Exploring novel and fast stability or sameness evaluation tool for different categories of injectable formulations.

The establishment of drug product stability and sameness is the heart of generic formulation development. For regulatory filing, various instrumental methods are used on a case basis to establish the generic and innovator product sameness in multiple aspects. Here in the present study, we explored the applicability of the Time-correlated single photon counting (TCS-PC) technique as a fast, reliable, and nondestructive method for establishing the sameness of three different categories of injectable formulations, namely, Amphotericin B liposome for injection, enoxaparin injection, and iron sucrose injection. All three category formulations were evaluated in their native and artificially induced post degradation state to identify the discrimination power of the used instrumental techniques. The degradation of materials were confirmed by high performance liquid chromatography (HPLC). Based on the product category, pre and post-degradation samples were evaluated by selective instrumental methods like differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), fluorescence spectroscopy, particle size analysis by dynamic light scattering (DLS), small angle X-ray scattering (SAXS), Raman spectroscopy, inductively coupled plasma optical-emission spectrometry (ICP-OES) and circular dichroism study. All pre and post-degradation samples were further analyzed by TCS-PC. We observed that, TCS-PC can identify the differences between the initial and post degradation samples in very less time with promising discrimination power across the different injectable formulation types. Thus TCS-PC can be used as a fast and promising stability or sameness evaluation tool for different injectable drug products.

ß-sitosterol Protects against Aluminium Chloride-mediated Neurotoxicity.

OBJECTIVE: The objective of this study is to investigate the neuroprotective effects of ß- sitosterol using the AlCl3 model of Alzheimer's Disease. METHODS: AlCl3 model was used to study cognition decline and behavioral impairments in C57BL/6 mice. Animals were randomly assigned into 4 groups with the following treatments: Group 1 received normal saline for 21 days, Group 2 received AlCl3 (10 mg/kg) for 14 days; Group 3 received AlCl3(10 mg/kg) for 14 days + ß-sitosterol (25mg/kg) for 21 days; while Group 4 was administered ß-sitosterol (25mg/kg) for 21 days. On day 22, we performed the behavioral studies using a Y maze, passive avoidance test, and novel object recognition test for all groups. Then the mice were sacrificed. The corticohippocampal region of the brain was isolated for acetylcholinesterase (AChE), acetylcholine (ACh), and GSH estimation. We conducted histopathological studies using Congo red staining to measure ß -amyloid deposition in the cortex and hippocampal region for all animal groups. RESULTS: AlCl3 successfully induced cognitive decline in mice following a 14-day induction period, as shown by significantly decreased (p < 0.001) in step-through latency, % alterations, and preference index values. These animals also exhibited a substantial decrease in ACh (p <0.001) and GSH (p < 0.001) and a rise in AChE (p < 0.001) compared to the control group. Mice administered with AlCl3 and ß-sitosterol showed significantly higher step-through latency time, % alteration time, and % preference index (p < 0.001) and higher levels of ACh, GSH, and lower levels of AChE in comparison to the AlCl3 model. AlCl3-administered animals also showed higher ß-amyloid deposition, which got significantly reduced in the ß-sitosterol treated group. CONCLUSION: AlCl3 was effectively employed to induce a cognitive deficit in mice, resulting in neurochemical changes and cognitive decline. ß -sitosterol treatment mitigated AlCl3-mediated cognitive impairment.

Pharmacological Actions and Underlying Mechanisms of Catechin: A Review.

BACKGROUND: Catechin is a phytochemical and is a major component of our daily use beverages, which has shown great potential in improving general health and fighting against several medical conditions. Clinical studies have confirmed its effectiveness in conditions ranging from acute upper respiratory tract infection, neuroprotection, to cardio-protection effects. Though most studies relate their potential to anti-oxidative action and radical scavenging action, still the mechanism of action is not clearly understood. OBJECTIVE: The present review article is focused on addressing various pharmacological actions and underlying mechanisms of catechin. Additionally, we will try to figure out the major adverse effect and success in trials with catechin and lead to a conclusion for its effectiveness. METHODS: This review article is based on the recent/ most cited papers of PubMed and Scopus databases. DESCRIPTION: Catechin can regulate Nrf2 and NFkB pathways in ways that impact oxidative stress and inflammation by influencing gene expression. Other pathways like MAPKs and COMT and receptor tyrosine kinase are also affected by catechin and EGCG that alter their action and barge the cellular activity. This review article explored the structural aspect of catechin and its different isomers and analogs. It also evaluated its various therapeutic and pharmacological arrays. CONCLUSION: Catechin and its stereo-isomers have shown their effectiveness as anti-inflammatory, anti-diabetic, anti-cancer, anti-neuroprotective, bactericidal, memory enhancer, anti-arthritis, and hepato-protective mainly through its activity to alter the pathway by NF-κB, Nrf-2, TLR4/NF-κB, COMT, and MAPKs.

Two-Pore Domain Potassium Channel in Neurological Disorders.

K2P channel is the leaky potassium channel that is critical to keep up the negative resting membrane potential for legitimate electrical conductivity of the excitable tissues. Recently, many substances and medication elements are discovered that could either straightforwardly or in a roundabout way influence the 15 distinctive K+ ion channels including TWIK, TREK, TASK, TALK, THIK, and TRESK. Opening and shutting of these channels or any adjustment in their conduct is thought to alter the pathophysiological condition of CNS. There is no document available till now to explain in detail about the molecular mechanism of agents acting on K2P channel. Accordingly, in this review we cover the current research and mechanism of action of these channels, we have also tried to mention the detailed effect of drugs and how the channel behavior changes by focusing on recent advances regarding activation and modulation of ion channels.