Solubility and stability of tetrazepam in mixed micelles.
The solubility and stability of the chemically unstable drug tetrazepam which has poor water solubility have been studied in bile salts-phosphatidylcholine-mixed micelles (BS-PC-MM). The solubilization potential of BS-PC-MM was much higher than that of BS alone. The use of soya-PC (SPC) instead of egg-PC (EPC) increased the solubilization capacity of MM. The results of the stability studies indicated first order degradation kinetics in most cases under aerobic conditions. An Arrhenius plot could be constructed in a temperature range from 30 to 60 degrees C in sodium deoxycholate-SPC-MM (SDC-SPC-MM) as well as in phosphate buffer at pH 7.4. Sodium glycocholate-SPC-MM (SGC-SPC-MM) interfered with the degradation kinetics and displayed better stabilizing effects under both aerobic and anaerobic conditions. The addition of ascorbic acid (AA) protected tetrazepam to some extent, whereas Na2SO3 or Na2S2O5 were incompatible with it. Formulating tetrazepam in SGC-SPC-MM containing 0.1% AA resulted in a shelf stability of more than 1 year under anaerobic conditions.
Hammad
M A
MA
Christian-Albrechts-University, Department of Pharmaceutics and Biopharmaceutics, Gutenbergstrasse 76, 24118, Kiel, Germany.
Müller
B W
BW
D014151:Anti-Anxiety Agents / Q000737:chemistry*; D001569:Benzodiazepines; D001647:Bile Acids and Salts / Q000737:chemistry; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D009125:Muscle Relaxants, Central / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D012995:Solubility; D013696:Temperature; D014867:Water / Q000737:chemistry
D014151:Anti-Anxiety Agents; D001647:Bile Acids and Salts; D008823:Micelles; D009125:Muscle Relaxants, Central; D010713:Phosphatidylcholines; D014867:Water; D001569:Benzodiazepines; C005245:tetrazepam