O the regulatory obligation to make sure the invariability of qualitative and
O the regulatory obligation to make sure the invariability of qualitative and quantitative composition during storage, but also it contributes for the economization and optimization of manufacture course of action, particularly in case of unstable active pharmaceutical ingredients; the decomposition of which decreases their productivity. The aspect of drug stability is crucial also in the clinical point of view because the loss of active ingredient, triggered by degradation, contributes for the deterioration of remedy efficiency. Drug’s stability could be influenced by a variety of components, such as environmental circumstances (temperature, light, air humidity), package elements, or substance chemical properties. Hence, the determination of proper parameters forThe Oncology 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. 3 To whom correspondence ought to be addressed. (e-mail: [email protected])technological course of action and storage need to decrease the threat of excessive drug decay and lead to reduction of economical expenditures of manufacture (1). In heterogeneous systems, such as solids, drug degradation is largely dependent on relative air humidity (RH) and temperature level. Temperature could be the major element affecting drug’s stability by inducing thermal acceleration of chemical Adenosine A1 receptor (A1R) Agonist drug reactions. RH also plays a role in catalyzing chemical degradation, mainly by two distinct mechanisms: adsorption onto the drug surface with consequent dissolution of an active ingredient inside the formed moisturesorbed layer and also the direct participation in chemical course of action, as a substrate, top to hydrolysis, hydration, isomerization, cyclization, and also other bimolecular reactions. Hydrolysis is the most normally encountered drug degradation reaction in strong state. Hence, the substances liable to hydrolysis need to 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 (2). Angiotensin-converting enzyme inhibitors (ACE-I) are widely utilized for the therapy of 5-HT3 Receptor Agonist Compound cardiovascular system-related illnesses (3). This pharmaceutical class contains amongst other folks: imidapril hydrochloride (IMD), enalapril maleate (ENA), moexipril hydrochloride (MOXL), quinapril hydrochloride (QHCl), and benazepril hydrochloride (BEN), which 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, since the premature, ex vivo hydrolysis to diacidic type, caused for example by improper storage, could deteriorate their pharmacological impact by the impairment of their absorption. Because of this, the ester-type ACE-I needs to be subjected to detailed stability studies in order to evaluate their sensitivity to temperature and RH changes considering the fact that these factors can raise hydrolysis (four). The relevant stability information happen to be located for the following ACE-I: ENA (five), MOXL.
