Influence of hydroxypropyl beta-cyclodextrin on the stability of benzylpenicillin in chloroacetate buffer
| Autor: | Craig M. McDonald, J K Ong, V B Sunderland |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Stereochemistry
Pharmaceutical Science Beta-Cyclodextrins Acetates Buffers Medicinal chemistry Benzylpenicillin Inclusion compound Turn (biochemistry) chemistry.chemical_compound Drug Stability polycyclic compounds medicine Equilibrium constant Antibacterial agent Pharmacology chemistry.chemical_classification Cyclodextrins Cyclodextrin Chemistry beta-Cyclodextrins Penicillin G 2-Hydroxypropyl-beta-cyclodextrin Penicillin Thermodynamics medicine.drug |
| Zdroj: | The Journal of pharmacy and pharmacology. 49(6) |
| ISSN: | 0022-3573 |
| Popis: | Hydroxypropyl β-cyclodextrin (HPβCyD) has been shown to stabilize a wide variety of chemically distinct pharmaceutical entities through inclusion-complex formation between drug and cyclodextrin. The effect of HPβCyD on the acid-catalysed hydrolysis of benzylpenicillin (penicillin G) was evaluated in chloroacetate buffer at pH 2.20. At penicillin G: cyclodextrin molar concentration ratios from 1:1 to 1:10, HPβCyD effected stabilization of penicillin G by 1.56- to 5.21-fold. At all temperatures, the observed first-order rate constant (kobs) values assumed a non-linear, Michaelis-Menten type decrease as a function of increasing HPβCyD concentration. Degradation of penicillin G complexed with HPβCyD (penicillin G-HPβCyD), was approximately ninefold slower than uncomplexed penicillin G. The proportion of penicillin G degrading in either of these forms was, in turn, determined by the equilibrium constant for the complexation. The apparent thermodynamic and activation parameters for the complexation between penicillin G and HPβCyD have also been evaluated. The negative standard enthalpy change (ΔH°) for the complexation implied that the penicillin G-HPβCyD complex would be predisposed towards enhanced stability, and thus the kobs value for the hydrolysis of penicillin G decreased with reduction of temperature in these systems. The lack of difference between the enthalpies of activation (ΔH‡) for the hydrolysis of uncomplexed and complexed penicillin G seemed to be compensated by the significant difference between the entropies of activation (ΔS‡) for these hydrolytic reactions. The results indicate that HPβCyD represents a viable means of stabilization of penicillin G solutions at the pH employed in this study. |
| Databáze: | OpenAIRE |
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