The effects of pH and PEG 400-water cosolvents on oxytetracycline-magnesium complex formation and stability.
The effects of pH and PEG 400 on the stoichiometry, conformation, and stability of the magnesium-oxytetracycline (Mg+2-OTC) complex were evaluated. Circular dichroism (CD) and HPLC were used to investigate Mg+2-OTC complex formation and determine the stability of the complexes formed. The stoichiometry of the complex was determined to be a 1:1 molar ratio of Mg+2 to OTC regardless of changes in pH, in the range 7-10, and regardless of the percentage of polyethylene glycol (PEG) 400 in solution. CD showed that the conformation assumed by Mg+2-OTC complex is sensitive to changes in pH, however, little to no effect was found when the PEG 400 concentration was varied. PEG 400 was found to effect the magnitude of complexation as evident by the dependence of CD peak intensity on the cosolvent concentration in solution. The Job's method confirmed that the formation of this complex increased with increasing PEG 400 concentration and was most favored at pH 8. HPLC analyses of OTC solutions at pH 9 revealed the formation of multiple degradation products after storage at 50 degrees C. The incidence and magnitude of OTC degradation products were reduced in the presence of Mg+2 and PEG 400. Despite the HPLC results of maintained OTC stability in magnesium-complexed solutions over time, visual inspection showed these solutions to have darkened, indicating that an oxidative process is responsible for initial degradation of OTC. Therefore, the need for additional measures (i.e., antioxidants) was established to ensure the long-term stability of OTC in solution.
Tongaree
S
S
Whitehall-Robins Healthcare, Richmond, Virginia 23220, USA. tongars@ahp.com
Goldberg
A M
AM
Flanagan
D R
DR
Poust
R I
RI
D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004339:Drug Compounding; D004355:Drug Stability; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D008274:Magnesium / Q000008:administration & dosage* / Q000737:chemistry; D010118:Oxytetracycline / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols; D012997:Solvents; D013501:Surface-Active Agents; D013696:Temperature
D000900:Anti-Bacterial Agents; D012997:Solvents; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D008274:Magnesium; D010118:Oxytetracycline