Ology Center of Wielkopolska, 15 Garbary Str., 61-866, Poznan, Poland. two Division of Pharmaceutical Chemistry,

Ology Center of Wielkopolska, 15 Garbary Str., 61-866, Poznan, Poland. two Division of Pharmaceutical Chemistry, K. Marcinkowski University of Medical Sciences, six Grunwaldzka Str., 60-780, Poznan, Poland. three To whom correspondence should be addressed. (e-mail: [email protected])technological procedure and storage should really decrease the threat of excessive drug decay and lead to reduction of economical expenses of manufacture (1). In heterogeneous systems, including solids, drug degradation is mainly dependent on relative air humidity (RH) and temperature level. Temperature is the major factor affecting drug’s stability by inducing thermal acceleration of chemical reactions. RH also plays a function in catalyzing chemical degradation, mostly by two various mechanisms: adsorption onto the drug surface with consequent dissolution of an active ingredient inside the formed moisturesorbed layer plus the direct participation in chemical approach, as a substrate, leading to hydrolysis, hydration, isomerization, cyclization, and other bimolecular reactions. Hydrolysis would be the most ALDH1A2 Protein Molecular Weight generally encountered drug degradation reaction in solid state. Hence, the substances liable to hydrolysis needs to be investigated with reference to their sensitivity to temperature and RH variations. This applies especially to compounds containing ester, lactone, lactam, amide, imide, peptide, or glycosidic bonds (two). Angiotensin-converting enzyme inhibitors (ACE-I) are widely employed for the therapy of cardiovascular system-related illnesses (three). This pharmaceutical class includes amongst other people: imidapril hydrochloride (IMD), enalapril maleate (ENA), moexipril hydrochloride (MOXL), quinapril hydrochloride (QHCl), and benazepril hydrochloride (BEN), that are prodrug, ester-type, potent, long-acting, oral, dicarboxylate-containing agents which are hydrolyzed in vivo to their active, diacidic metabolites. The presence of ester functional in prodrug forms1530-9932/13/0300-1199/0 # 2013 American Association of Pharmaceutical Scientists1200 increases their lipophility and improves their pharmacokinetic profiles, however it also increases their susceptibility to hydrolysis and to other above-mentioned bimolecular reactions. This appears unfavorable in the clinical point of view, because the premature, ex vivo hydrolysis to diacidic form, caused for example by improper storage, could deteriorate their pharmacological effect by the impairment of their absorption. For this reason, the ester-type ACE-I need to be subjected to detailed stability research so that you can evaluate their sensitivity to temperature and RH adjustments since these components can increase hydrolysis (4). The relevant stability data have been identified for the following ACE-I: ENA (5), MOXL (six), QHCl (7, 8), and BEN (9). They have been proven to be unstable under increased RH and temperature circumstances and their degradation impurities happen to be also identified. BEN was found to undergo hydrolysis to form benazeprilat (9), ENA developed diketopiperazine (DKP) derivative immediately after intramolecular cyclization irrespective of RH IFN-beta Protein Species conditions (five), and MOXL formed DKP derivative beneath dry air conditions though under RH 76.four DKP derivative and moexiprilat (six), and QHCl was evidenced to type three degradation goods: DKP, quinaprilat, and quinaprilat DKP derivative (7, 8). Furthermore, in our studies with IMD, we’ve got shown that this drug follows two parallel degradation pathways under the situations of T=363 K, RH 76.four , i.e., hydrolysis of ester bon.