Stability and bioavailability of different erythromycin derivatives :: essays research papers

1. IntroductionErythromycin is one of the most common apply macrolide antibiotics. Over the years after Abbott introduced Erythrocin (erythromycin stearate) into the market, several generics and new brands have been introduced &8211 generics in the form of antithetic drug formulations and new brands in the form of different erythromycin salts.All these derivatives have the same pharmacodynamics and mechanism of action, but differ tremendously in their pharmacokinetics.This paper will give an introduction and a legal brief overview in the different stabilities and pharmacokinetics of the erythromycin salts and an introduction into new approaches in the field of macrolide antibiotics.Table of Contents1. Introduction22. Erythromycin &8211 a brief chemic description42.1 Crystal structure and hygroscopicity72.2 Mechanism of action83. Derivatives of erythromycin base93.1 Erythromycin stearate103.2 Erythromycin ethyl succinate103.3 Erythromycin estolate113.4 Comparison between erythromy cin base and estolate134 Chemical derivatives of erythromycin134.1 Roxithromycin134.2 Clarithromycin144.3 Azithromycin144.4 Dirithromycin154.5 Flurithromycin164.6 Comparison of properties among the newer macrolides175 Discussion and conclusions19References212. Erythromycin &8211 a brief chemical descriptionFigure 2.1 advertising for eryped 3Erythromycin belongs to the chemical group of macrolide antibiotics (macros greek = great, -olid as the suffix for lactones). Its microbiological activity mainly covers bacterial infections of the respiratory tract and other infections with gram positive bacteria. In the slickness of erythromycin base, the 14-linked lactone ring (Erythronolid) is conjugated with one underlying amino sugar (Desopamine) and one neutral sugar (Cladinose).Figure 2.2 Erythromycin base showing the aglycon (red), the basic amino sugar (green), and the neutral sugar (blue) 2Erythromycin was first discovered in 1952 in Streptomyces erythreus. The spectrum of activity i s equal to penicillin. The antibiotic activity is linked to the comportment of the desoxy sugars.There are three known forms of erythromycin. The structure of erythromycin-A is the most common used in formulations and differs from erythromycin-B in the hydroxyl-group in position 13 of the lactone ring. Erythromycin-C is missing the methoxy-group in the cladinose sugar. 8Stability problems first were discovered when Erythrocin was found to contain not the declared amount of erythromycin stearate.The first stability problem with erythromycin is because of its deliquescence. This could be prevented if erythromycin is stored under accurate conditions.Erythromycin has a poor water solubility and solutions decompose quicker if temperature is increased. Figure 2.1 shows the chemical degradation of erythromycin. The formation of the hemiketal is a dehydration and leads to the inactivation and loss of antibiotic activity. This step is highly pH sensitive.Figure 2.3 Chemical degradation and inactivation of erythromycin 4