Physicochemical stability evaluation of liquid extemporaneous preparation based on tretinoin for administration via enteral tuve

Authors

DOI:

https://doi.org/10.30968/rbfhss.2024.151.0927

Abstract

Objective: The purpose of the study was to evaluate the content and physicochemical stability of a liquid oral formulation obtained from ATRA gelatin capsules in an oil/water vehicle, given the demand for this formulation for intubated patients undergoing treatment for acute promyelocytic leukemia. Methods: Analyzes were performed using High Performance Liquid Chromatography (HPLC) coupled to a UV detector, using a C-18 column. The run was performed with a mobile phase composed of ultrapure water with 0.5% glacial acetic acid (v/v) as solvent A and acetonitrile as solvent B, in an isocratic run (25:75) (A/B) with a flow of 1 mL/min, temperature at 30°C and detection at 355 nm. The sample injection was 10 μL and the run time was 12 min. The oral formulations were prepared from ATRA (Vesanoid, FQM) in mineral oil/ultrapure water (3:7) (v/v) by dissolution process and heating at 40°C, in oral dosers protected from light and kept under refrigeration (2 – 8°C). Analyzes were performed on days 1, 2, 3, 7, 9 and 14. Results: The extemporaneous preparation showed acceptable visual physical stability, with a change in appearance due to the hardening of aqueous phase, corrected by heating the formulation in water bath at 40°C. The ATRA content was considered adequate until D3 according to the Brazilian Pharmacopeia (FB) 6th edition, presenting 103.3%, 94.8% and 95.6%, on days 1, 2 and 3, respectively. The concentration of isotretinoin, a degradation product, varied from 0.16% to 1.44%, between days 1 and 14, respectively. Conclusion: The results suggested that the liquid oral preparation presented satisfactory content and physicochemical stability for up 48 hours after preparation, when stored protected from light and under refrigeration, as recommended by RDC 67/2007.

Downloads

Download data is not yet available.

References

WHO. Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4th edition, Swerdlow SH, Campo E, Harris NL, et al. International Agency for Research on Cancer (IARC), Lyon 2017.

Warrell Jr, RP, de The, H, Wang, ZY, et al. Acute promyelocytic leukemia. New England Journal of Medicine, 1993;329(3):177-189. doi: 10.1056/NEJM199307153290307

de The, H. Differentiation therapy revisited. Nature Reviews Cancer, 2018; 18(2):117-127. doi: 10.1038/nrc.2017.103

Rowe, JM, Tallman, MS. How I treat acute myeloid leukemia. Blood, The Journal of the American Society of Hematology, 2010; 116(17):3147-3156. doi: 10.1182/blood-2010-05-260117

Brunton, LL, Chabner, BA, Knollmann, BC. As bases farmacológicas da terapêutica de Goodman & Gilman, 12ª edição. Porto Alegre: AMGH Editora; 2012.

Pinheiro, RF, Pelloso, LAF, Mihoko, Y, et al. Síndrome Atra: experiencia de 10 anos. Revista Brasileira de Cancerologia, 2003; 49(1):27-31. doi: 10.32635/2176-9745.RBC.2003v49n1.2120

Ministério da Saúde. Agência Nacional de Vigilância Sanitária (ANVISA). Consulta de Medicamentos. Tretinoína. Available in: https://consultas.anvisa.gov.br/#/medicamentos/25351244135201789/?substancia=9162. Accessed on: 23rd Oct 2023.

NIOSH List of antineoplastic and other hazardous drugs in healthcare settings. Atlanta, USA: National Institute of Occupational Safety and Health (NIOSH), Department of Health and Human Services, Center for Disease Control and Prevention; 2020. Available in: https://www.cdc.gov/niosh/docket/review/docket233c/pdfs/DRAFT-NIOSH-Hazardous-Drugs-List-2020.pdf. Accessed on: 12nd Dec 2022.

Przybylski, DJ, Jared, JR, Fallon, MJ. Extemporaneous compounding and administration of tretinoin slurry for acute promyelocytic leukemia. Journal of Oncology Pharmacy Practice, 2021; 27(7):1779-1783. doi: 10.1177/1078155221990091

Okumura, LM, Baruel-Okumura, PC, Veroneze, C. Administration of all-trans retinoic acid through enteral tubes in acute promyelocytic leukemia: the handling of cytotoxic agents and clinical benefits. Revista Brasileira de Hematología e Hemoterapia, 2017; 39(1):86-88. doi: 10.1016/j.bjhh.2016.11.001

Lam, MSH. Extemporaneous compounding of oral liquid dosage formulations and alternative drug delivery methods for anticancer drugs. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2011; 31(2):164-192. doi: 10.1592/phco.31.2.164

Lara, VCD. Desenvolvimento de nanocápsulas contendo ácido retinóico pata tratamento tópico da acne [Dissertação de mestrado]. UFMG, Belo Horizonte, 2008.

