Synthesis of pH-Sensitive Cross-Linked Basil Seed Gum/Acrylic Acid Hydrogels by Free Radical Copolymerization Technique for Sustained Delivery of Captopril

The pH-sensitive polymeric matrix of basil seed gum (BSG), with two different monomers, such as acrylic acid (AA) and N, N-Methylene-bis-acrylamide (MBA), was selected to use in hydrogels preparation through a free radical copolymerization technique using potassium per sulfate (KPS) as a cross linker. BSG, AA and MBA were used in multiple ratios to investigate the polymer, monomer and initiator effects on swelling properties and release pattern of captopril. Characterization of formulated hydrogels was done by FTIR, DSC/TGA, XRD and SEM techniques to confirm the stability. The hydrogels were subjected to a variety of tests, including dynamic swelling investigations, drug loading, in vitro drug release, sol–gel analyses and rheological studies. FTIR analysis confirmed that after the polymeric reaction of BSG with the AA monomer, AA chains grafted onto the backbone of BSG. The SEM micrographs illustrated an irregular, rough, and porous form of surface. Gel content was increased by increasing the contents of polymeric gum (BSG) with monomers (AA and MBA). Acidic and basic pH effects highlighted the difference between the swelling properties with BSG and AA on increasing concentration. Kinetic modelling suggested that Korsmeyer Peppas model release pattern was followed by the drug with the non-Fickian diffusion mechanism

In Vitro/In Vivo Evaluation of Clomipramine Orodispersible Tablets for the Treatment of Depression and Obsessive-Compulsive Disorder

The first and only antidepressant drug on the market with solid proof of clinically significant serotonin and noradrenaline reuptake inhibition is clomipramine (CLP). However, significant first-pass metabolism reduces its absorption to less than 62%. It is heavily protein-bound and broadly dispersed across the body (9–25 L/kg volume of distribution). The purpose of this research was to formulate CLP orodispersible tablets that immediately enable the drug to enter the bloodstream and bypass systemic portal circulation to improve its bioavailability. A factorial design was employed using varied amounts of Plantago ovata mucilage (POM) as a natural superdisintegrant, as well as croscarmellose sodium and crospovidone as synthetic disintegrants. Their physiochemical compatibility was evaluated by FTIR, DSC/TGA, and PXRD analysis. The blend of all formulations was assessed for pre- and post-compaction parameters. The study found that tablets comprising Plantago ovata mucilage as a superdisintegrant showed a rapid in vitro disintegration time, i.e., around 8.39 s, and had an excellent dissolution profile. The anti-depressant efficacy was evaluated by an open-field test (OFT) and the forced swimming test (FST) was applied to create hopelessness and despair behavior as a model of depression in animals (Albino rats). The in vivo study revealed that the efficiency of the optimized formulation (F9) in the treatment of depression is more than the marketed available clomfranil tablet, and may be linked to its rapid disintegration and bypassing of systemic portal circulation

Imine Derivatives of Benzoxazole Attenuate High-Fat Diet-Induced Hyperlipidemia by Modulation of Lipid-Regulating Genes

Purpose: Hyperlipidemia being the prominent risk factor of cardiovascular diseases and side effects associated with the current lipid-lowering drugs have attracted the interest of scientists in the quest for new alternatives. In view of the diverse pharmacological potentials of benzoxazole (BZX) compounds, this study was designed to evaluate the antihyperlipidemic activity of imine derivatives of BZX in high-fat diet (HFD)-fed rats. Methods: Hyperlipidemia was induced in Sprague–Dawley rats by using HFD for 28 days. On the 28th day, blood samples were collected, and animals having serum triglycerides (TG) greater than 400 mg/dL and total cholesterol (TC) greater than 280 mg/dL were selected for further study. Hyperlipidemic rats were daily treated with either a vehicle or simvastatin (SIM; 20 mg/kg) or BZX compounds (10, 20, and 30 mg/kg), for 12 consecutive days. After the specified time duration, hyperlipidemic biomarkers were evaluated in the blood samples of sacrificed rats. Liver samples were collected for histopathological and mRNA analyses. Binding affinities of BZX derivatives with different targets were assessed by molecular docking. Results: The present study revealed that the BZX derivatives dose-dependently reduced the serum levels of TC, TG, low-density lipoprotein, and very low-density lipoprotein along with improvement in high-density lipoprotein levels. Similarly, all the compounds reduced HFD-induced alanine transaminase and aspartate aminotransferase levels except BZX-4. Histopathology of liver samples demonstrated mild to moderate fatty changes upon treatment with BZX-1, BZX-2, and BZX-4. The hepatic architecture of the BZX-3-treated samples was close to normal, and only mild inflammation was witnessed in these samples. Moreover, all the compounds significantly increased superoxide dismutase and glutathione levels, indicating their antioxidant potentials. Gene expression data showed that BZX-1 and BZX-3 reduced lipid levels by inhibiting HMGCR, APOB, PCSK9, SRB1, and VCAM1 and via improving PPAR-α and APOE mRNA levels. BZX-2 demonstrated its antihyperlipidemic effects mainly due to inhibition of APOB, while BZX-4-mediated effects appeared to be due to attenuation of APOB, PCSK9, and SRB1. BZX derivatives displayed strong binding affinities with HMGCR, APOB, and VCAM1, which suggested that some of the interactions might be required for inhibition of these target proteins. Conclusions: Based on the current findings, it can be concluded that BZX derivatives exert their antihyperlipidemic effects via modulation of multiple lipid-regulating genes