Abstract
Our interest in calculating the thermodynamic data by means of the Arrhenius equation was based on two observations: (a) the thermal death time increases considerably when the bioindicators Bacillus subtilis var. niger and Bacillus stearothermophilus are sterilized in nonaqueous hydrophilic solutions as found in propylene glycol (PG) with low water concentrations; and (b) the inactivation kinetics of Bac. stearothermophilus does not follow a first-order reaction. The frequency factor A and the entropy of activation ΔS* have the highest values in water and the lowest value in PG; ΔS* for Bac. stearothermophilus in water is 812 J/mol K; however, in PG it is −9.6 J/mol K. A good correlation between ΔS* and the enthalpy ΔH* is found, indicating possible protein denaturation during thermal inactivtion. The moderate positive and negative ΔS* values in PG and PG with low water concentrations might be explained by (a) rigid conformation of proteins due to stabilization and (b) slow reaction, making the complex a less probable structure, when the activated complex is built only under considerable rearrangement of the structure of the reactant molecules. The opposite was observed with the Z and Z* values, the latter being defined as Z values of nonlogarithmic survival curves. The Z values increase with increasing concentrations of PG, i.e., for Bac. subtilis of Z = 8°C in water up to Z = 23°C in PG and for Bac. stearothermophilus of Z = 6°C up to Z* = 27°C. The calculated free enthalpy of activation ΔG* is about 100 kJ/mol for both spore formers tested in the mentioned suspending medium. The ΔG* values found are similar to literature data of the denaturation of most proteins. These thermodynamic data do not explain the enormous increase of resistance in PG–water mixtures.
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REFERENCES
S. Urban, Th. Cavanak, I. Schiller, and H. Sucker. Pharm. Ind. 41:886–888 (1979).
P. Ruffieux. Thesis, University Basel, Basel, 1983.
B. Philipp. Thesis, University Basel, Basel, 1985.
B. Philipp and H. Sucker. Pharm. Ind. 50:360–363 (1988).
B. Philipp and H. Sucker. Pharm. Ind. 50:735–738 (1988).
PDA, Validation of Steam Sterilization Cycles, Technical Monograph No. 1, Parenteral Drug Association, Philadelphia, 1978.
B. Philipp and H. Sucker. Pharm. Ind. 51:85–88 (1989).
USP XXI. The United States Pharmacopoeia, XXIst ed., United States Pharmacopoeial Convention, Inc., Rochville, Md., 1985, pp. 908–909.
USP XXI. The United States Pharmacopoeia, XXIst ed., United States Pharmacopoeial Convention, Inc., Rockville, Md., 1985, NF XVI, pp. 1589–1590.
USP XXI. The United States Pharmacopoeia, XXIst ed., United States Pharmacopoeial Convention, Inc., Rockville, Md., 1985, Supplement II, pp. 1814–1819.
K. H. Wallhäusser. Praxis der Sterilisation, Desinfektion—Konservierung. 4. Aufl., Georg Thieme Verlag, Stuttgart, 1988, pp. 211–355.
A. D. Russell. The Destruction of Bacterial Spores, Academic Press, London, 1982, pp. 31–89.
M. J. Akers, I. A. Attia, and K. E. Avis. J. Parent. Drug Assoc. 33:195–200 (1979).
A. N. Martin, J. Swarbrick, and A. Cammarata. Physical Pharmacy, 3rd ed., Lea & Fibiger, Philadelphia, 1983, pp. 352–398.
A. Cornish-Barden. Principle of Enzyme Kinetics, Butterworths, 1975, pp. 9–13.
R. A. Nash. J. Parent. Sci. Technol. 39:251–256 (1985).
H. T. Hoskins. J. Parent. Sci. Technol. 35:285–292 (1981).
E. V. Hoxey, C. J. Soperand, and D. J. G. Davies. J. Pharm. Pharmacol. 35:52p (1983).
Y. J. Wang, G. D. Leesman, M. E. Lipstein, H. I. Basch, and D. C. Monkhouse. J. Parent. Sci. Technol. 38:78–82 (1984).
Ch. Tanford. Physical Chemistry of Macromolecules, John Wiley and Sons, New York, 1961, pp. 624–639.
B. Rosenberg, G. Kemeny, R. C. Switzer, and T. C. Hamilton. Nature 232:472–473 (1971).
M. Joly. A Physico-Chemical Approach to the Denaturation of Proteins, Academic Press, New York, 1965, pp. 191–260.
H. L. Sadoff. In G. W. Gould and A. Hurst (eds.), The Bacterial Spore, Academic Press, London, 1969, Vol. I, pp. 275–299.
W. G. Murrell. In H. S. Levinson, A. L. Sonenshein, and D. J. Tipper (eds.), Sporulation and Germination, Am. Soc. Microbiol., Washington, D.C., 1981, pp. 64–77.
J. A. Lindsay. Curr. Microbiol. 16:265–269 (1988).
P. H. Khoury, S. J. Lombardi, and R. A. Slepecky. Curr. Microbiol. 15:15–19 (1987).
Ph. Eur. European Pharmacopoeia, 2nd ed., Maisonneuve S.A., France, 1983, Vol. I, pp. IX.1-1–IX.1.-4.
FIP, Fédération Internationale Pharmaceutique 4. Bericht. Pharmazie 42:854–857 (1987). resp. J. Parent. Sci. Technol. 43:226-230 (1989).
USP XXI. The United States Pharmacopoeia, XXI ed., United States Pharmacoepoeial Convention, Inc., Rockville, Md., 1985, Supplement IV, Chapter 1035, pp. 2256–2257.
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Philipp, B., Sucker, H. Heat Sterilization of Bioindicators in Propylene Glycol and Propylene Glycol–Water Mixtures: Arrhenius Equation, Thermodynamic Data, and Z Values. Pharm Res 7, 1273–1277 (1990). https://doi.org/10.1023/A:1015989905950
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DOI: https://doi.org/10.1023/A:1015989905950