Crystal structure and solid-state studies of aged samples of tienoxolol, an API designed against hypertension.
Aging of drug molecules is generally studied following regulatory procedures, i.e. under forced conditions and for relatively limited storage time; therefore naturally aged samples are rare and provide scientific reference data beyond regulatory considerations. Tienoxolol was studied after 25 years of storage in the dark under ambient conditions. About 86% of the samples still consisted of tienoxolol and the main impurity (13%) was caused by the hydrolysis of the ester moiety. Protection from humidity is therefore important. Other sensitive groups containing nitrogen and sulfur appear to be quite stable with less than 0.8% conversion over 25 years. In addition, the crystal structure has been solved. Tienoxolol orange needles were found to crystallize in the orthorhombic non-centrosymmetric space group Iba2, indicating that the crystal is a racemic compound. The unit cell parameters at room temperature are a=10.069(5)Å, b=45.831(10)Å, and c=9.822(5)Å and the unit cell volume is 4533(3)Å(3) with Z=8.
EAD Physico-chimie Industrielle du Médicament, Faculté de Pharmacie, Université Paris Descartes, 4, Avenue de l'Observatoire, 75006 Paris, France.
Nathalie
N
Mahé
Bernard
B
Do
Béatrice
B
Nicolaï
Ivo B
IB
Rietveld
Maria
M
Barrio
Josep-Lluís
JL
Tamarit
René
R
Céolin
Christophe
C
Guéchot
Jean-Marie
JM
Teulon
D000959:Antihypertensive Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D018360:Crystallography, X-Ray; D004355:Drug Stability; D004356:Drug Storage; D006813:Humidity; D006868:Hydrolysis; D008958:Models, Molecular; D015394:Molecular Structure; D033362:Powder Diffraction; D011412:Propanolamines / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
D000959:Antihypertensive Agents; D011412:Propanolamines; D014867:Water; C056983:tienoxolol