Wednesday, October 2, 2019
Stability and bioavailability of different erythromycin derivatives :: essays research papers
1. Introduction Erythromycin is one of the most common used macrolide antibiotics. Over the years after Abbott introduced Erythrocin ® (erythromycin stearate) into the market, several generics and new brands have been introduced – generics in the form of different 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 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 Contents 1. Introduction     2 2. Erythromycin – a brief chemical description     4 2.1 Crystal structure and hygroscopicity     7 2.2 Mechanism of action     8 3. Derivatives of erythromycin base     9 3.1 Erythromycin stearate     10 3.2 Erythromycin ethyl succinate     10 3.3 Erythromycin estolate     11 3.4 Comparison between erythromycin base and estolate     13 4 Chemical derivatives of erythromycin     13 4.1 Roxithromycin     13 4.2 Clarithromycin     14 4.3 Azithromycin     14 4.4 Dirithromycin     15 4.5 Flurithromycin     16 4.6 Comparison of properties among the newer macrolides     17 5 Discussion and conclusions     19 References     21 2. Erythromycin – a brief chemical description Figure 2.1 Advertisement for eryped ® [3] Erythromycin belongs to the chemical group of macrolide antibiotics (macros [greek] = great, -olid as the suffix for lactones). It's microbiological activity mainly covers bacterial infections of the respiratory tract and other infections with gram positive bacteria. In the case of erythromycin base, the 14-linked lactone ring (Erythronolid) is conjugated with one basic 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) [2] Erythromycin was first discovered in 1952 in Streptomyces erythreus. The spectrum of activity is equal to penicillin. The antibiotic activity is linked to the presence 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. [8] Stability 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]
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