Leon Lachman

Bio: Leon Lachman is an academic researcher from University of Wisconsin-Madison. The author has contributed to research in topics: Xanthine & Compatibility testing. The author has an hindex of 3, co-authored 5 publications receiving 49 citations.

Inhibition of Hydrolysis of Esters in Solution by Formation of Complexes I

Abstract: A new approach to possible preservation of drugs undergoing hydrolytic degradation is presented. It is shown that the rate of hydrolysis of benzocaine in aqueous solution can be substantially inhibited by addition of caffeine which has previously been shown to complex with this drug. Presence of two and one‐half per cent of caffeine in the system resulted in reduction of the hydrolytic rate to less than one‐fifth of that in absence of the xanthine. Mathematical analysis of the results obtained indicates that the complexed form of the drug does not undergo, surprisingly, any perceptible cleavage at the ester linkage.

Inhibition of hydrolysis of esters in solution by formation of complexes. II. Stabilization of procaine with caffeine

Abstract: A study of the tetracaine hydrochloride-caffeine system has shown that the hydro-lytic rate of the ester component is reduced in the presence of the xanthine in a manner similar to that of the benzocaine-caffeine and the procaine hydrochloride-caffeine systems. Evidence seems to indicate however, that the stoichiometry of the complexing reaction is different from the previous cases. The data obtained are best rationalized on the basis that tetracaine ion forms two types of complexes in solution, the first consisting of two caffeine molecules to one tetracaine ion and the second of two tetracaine ions to one caffeine molecule. According to the present findings, addition of one-half per cent caffeine to a similar concentration of tetracaine hydro-chloride in water, for example, reduces the hydrolytic rate by thirty-five per cent. In the presence of two per cent caffeine, the rate of hydrolysis is only one-third that of the caffeine-free solution.

Reactive Impurities in Excipients: Profiling, Identification and Mitigation of Drug–Excipient Incompatibility

Abstract: Reactive impurities in pharmaceutical excipients could cause drug product instability, leading to decreased product performance, loss in potency, and/or formation of potentially toxic degradants. The levels of reactive impurities in excipients may vary between lots and vendors. Screening of excipients for these impurities and a thorough understanding of their potential interaction with drug candidates during early formulation development ensure robust drug product development. In this review paper, excipient impurities are categorized into six major classes, including reducing sugars, aldehydes, peroxides, metals, nitrate/nitrite, and organic acids. The sources of generation, the analytical method for detection, the stability of impurities upon storage and processing, and the potential reactions with drug candidates of these impurities are reviewed. Specific examples of drug–excipient impurity interaction from internal research and literature are provided. Mitigation strategies and corrective measures are also discussed.

Stability Aspects of Preformulation and Formulation of Solid Pharmaceuticals

Abstract: (1984). Stability Aspects of Preformulation and Formulation of Solid Pharmaceuticals. Drug Development and Industrial Pharmacy: Vol. 10, No. 8-9, pp. 1373-1412.

4 Proximity Effects and Enzyme Catalysis

Abstract: Publisher Summary A characteristic of all enzymic reactions involving specific substrates is the initial formation of an enzyme–substrate complex. The rate constant for this process may be diffusion controlled. This chapter evaluates the extent of rate acceleration brought about by propinquity in terms of rate accelerations found in enzymic reactions. The chapter discusses the approach of physical organic models. The milieu and conformational-strain effects are considered in the chapter when inseparable from the propinquity effect. Evaluation of the milieu effect is difficult. Solvent and electrostatic effects may be studied with appropriate models, but the chemist is unable to provide a stereospecific heterogeneous reaction medium. This division into three categories is of course rather arbitrary. The propinquity effect must also influence the nature of the milieu at the active site and by steric interference, etc., could contribute to the conformational-strain effect.

Molecular complex consisting of two typical external medicines: intermolecular interaction between indomethacin and lidocaine.

Abstract: The molecular complex formed between indomethacin (IDM) and lidocaine (LDC), which are typical external medicines, was studied. A thermal analysis, microscopic study and phase solubility technique suggested intermolecular interaction between IDM and LDC. The phase solubility profiles with IDM and LDC were classified as A(L)-type, indicating the formation of a 1 : 1 stoichiometric molecular complex. The apparent stability constant (K(S)), calculated from the slope and the intercept, was 4478.9 M(-1). A molecular ion peak was detected at 592.2 (m/z) from fast-atom bombardment-MS measurements, which was in accordance with the sum of the molecular weight for IDM (M(W): 357.81) and LDC (M(W): 234.38). The changes of IR spectra in the C=O stretching region showed that each intact hydrogen bond network was collapsed in the IDM-LDC system and strong interaction between IDM and LDC formed after their kneading. From the (1)H-NMR analyses, it was estimated that the dominant interactive site was the IDM carboxylic acid group which associated with the LDC diethyl amino group non-covalently.