Application of Arrhenius Equation and Plackett-Burman Design to Ascorbic Acid Syrup Development

Srisagul Sungthongjeen

Authors

Srisagul Sungthongjeen Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, NaresuanUniversity, Phitsanulok 65000, Thailand.

Keywords:

Arrhenius equation, Plackett-Burman design, Ascorbic acid syrup

Abstract

Stability testing and drug-excipients compatibility of pharmaceutical dosage forms are necessary to perform during the early stages of product development. The aim of this study was to apply Arrhenius equation and Plackett-Burman design for stability testing and drug-excipients compatibility of formulations, respectively. The stability of ascorbic acid in syrup was examined using an accelerated stability testing according to the Arrhenius equation. The formulations were stored at room temperature and over the temperature range of 40-70°C. A linear regression line was obtained from Arrhenius plot of the reaction rate (k) against reciprocal of degree kelvin. The heat of activation was found to be 17.96 kcal/mole. Plackett-Burman experimental design was used to investigate the compatibility of ascorbic acid with various syrup excipients. It was found that glycerin (5%v/v) exerted a significant stabilizing effect on ascorbic acid, whereas sugar cane syrup (33.3%v/v) had destabilizing effect. The other excipients appeared to be no significant effect on ascorbic acid stability. The study demonstrated that Arrhenius equation would be useful for the prediction of product stability and the stabilizing or destabilizing effects of excipients could be identified by Plackett-Burman design.

References

Bandelin, F. J., & Tuschhoff, J. V. (1954). Ascorbic acid syrup. Journal of the American Pharmaceutical Association (Practical Pharmacy

Edition), 15, 761-763.

Bandelin, F. J., & Tuschhoff, J. V. (1955). The stability of ascorbic acid in various liquid media. Journal of the American Pharmaceutical Association (Scientific Edition), 44, 241-244.

Bartilucci, A., & Foss, N. E. (1954). Cyanocobalamin (Vitamin B12): A study of the stability of cyanocobalamin and ascorbic acid in liquid formula tions. Journal of the American Pharmaceutical Association

(Scientific Edition), 43, 159-162.

Behl, C. R., Agarwala, B. P., Giudici, R. A., & Galinsky, A. M. (1976). Improved taste acceptability for an oral hyperalimentation dosage form. American Journal of Hospital Pharmacy, 33, 1014-1017.

Bibart, C. H. (1979). Stability testing for expiration dating. Drug Development and Industrial Pharmacy, 5, 349-363.

Blasco, R., Esteve, M. J., Frígola, A., & Rodrigo, M. (2004). Ascorbic acid degradation kinetics in mushrooms in a high-temperature short-time process controlled by a thermoresistometer. Lebensmittel-Wissenschaft und –Technologie, 37, 171-175.

Blaug, S. M., & Hajratwala, B. (1972). Kinetics of aerobic oxidation of ascorbic acid. Journal of Pharmaceutical Sciences, 61, 556-562.

Carstensen, J. T. (2000). Solution Kinetics. In J. T. Carstensen, & C. T. Rhodes (Eds.), Drug Stability: Principles and Practices (3rd ed., pp.19-55). New York: Marcel Dekker.

Connors, K. A., Amidon, G. L., & Stella, V. J. (1986). Chemical stability of pharmaceuticals: A handbook for pharmacists (2nd ed.). New York: Wiley-Interscience Publication.

Dürig, T., & Fassihi, A. R. (1993). Identification of stabilizing and destabilizing effects of excipient-drug interactions in solid dosage form design. International Journal of Pharmaceutics, 97, 161-170.

Ertel, K. D., & Carstensen, J. T. (1990). Examination of a modified Arrhenius relationship for pharmaceutical stability prediction. International Journal of Pharmaceutics, 61, 9-14.

Esteve, M. J., Frígola, A., Martorell, L., & Rodrigo, M. C. (1998). Kinetics of ascorbic acid degradation in green asparagus during heat processing. Journal o f Food Protection, 61, 1518-1521.

Finholt, P., Paulssen, R. B., Alsos, I., & Higuchi, T. (1965). Rates studies on the anaerobic degradation of ascorbic acid II: Rate of formation of carbon dioxide. Journal of Pharmaceutical Sciences, 54, 124-128.

Garrett, E. R. (1962). Prediction of stability of drugs and pharmaceutical preparations. Journal of Pharmaceutical Sciences, 51, 811-833.

Garrett, E. R., & Carper, R. F. (1955). Prediction of stability in pharmaceutical preparations I. Color stability in a liquid multisulfa preparation. Journal of the American Pharmaceutical Association (Scientific Edition), 44, 515-518.

Giral, F. (1947). On the stability of vitamin C in aqueous solutions and in pharmaceutical preparations. Journal of the American

Pharmaceutical Association (Scientific Edition), 36, 82-84.

Kibbe, A. H. (2000). Handbook of pharmaceutical excipients (3rd ed.). Washington, DC: American Pharmaceutical Association.

Lachman, L., Lieberman, H. & Kanig, J. L. (1986). The theory and practice of industrial pharmacy (3rd ed.). Philadelphia: Lea & Febiger.

Motola, S., & Agharkar, S. N. (1992). Preformulation research of parenteral medications (2nd ed.). In K. E. Avis, H. A. Lieberman, & L. Lachman (Eds.), Pharmaceutical dosage forms: Parenteral medications (Vol. 1, pp. 115-172). New York: Marcel Dekker.

Plackett, R. L., & Burman, J. P. (1946). The design of optimum multifactorial experiments. Biometrika, 33, 305-325.

Touitou, E., Gilhar, D., Alhaique, F., Memoli, A., Riccieri, F. M., & Santucci, E. (1992). Ascorbic acid in aqueous solution: Bathochromic shift in dilution and degradation. International Journal of Pharmaceutics,

, 85-87.