Clarithromycin hydrochloride 3.5-hydrate

Abstract

The absolute configuration was determined for the title compound, C38H70NO13+·Cl−·3.5H2O. The cation contains a 14‐membered macrocyclic lactone and two sugars, namely cladinose and desos­amine. The six‐membered rings of the sugars adopt chair conformations. The structure is stabilized by strong hydrogen bonds, with O⃛O distances in the range 2.486 (9)–2.830 (5) Å; other distances are N⃛O = 2.860 (5), N⃛Cl = 3.134 (4) and O⃛Cl = 3.303 (4) Å.

Polymorphic Transformation of Antibiotic Clarithromycin Under Acidic Condition

“…When form A crystals were washed with distilled water and stored at 37°C under wet condition, its appearance changed from glossy one to white one within 4 h. X‐ray powder diffraction patterns of the white crystals, named form B (Fig. d), was almost identical to that of CAM hydrochloride salt crystal, indicating that these are same crystal form. Form B was not transformed further even after the storage at 37°C for at least 3 days under wet condition.…”

“…The chloride ion in form A may be in equilibrium between ionically bonded state to the dimethyl aminomethyl moiety of CAM and freely diffusing state in the large solvent region in the crystal. Because the chloride ion in form B crystal structure is fixed by ionic bond with dimethyl aminomethyl moiety of CAM, the transformation from form A to form B would be rapid if the ratio of chloride ion bonded to the dimethyl aminomethyl moiety is high in form A crystal. The concentration of chloride ion in hydrochloric acid solution is higher as pH decreases, and the ratio of chloride ion bonded to the dimethyl aminomethyl moiety would be also higher at lower pH.…”

“…CAM, using together with amoxicillin and proton pump inhibitor (PPI), is recommended as the first‐line treatment choice to eradicate Helicobacter pylori , which is one of the etiologic factor of gastric carcinoma in human stomach . Eight crystal forms of CAM are reported so far: form 0 (ethanol solvate), form I, form II, form III (acetonitrile solvate), form IV (hydrate), form V, the hydrochloride salt, and the methanol solvate . Of these crystal forms, most stable form II is applied for clinical use in tablet and dry syrup formulations .…”

Clarithromycin form I determined by synchrotron X-ray powder diffraction

“…Clarithromycin (CAM) is a 14-membered semisynthetic macrolide antibiotic widely used for the treatment of infections with various bacteria, including chlamydia, mycoplasma and Helicobacter pylori. CAM exists in eight different crystal forms, designated form 0 (ethanol solvate; Spanton et al, 1999), form I (Liu et al, 1999), form II (Liu & Riley, 1998), form III (acetonitrile solvate; Liu et al, 2003), form IV (water solvate; Avrutov et al, 2003), form V (Gruss, 2008), the hydrochloride salt (Parvez et al, 2000) and the methanol solvate (Iwasaki et al, 1993). Tablet and dry-syrup formulations using form II crystals are in clinical use (Yajima et al, 1999(Yajima et al, , 2002.…”

Clarithromycin monohydrate: a synchrotron X-ray powder study

“…For information relating to the pharmaceutical properties of CAM, see: Yajima et al (1999Yajima et al ( , 2002; Fujiki et al (2011); Liu et al (1999). For related structures, see form I, anhydrate); Jin et al (2011; form 0, ethanol solvate); Stephenson et al (1997;form II, anhydrate); Liang & Yao (2008; form III, acetonitrile solvate); Parvez et al (2000; hydrochloride salt); Iwasaki et al (1993;methanol solvate).…”