Ology Center of Wielkopolska, 15 Garbary Str., 61-866, Poznan, Poland. two Department of PKCε Modulator Biological Activity pharmaceutical Chemistry, K. Marcinkowski University of Healthcare Sciences, 6 Grunwaldzka Str., 60-780, Poznan, Poland. 3 To whom correspondence must be addressed. (e-mail: [email protected])technological course of action and storage ought to reduce the danger of excessive drug decay and lead to reduction of economical costs of manufacture (1). In heterogeneous systems, such as solids, drug degradation is mainly dependent on relative air humidity (RH) and temperature level. Temperature could be the primary element affecting drug’s stability by inducing thermal acceleration of chemical reactions. RH also plays a function in catalyzing chemical degradation, mainly by two unique mechanisms: adsorption onto the drug surface with consequent dissolution of an active ingredient inside the formed moisturesorbed layer and the direct participation in chemical course of action, as a substrate, leading to hydrolysis, hydration, isomerization, cyclization, and also other bimolecular reactions. hydrolysis would be the most normally encountered drug degradation reaction in solid state. Hence, the substances liable to hydrolysis must be investigated with reference to their sensitivity to temperature and RH variations. This applies specifically to compounds containing ester, lactone, lactam, amide, imide, peptide, or glycosidic bonds (two). Angiotensin-converting enzyme inhibitors (ACE-I) are widely made use of for the therapy of cardiovascular system-related illnesses (three). This pharmaceutical class contains among other folks: SIRT2 Activator Storage & Stability 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, nevertheless it also increases their susceptibility to hydrolysis and to other above-mentioned bimolecular reactions. This appears unfavorable from the clinical point of view, since the premature, ex vivo hydrolysis to diacidic kind, caused one example is by improper storage, could deteriorate their pharmacological impact by the impairment of their absorption. For this reason, the ester-type ACE-I must be subjected to detailed stability studies in order to evaluate their sensitivity to temperature and RH adjustments since these components can raise hydrolysis (4). The relevant stability information have been located for the following ACE-I: ENA (5), MOXL (6), QHCl (7, eight), and BEN (9). They have been verified to be unstable under improved RH and temperature situations and their degradation impurities have been also identified. BEN was identified to undergo hydrolysis to form benazeprilat (9), ENA made diketopiperazine (DKP) derivative just after intramolecular cyclization irrespective of RH situations (5), and MOXL formed DKP derivative below dry air conditions although below RH 76.four DKP derivative and moexiprilat (six), and QHCl was evidenced to form three degradation goods: DKP, quinaprilat, and quinaprilat DKP derivative (7, 8). Furthermore, in our research 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.
