Ionization constants and solubility of compounds involved in enzymatic synthesis of aminopenicillins and aminocephalosporins

Abstract

The article deals with experimental determination of ionization constants and solubility for the compounds (target products, initial β-lactams, acylating agents and by-products) involved in enzymatic synthesis of some therapeutically used aminopenicillins and aminocephalosporins, namely ampicillin, amoxicillin, cephalexin, cephadroxil, cephaloglycin, cefaclor, cefprozil, cefatrizine. Methodology of investigations and the evaluation of experimental data for the determination of ionization constants and solubility of the different type electrolytes are presented. Applications of the methods based on acid-base potentiometric titration and on determination of solubility-pH dependence of assayed substances are discussed. The original data on ionization constants and solubility of amoxicillin, cefprozil, cefatrizine, cephadroxil and initial β-lactams for production of cefaclor, cefprozil and cefatrizine, as well as solubility of by-product D-(-)-p-hydroxyphenylglycine are presented. Experimentally determined parameters and constants available in the literature for all abovementioned aminopenicillins and aminocephalosporins are collected. These data might be used for choice of the conditions of both processes: the enzymatic synthesis and the isolation of the product from reaction mixture.

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Cephalexin Monohydrate

“…59 Others sources report different values for the isoelectric points, calculated on the basis of the dissociation constants evaluated in the respective study. 56,60,61 Partition and Distribution Coefficient Clarke's Analysis of Drug and Poisons reports an octanol/water coefficient (log P) for cephalexin of 0.6, which is similar to values from other sources (Drug Bank: prediction with ALOGPS program: 0.55; Hazardous Substances Data Bank: Hansch, Leo et al: 0.65). 55,62,63 Davis and Papich et al reported a log P of À1.12 64 while Kasim et al published a log P of À0.67 and a Clog P of À1.64.…”

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Amoxicillin Trihydrate

“…This upper concentration in this range could potentially affect permeability. However, the Carmellose sodium HU( 1 ) NL 23.2-160 Cellulose, microcrystalline BE( 3 ) CZ( 4 ) DE( 5-7 ) DK( [8][9][10][11] ) ES( [12][13][14][15][16] ) FI( [17][18][19] ) FR( [20][21][22] ) HR( 23 ) HU( 1,24 ) IE( 25 ) IS( 26,27 ) IT( [28][29][30][31][32] ) NL( 2,33 ) NO( 34,35 ) PT( [36][37][38][39] ) RO( [40][41][42] ) SE( 43,44 ) SK 45 [12][13][14][15][16]55,56,[68][69][70] ) FI( [17]…”