Hypertension is considered a major public health issue due to its high prevalence and subsequent risk of cardiovascular and kidney diseases. Thus, the search for new antihypertensive compounds remains of great interest. Snake venoms provide an abundant source of lead molecules that affect the cardiovascular system, which makes them prominent from a pharmaceutical perspective. Such snake venom components include bradykinin potentiating peptides (proline-rich oligopeptides), natriuretic peptides, phospholipases A2, serine-proteases and vascular endothelial growth factors. Some heparin binding hypotensive factors, three-finger toxins and 5′ nucleotidases can also exert blood pressure lowering activity. Great advances have been made during the last decade regarding the understanding of the mechanism of action of these hypotensive proteins. Bradykinin potentiating peptides exert their action primarily by inhibiting the angiotensin-converting enzyme and increasing the effect of endogenous bradykinin. Snake venom phospholipases A2 are capable of reducing blood pressure through the production of arachidonic acid, a precursor of cyclooxygenase metabolites (prostaglandins or prostacyclin). Other snake venom proteins mimic the effects of endogenous kallikrein, natriuretic peptides or vascular endothelial growth factors. The aim of this work was to review the current state of knowledge regarding snake venom components with potential antihypertensive activity and their mechanisms of action.

Current pharmaceutical research directions tend to follow a systematic approach in the field of applied research and development. The concept of quality-by-design (QbD) has been the focus of the current progress of pharmaceutical sciences. It is based on, but not limited, to risk assessment, design of experiments and other computational methods and process analytical technology. These tools offer a well-organized methodology, both to identify and analyse the hazards that should be handled as critical, and are therefore applicable in the control strategy. Once implemented, the QbD approach will augment the comprehension of experts concerning the developed analytical technique or manufacturing process. The main activities are oriented towards the identification of the quality target product profiles, along with the critical quality attributes, the risk management of these and their analysis through in silico aided methods. This review aims to offer an overview of the current standpoints and general applications of QbD methods in pharmaceutical development.

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Objectives:The polyoxometalates are a class of inorganic compounds with controllable shapes and sizes, and with excellent properties that make them attractive for various applications. This study is aimed at the comparative UV and IR spectra of Keggin type polyoxometalates. Methods: Compounds under (UV and IR) investigations were divided into several groups to highlight similarities between compounds or classes of compounds for the same category. There are four types of saturated Keggin structures and six lacunar compounds included in this study. The study begins with the UV investigations on aqueous solutions with 10 -5 M concentration for these compounds. IR spectra were recorded as KBr pressed pellets. Results: The UV spectras presents large strong peaks between 185-195 nm corresponding to W = Od bonds, between 251-268 nm for W-O-W bridge bonds, depending on heteroatom types (As, Sb). The unsaturated cryptand ligand having Co 2+ coordinated presents the most intense peak, due to the involvement of oxygen atoms from terminal W = Od coordinative bonds with high electronic densities in coordination of W-O-Co bond. The IR spectra present many peaks that are associated as follows: for terminal bonds W = Od, 955-970 cm -1 ; for W-O-W bridging bonds, 790-910 cm -1 ; for W-O-As/Sb bonds to heteroatom, 690-760 cm -1 . Vibrations of the bonds between heteroatoms and oxygen (As/Sb-O) appear around 620-660 cm -1 . Conclusions: Similarities appear from the recorded spectra, between compounds of the same class, by category association. Very fi ne displacements of peaks that occur explain the infl uence of heteroatoms, addenda atoms or coordinated cations.

The enantioseparation of four phthalimide derivatives (thalidomide, pomalidomide, lenalidomide and apremilast) was investigated on five different polysaccharide-type stationary phases (Chiralpak AD, Chiralpak AS, Lux Amylose-2, Chiralcel OD and Chiralcel OJ-H) using neat methanol (MeOH), ethanol (EtOH), 1-propanol (PROP), 2-propanol (IPA) and acetonitrile (ACN) as polar organic mobile phases and also in combination. Along with the separation capacity of the applied systems, our study also focuses on the elution sequences, the effect of mobile phase mixtures and the hysteresis of retention and selectivity. Although on several cases extremely high resolutions (Rs > 10) were observed for certain compounds, among the tested conditions only Chiralcel OJ-H column with MeOH was successful for baseline-separation of all investigated drugs. Chiral selector- and mobile-phase-dependent reversals of elution order were observed. Reversal of elution order and hysteresis of retention and enantioselectivity were further investigated using different eluent mixtures on Chiralpak AD, Chiralcel OD and Lux Amylose-2 column. In an IPA/MeOH mixture, enantiomer elution-order reversal was observed depending on the eluent composition. Furthermore, in eluent mixtures, enantioselectivity depends on the direction from which the composition of the eluent is approached, regardless of the eluent pair used on amylose-based columns. Using a mixture of polar alcohols not only the selectivities but the enantiomer elution order can also be fine-tuned on Chiralpak AD column, which opens up the possibility of a new type of chiral screening strategy.