García PO, Calzadilla AW, Rodríguez BW, Besada MER, Suárez PY

Language: Spanish
References: 12
Page: 300-314
PDF size: 381.02 Kb.

ABSTRACT

Objective: to assess the chromatographic methods for the chemical stability of a new 2 % miconazol nitrate cream.
Methods: various degradation conditions were firstly used in the raw material miconazole nitrate in order to obtain the possible degradation products of this drug and to evaluate them by thin layer chromatography-based method, which was validated to identify the degradation products in the new cream. The performance of the official method based on high resolution liquid chromatography and reported in British Pharmacopeia 2010 was evaluated, and its selectivity against the possible degradation products were also analyzed. Both chromatographic methods were applied to the analysis of cream samples from the three pilot batches under heat stress for 30 days.
Results: the two methods showed high selectivity against excipients and degradation products of the drug. Miconazol nitrate was degraded against acid hydrolysis, thermolysis and photolysis, being the detection limit of 1 µg for the thin layer chromatography. No degradation of the analyte was observed in any of the three analyzed batches according to the qualitative and quantitative results.
Conclusions: these methods are valid for the submitted objective, so they may be used in the chemical stability study of 2 % miconazol nitrate creams.

REFERENCES

1. Mediavilla A, Flórez J. Fármacos antifúngicos. Farmacología humana. 3ra. ed. Barcelona: Masson, SA; 1997. p. 118.

2. Rodríguez W. Reformulación de la crema de nitrato de miconazol al 2 % [tesis]. La Habana: Instituto de Farmacia y Alimentos. Universidad de La Habana; 2012.

3. Centro para el Control Estatal de la Calidad de los Medicamentos. Regulación 41. Validación de métodos analíticos. La Habana: CECMED; 2007.

4. Castiñeira M, González HM. Control de Medicamentos 2da. ed. La Habana: Félix Varela; 2002. p. 23.

5. Ros JW, Van der Meer YG. Preparation of Miconazole Oral Gel. Pharm Weekbl. 1990;125:70-1.

6. Ashour S, Kattan N. Determinación simultánea de nitrato de miconazol y metronidazol en diferentes formas farmacéuticas por cromatografía de gases y detector de ionización de llama (GC-FID). Rev Intern de Cienc Bioméd. 2010;6(1):13-8.

7. The United Stated Pharmacopoeia 33 and National Formulary 28 (USP33-NF28). Validation of compendial procedures. 33 ed. Rockville: Mack Printing; 2010.

8. British Pharmacopoeia. Volume I & II. Monographs: Medicinal and Pharmaceutical Substances-Miconazole Nitrate. London: The Stationery Office; 2010. Versión electrónica 14.0.

9. O'Connor N; Geary, M. The Determination of Miconazole and its Related Production Impurities Together with Basic Solution Stability Studies Using a Sub 2 μm Chromatographic Column. J Cromatogr Sci. 2012;50(3):199-205.

10. ICH Q1A (R2). Harmonised Tripartite Guideline. Stability Testing of new drug substances and products (Stress Testing). Geneva: ICH; 2003.

11. ICH Q1B. Harmonised Tripartite Guideline. Photostability Testing of New Drug Substances and Products. Geneva: ICH; 1996.

12. Centro para el Control Estatal de la Calidad de los Medicamentos. Regulación 23: Requerimientos para los estudios de estabilidad para el registro de productos farmacéuticos nuevos y conocidos. La Habana: CECMED; 2000.