Calzadilla AW, Moreno MS, García PO, Besada ME, Suárez PY

Language: Spanish
References: 10
Page: 562-572
PDF size: 219.33 Kb.

ABSTRACT

Introduction: "Roberto Escudero Diaz" drug producing company is carrying out the reformulation of 2 % miconazole nitrate cream due to non-compliance with some quality specifications and the microbiological contamination of several industrial batches, so it was required to make major changes in the registered formulation composition.
Objective: to determine the stability of the new 2 % miconazol nitrate cream formulation to verify its validity period.
Methods: the studies followed the regulations in force. Three pilot-scaled batches, packed in 25 g aluminum tubes, were used. The analytical methods were high resolution liquid chromatography technique and thin layer chromatography, being both methods previously validated for these purposes. The selected storage temperatures were 30 ± 2 °C (shelf life) and 40 ± 2 ºC (accelerated stability). The estimated parameters included organoleptic properties, pH, extensibility area, titration, content of related substances and/or degradation products in addition to evaluating the quality of formulation from the microbiological viewpoint.
Results: from the chemical viewpoint, the evaluated batches showed contents over 98 % of analyte and very low levels of related substances, regardless of batch and the storage temperature. The thin layer chromatography did not detect any additional stain attributed to possible degradation products. The extensibility showed normal decrease resulting from progressive structuring of the system and the pH also lowered within the set limits. The microbiological stability of the drug was proved to be high after 12 months.
Conclusions: the cream was chemically, physically and microbiologically stable at room temperature for 12 months, so this is the term suggested as the temporary validity period.

REFERENCES

1. Brunton L. Goodman & Gilman's The Pharmacological Basis of Therapeutics. Section VII Chemotherapy of Microbial Diseases. Antifungal Agents. 12th ed. Connecticut, New Heaven: University Yale; 2011.

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

3. Gómez M, López M. García G. Diseño de una formulación antimicótica. Rev Cubana Farm. 1998 [citado 13 feb 2012];32(1). Disponible en: http://www.bvs.sld.cu/revistas/far/vol32_1_98/far02198.htm

4. Empresa Laboratorio "Roberto Escudero Díaz". No. Reg.: 1168. Información administrativa Miconazol Crema. Parte I. Solicitud de Inscripción Registro de Medicamentos. La Habana, Cuba: Empresa Laboratorio "Roberto Escudero Díaz"; 1988.

5. Regulación 23-2000. Anexo 2. Centro para el Control Estatal de la Calidad de los Medicamentos, Equipos y Dispositivos Médicos. Requerimientos para los estudios de estabilidad para el registro de productos farmacéuticos nuevos y conocidos. La Habana, Cuba: CECMED; 2000.

6. ICH Q1A (R2). Harmonised Tripartite Guideline. Stability Testing of new drug substances and products (Stress Testing). 2003. [cited 2012 Feb 13]. Available from: http://www.ich.org/products/guidelines/quality/quality-single/article/stability-testingof- new-drug-substances-and-products.html

7. García O, Calzadilla W, Rodríguez W, Besada ER, Suárez Y. Evaluación de métodos cromatográficos para la estabilidad química del Nitrato de Miconazol en una nueva crema. Rev Cubana Farm. 2013 [citado 13 feb 2012];47(3). Disponible en: http://scielo.sld.cu/scielo.php?pid=S0034- 75152013000300003&script=sci_arttext

8. ESP-ACC 11-1-064. Especificaciones de calidad del Miconazol crema. Producto Terminado. La Habana, Cuba: Empresa Laboratorio "Roberto Escudero Díaz". 2011.

9. The United Stated Pharmacopoeia 35 and National Formulary 30 (USP 35-NF 30). Validation of compendial procedures. 35 ed. Rockville: Mack Printing; 2011. p. 840.

10. Zumbado H. Análisis Instrumental de Alimentos. Apuntes para un libro de texto. La Habana: Instituto de Farmacia y Alimentos, Universidad de La Habana; 2011. p. 188-90.