Microencapsul. 2015; 32(6):521-32. doi: 10.3109/02652048.2015.1010457. Epub 2015 Aug 18. PMID: 26333938.

Maniya NH, Patel SR, Murthy ZVP. Development and in vitro evaluation of acyclovir delivery system using nanostructured porous silicon carriers. Chem. Eng. Res. Des. 2015; 104: 551-557, ISSN 0263-8762. https://doi.org/10.1016/j.cherd.2015.09.008

Hassan H, Adam SK, Othman F, Shamsuddin AF, Basir R. Antiviral. Nanodelivery Systems: Current Trends in Acyclovir Administration. J. Nanomater. 2016; 1-8. https://doi.org/10.1155/2016/4591634

Al-Subaie MM, Hosny KM, El-Say KM, Ahmed TA, Aljaeid BM. Utilization of nanotechnology to enhance percutaneous absorption of acyclovir in the treatment of herpes simplex viral infections. Int J Nanomedicine. 2015; 10:3973-85. doi: 10.2147/IJN.S83962.

Stulzer HK, Tagliari MP, Silva MAS, Laranjeira MCM. Desenvolvimento, avaliação e caracterização fisicoquímica de micropartículas constituídas de aciclovir/quitosana desenvolvidas pela técnica de spraydrying. Lat Am J Pharm. 2007; 26(6): 866-71. Available from: http://www.latamjpharm.org/Subscription required.

Rowe, R. C., Sheskey, P. J., & Weller, P. J. (2003). Handbook of pharmaceutical excipients. London: Pharmaceutical Press.

Pinheiro GM, Benavide VG, Volpato NM, Cabral LM, Santos EP. Indicadores para controle de processo na manipulação de cápsulas em farmácia. Rev. Bras. Farm. 2008; 89(1):28-31. http://www.rbfarma.org.br/files/pag_28a31_indicadore s_capsulas.pdf

Brasil. Ministério da Saúde. Agência Nacional de Vigilância Sanitária. Farmacopéia Brasileira, 6ª edição. v. 1. Brasília: Agência Nacional de Vigilância Sanitária, 2019. http://portal.anvisa.gov.br/farmacopeia-brasileira

Brasil. Ministério da Saúde. Agência Nacional de Vigilância Sanitária. Farmacopéia Brasileira, 6ª edição. v. 2. Brasília: Agência Nacional de Vigilância Sanitária, 2019. Disponível em < http://portal.anvisa.gov.br/farmacopeia-brasileira

United States Pharmacopeia. USP 44. Rockville: The United States Pharmacopoeial Convention, 2021.

Soroush H, Ghorbani-Bidkorbeh F, Mortazavi SA, Mehramizi A. Formulation Optimization and Assessment of Dexamethasone Orally Disintegrating Tablets Using Box-Behnken Design. Iran J Pharm Res. 2018; 17(4):1150-1163. PMID: 30568675; PMCID: PMC6269575.

Consiglieri VO, Mourão S, Sampaio M, Granizo P, Garcia P, Martinello V, et al. Improvement of fluconazole flowability and its effect on dissolution from tablets and capsules. Braz. J. Pharm. Sci. 2010; 46(1):115-120. http://www.scielo.br/scielo.php?script=sci_arttext&pid =S1984- 82502010000100013&lng=en. https://doi.org/10.1590/ S1984-82502010000100013.

Dayal P, Pillay V, Babu RJ, Singh M. Box-Behnken experimental design in the development of a nasal drug delivery system of model drug hydroxyurea: characterization of viscosity, in vitro drug release, droplet size, and dynamic surface tension. AAPS PharmSciTech. 2005; 6(4):E573-85. doi: 10.1208/pt060472. PMID: 16408859; PMCID: PMC2750605.

Abbas G, Hanif M, Rasul A, Khan SM, Amir MN, Nasir B, et al. Box-behnken design: a statistical approach to evaluate the effect of crosslinked carboxymethyl cellulose and sodium starch glycolate on release kinetics of drug. Acta Pol. Pharm. 2018; 75(4):965-975.DOI: 10.32383/appdr/79424

Roy H, Rahaman A. Box-Behnken Design for Optimization of Formulation Variables for Fast Dissolving Tablet of Urapidil. Asian J. Pharm. 2018; 12(3):S946. DOI: 10.22377/ajp.v12i03.2632

Masuda T, Yoshihashi Y, Yonemochi E, Fujii K, Uekusa H, Terada K. Cocrystallization and amorphization induced by drug-excipient interaction improves the physical properties of acyclovir. Int J Pharm. 2012; 422(1-2):160-9. doi: 10.1016/j.ijpharm.2011.10.046. Epub 2011 Nov 3. PMID: 22079714.

Vaithianathan S, Haidar SH, Zhang X, Jiang W, Avon C, Dowling TC, et al. Effect of Common Excipients on the Oral Drug Absorption of Biopharmaceutics Classification System Class 3 Drugs Cimetidine and Acyclovir. J Pharm Sci. 2016; 105(2):996-1005. https://doi.org/10.1002/jps.24643

Ansel HC, Allen Jr. LV, Popovich NG editors. Formas Farmacêuticas e Sistemas de Liberação de Fármacos. 8th ed. Porto Alegre: Artmed, 2007.

Scheshowitsch K, Pereira A, Cruz A, Silva MAS, Stulzer HK. Avaliação da Qualidade e Perfil de Dissolução de Capsulas Manipuladas de Piroxicam. Lat. Am. J. Pharm. 2007; 26(5): 645-51. Available from: http://www.latamjpharm.org/Subscription required

Baracat MM, Montanher CLS, Kubacki AC, Martinez RM, Zonta GAN, Duarte JC, Nery MMF, Gianotto EAS, Georgetti SR, Casagrande R. Avaliação da Qualidade de Formulações Manipuladas e Industrializadas de Sinvastatina. Lat. Am. J. Pharm. 2009; 28(3): 427-32. http://www.latamjpharm.org/trabajos/28/3/LAJOP_2 8_3_1_15_52H4GUF7PZ.pdf

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Published

30-06-2021 — Updated on 19-03-2026

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How to Cite

Reis, S. da S., Quintanilha Junior, V. da S., Boto, G. da S., da Silva, T. M., Macedo, E. V., Peregrino, C. A. de F., … de Araújo, E. M. (2026). Use of Box–Behnken design for optimization of compounded medication: acyclovir capsules report. Drug Analytical Research, 5(1), 59–67. https://doi.org/10.22456/2527-2616.113283 (Original work published June 30, 2021)

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ORIGINAL ARTICLES