Chapter One - Azithromycin
Section snippets
Background
A team of researchers at the Croatian pharmaceutical company Pliva, led by Dr. Slobodan Đokić, discovered azithromycin in 1980. It was patented in 1981. Pfizer launched azithromycin under Pliva's license in other markets under the brand name Zithromax in 1991. After several years, the U.S. Food and Drug Administration approved AzaSite, an ophthalmic formulation of azithromycin, for the treatment of eye infections [1].
Systematic chemical names [2–5]
(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-(2,6-dideoxy-3-C-3-O-dimethyl-α-l-ribo-hexopyranosyloxy)-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-(3,4,6-tride-oxy-3-dimethylamino-β-d-xylo-hexopyranosyloxy)-1-oxa-6-aza-cyclopentadecan-15-one dehydrate.
(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-15-oxo-11-{[3,4,6-trideoxy-3-(dimethylamino)-β-d-xylo-]oxy}-1-oxa-6-azacyclopentadec-13-yl 2,6-dideoxy-3-C-methyl-3-O-methyl-α-l
Methods of Preparation of Azithromycin
Azithromycin (5) was prepared from erythromycin A [9], [10] by treating the erythromycin (1) in methanol with hydroxylamine hydrochloride and a base at reflux temperature for 10 h to form oxime (2). The oxime was isolated, purified, and subjected to Beckmann's rearrangement to obtain the intermediary (6,9-iminoether) (3) (Scheme 1.1) in aqueous acetone in the presence of p-toluenesulfonyl chloride and base for 2 h at 5 °C (and 2 h more at room temperature). The iminoether was reduced to the
Specific optical rotation [5,21]
[α]20 − 45° to − 49° (anhydrous substance) (C = 1 in anhydrous ethanol R)
[α]20 − 37° (C = 1 in CHCl3)
Ionization constant [22]
pKa = 7.34
Solubility characteristics [21]
Azthiromycin is practically insoluble in water and freely soluble in anhydrous ethanol and methylene chloride.
Partition coefficient
The octanol/water partition coefficient (Kow) of azithromycin was 0.65 at 20 °C and pH 7 [23]. Adsorption isotherm studies indicated that the thermodynamic data revealed that the adsorption of azithromycin on the surface of zinc was endothermic, spontaneous, and consistent with the
IR spectrum of Azithromycin
The IR spectra of the drug were obtained in the solid state using 90 g/l solutions in methylene chloride [21], [34]
HPLC drug chromatogram
The principal peak in the HPLC drug chromatogram obtained with test solution was similar in retention time and size to the principal peak in the chromatogram obtained with reference solution [21], [34].
Impurity Analysis [47]
The specified impurities (A, B, C, D, E, F, G, H, I, K, J, L, M, N, O, and P) of azithromycin were determined using liquid.
(A) R1 = OH, R2 = R6 = H, R3 = R4 = R5 = CH3: 6-demethylazithromycin,
(B)
Stability
El-Gindy et al. [75] developed a validated stability-indicating HPLC method for the analysis of azithromycin (AZ) and its related compounds in raw materials and capsules. The stability of AZ was studied under accelerated acidic, alkaline, and oxidative conditions. The major peak detected from the degradation of AZ in alkaline and acidic conditions was decladinosylazithromycine, while azithromycin N-oxide was detected from the oxidative degradation. Long-term stability studies for capsule and
An overview
Azithromycin is the member of macrolide antibiotics. It is semisynthetic derivatives of erythromycin. Azithromycin differs from erythromycin by the addition of a methyl-substituted nitrogen atom into the lactone ring. This structural modification improved acid stability and tissue penetration and broaden the spectrum of activity. Macrolides generally cover a wide range of Gram-positive and Gram-negative bacterial species including intracellular pathogens such as Chlamydia and Legionella. They
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