[Methods of standardization of drug assortments for special situations and catastrophic events]. / Methodik der Standardisierung des Arzneimittelsortiments für Ausnahmesituationen und Katastrophenbedingungen.

A complex to the problems of drug standardization for special situations and catastrophic events requires a definition of the drug assortment in qualitative and quantitative terms. For that purpose the publication submitted gives a description of the methodology used.

[The kinetics of neostigmine degradation in aqueous solution]. / Zur Kinetik des Neostigminabbaus in wässriger Lösung.

The concentration course of the degradation products of aqueous temperature-stressed solutions of neostigmine bromide (1) shows, that 1 simultaneously is hydrolyzed to 3-hydroxyphenyltrimethylammonium bromide (2) and demethylated to 3-dimethylaminophenyldimethylcarbamate (4). The ester hydrolysis is the rate-determining predominant reaction and of pseudo first-order. Under temperature-stressed conditions only, the demethylation to 4 followed by consecutive reactions proceeds at a measurable rate. The kinetic parameters of the ester hydrolysis calculated from the results of isothermic short-term tests permit the prediction of a five-year stability of 2% neostigmine solutions in the therapeutically relevant pH-value range from 3 to 7. On the basis of the kinetic results the possible reaction mechanisms and the influence of selected components on the rate of the hydrolysis and demethylation are discussed.

[The structure of degradation products of neostigmine bromide]. / Zur Struktur der Abbauprodukte von Neostigminbromid.

In aqueous temperature-stressed solutions of neostigmine bromide besides the known product of hydrolysis additional degradation products were discovered, detected by TLC and HPLC. By means of spectroscopic studies (1H-NMR, IR, UV, MS) and elemental analysis the isolated decomposition products were identified as 3-hydroxyphenyltrimethylammonium bromide (2), 3-dimethylaminophenol (3), 3-dimethylaminophenyl-dimethylcarbamate (4), 3-methylaminophenyl-dimethylcarbamate (5), 3-aminophenyl-dimethylcarbamate (6) and 4 (resp. 6)-bromo-3-dimethylaminophenyl-dimethylcarbamate (7). The structures of 2-7 were confirmed by comparison with synthesized authentic compounds.

[The stability of pilocarpine hydrochloride in eyedrops]. / Zur Stabilität von Pilocarpinhydrochlorid in Augentropfen.

This study investigate the kinetics of the degradation of pilocarpine in aqueous solutions within the therapeutically relevant pH-value range from 2.9 to 6.5. A linear system of first order equations for the kinetics of complex pilocarpine degradation can be derived from the concentration course of decomposed products determined by HPLC. The kinetic parameters calculated from the results of isothermic short-term tests permit the prediction of a five-year durability of non-buffered pilocarpine eye drops, if their pH-value is in the maximum stability range of less than or equal to 4. Comparison of non-stereoselective photometric results with the hplc results shows the inappropriateness of the results of conventional spectrophotometric analysis in the presence of epimeric decomposition products for the interpretation of kinetic reaction and, accordingly, for evaluating stability. Contrary to previous studies, the results indicate a reversibility of epimerization in temperature-stressed isopilocarpine solutions.