UNITED STATES PHARMACOPEIA. Pharmacopeial Forum Volume n°41 – Tretinoin, 2019. Available in: https://online.uspnf.com/uspnf/document/GUID-23BED26C-AC53-40B7-AB07-12B20ECCF72A-3-en-US?highlight=tretinoin. Acessed on: 21st Dec 2021.

Roy, C, Chakrabarty, J. Stability indicating RP-HPLC method development and validation for determination of potential degradation impurities of tretinoin in tretinoin topical pharmaceutical formulation. Der Pharmacia Sinica, 2013; 4(4):6-14. doi: 10.3797/scipharm.1303-22

BRASIL, Agência Nacional de Vigilância Sanitária. Comissão da Farmacopeia Brasileira. Formulário Nacional da Farmacopeia Brasileira. 6ª edição, Volume 2. Brasília, 2019. Available in: https://www.gov.br/anvisa/pt-br/assuntos/farmacopeia/farmacopeia-brasileira/insumos-farmaceuticos-e-especialidades-ate-2a-errata-p-pdf-com-capa.pdf. Accessed on: 23th Oct 2023.

BRASIL, Agência Nacional de Vigilância Sanitária. Resolução RDC n°67, de 8 de outubro de 2007. Dispõe sobre Boas Práticas de Manipulação de Preparações Magistrais e Oficinais para Uso Humano em farmácias. Brasília, 2007. Available in: https://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2007/rdc0067_08_10_2007.html. Accessed on: 20th Nov 2023.

BRASIL, Agência Nacional de Vigilância Sanitária. Resolução n° 01, de 29 de julho de 2005. Guia para realização de estudos de estabilidade. Brasília, 2005. Available in: https://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2005/res0001_29_07_2005. html. Accessed on: 30th Jan 2023.

Diniz, D, Lima, EM, Antoniosi Filho, NR. Isotretinoína: perfis farmacológico, farmacocinético e analítico. Revista Brasileira de Ciências Farmacêuticas, 2002; 38(1):415-430. doi:10.1590/S1516-93322002000400004

Herceglija, EI. Stability testing of all-trans-retinol in an experimental cosmetic formulation and in methanol and methanol containing butylhydroxytoluene (BHT) using reversed-phase HPLC, 2021. Available in: https://www.diva-portal.org/smash/get/diva2:1598594/FULLTEXT01.pdf. Accessed on: 22nd Dec 2022.

British Pharmacopoeia. Medicines & Healthcare products Regulatory Agency. Monographs: Tretinoin. Available in: ile:///D:/BP 2023/bp-2023/Monographs pdfs/tretinoin [webofpharma.com].html. Accessed: 13rd Oct 2023.

UNITED STATES PHARMACOPEIA. General Chapters <795> Pharmaceutical Compounding – Nonsterile Preparations, 2020. Available in: https://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/revisions/gc-795-rb-notice-20200424.pdf. Accessed on: 13rd Feb 2023.

Sahnoune, M., Tokhadze, N, El Kettani, SEC, et al. Drug interactions with plasticized PVCs. ACS Applied Polymer Materials, 2022; 4(6):4538-4550. doi: 10.1021/acsapm.2c00532

Allwood, MC. Drug interactions with plastics and their biological consequences. Biodeterioration 7, 1988; p. 157-162. doi: 10.1007/978-94-009-1363-9-21

National Center for Biotechnology Information. PubChem Compound Summary for CID 444795, Tretinoin. Available in: https://pubchem.ncbi.nlm.nih.gov/compound/Tretinoin. Accessed on: 12th Dec 2022.

Takitani, K, Nakao, Y, Kosaka, Y, et al. Low plasma level of alltrans retinoic acid after feeding tube administration for acute promyelocytic leukemia. American Journal of Hematology, 2004; 76(1):94–95. doi: 10.1002/ajh.2004

Published

2024-03-22

How to Cite

1.
COELHO LM, VEIGA A de A, DE SOUZA LM, DE SOUZA GM, COSTA VH, CARLOTTO J. Physicochemical stability evaluation of liquid extemporaneous preparation based on tretinoin for administration via enteral tuve. Rev Bras Farm Hosp Serv Saude [Internet]. 2024Mar.22 [cited 2024May20];15(1):927. Available from: https://www.rbfhss.org.br/sbrafh/article/view/927

Issue

Section

ORIGINAL ARTICLES