A kinetic and mechanistic study of the hydrolysis of camptothecin and some analogues.
It was shown that the lactone was converted to the carboxylate in a pH-dependent equilibrium, and this finding strongly suggests that the mechanism of lactone ring hydrolysis involved acyl cleavage rather than alkyl cleavage.
Chemical Stability of Pharmaceuticals: A Handbook for Pharmacists
PRINCIPLES. Stability Calculations. Interpretation of Kinetic Data. Hydrolysis and Other Acyl Transfers. Oxidation and Photolysis. Solid-State Chemical Decompostion. Strategy and Tactics of Stability…
Stability of Drugs and Dosage Forms
The stability of Peptide and Protein Pharmaceuticals and their applications are regulated by the European Medicines Agency and the United Kingdom government.
Effect of Cyclodextrin Charge on Complexation of Neutral and Charged Substrates: Comparison of (SBE)7M-β-CD to HP-β-CD
The studies suggested that on average two sulfonates out of seven may be involved in forming ionic attraction or repulsion effects with the positive charges on prazosin and papaverine, or negative charges of ionized naproxen and warfarin.
Pharmaceutical applications of cyclodextrins. 2. In vivo drug delivery.
This Review primarily focuses on newer findings concerning cyclodextrin derivatives which are likely to receive regulatory acceptance due to improved aqueous solubility and safety profiles as compared to the unmodified cyclodexypropyl-beta-cyclodextrins.
Estimating the maximal potential for intestinal lymphatic transport of lipophilic drug molecules
Prodrug strategies to overcome poor water solubility.
Synthesis and evaluation of some water-soluble prodrugs and derivatives of taxol with antitumor activity.
- A. E. Mathew, M. R. Mejillano, J. Nath, R. Himes, V. Stella
- Chemistry, BiologyJournal of Medicinal Chemistry
The 2'-analogues appear to behave as prodrugs and have the potential to be developed as chemotherapeutic agents and the greatest antitumor activity compared to the other analogues.
Dissolution kinetics of carboxylic acids I: effect of pH under unbuffered conditions.
- K. G. Mooney, M. Mintun, K. Himmelstein, V. Stella
- Materials ScienceJournal of pharmaceutical sciences
A model for the initial steady-state dissolution rate of a monoprotic carboxylic acid was derived from Fick's second law of diffusion, and was found to predict the dissolution rates of these acids accurately as a function of the bulk solution pH.
Your prodrug releases formaldehyde: should you be concerned? No!
The perspective on the apparent concern with release of formaldehyde as a by-product of in vivo bioconversion of selective prodrugs is presented, and it is suggested that in comparison to the total amount of daily endogenous formaldehyde production from metabolism, and exogenous exposure from food and the environment, the amount generated by pro drugs is minute and is unlikely to cause any systemic toxicity in humans.