Showing papers by "Kadi Sarva Vishwavidyalaya published in 2019"

Mechanochemical synthesis of brexpiprazole cocrystals to improve its pharmaceutical attributes

Abstract: In the present study, cocrystallization of a new piprazole analogue drug, brexpiprazole (BREX), with coformers such as succinic acid and catechol was carried out using ball milling to address the poor solubility and dissolution rate of the molecule. Before initiating cocrystallization, several ball milling process parameters, including milling time, ball size and RPM were optimized to obtain the cocrystals with the highest purity and yield. The cocrystals generated using the optimized ball milling process were characterized using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), hot stage microscopy, Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. Equilibrium solubility and dissolution studies on the cocrystals were performed in 0.05 M acetate buffer, pH 4.3. Nearly 2.5 fold enhancements in the equilibrium solubility and dissolution rate have been observed with the cocrystals compared to plain BREX and its physical mixture with the coformers.

New Promises to Cure Cancer and Other Genetic Diseases/Disorders: Epi-drugs Through Epigenetics

Abstract: All the heritable alterations in gene expression and chromatin structure due to chemical modifications that do not involve changes in the primary gene nucleotide sequence are referred to as epigenetics. DNA methylation, histone modifications, and non-coding RNAs are distinct types of epigenetic inheritance. Epigenetic patterns have been linked to the developmental stages, environmental exposure, and diet. Therapeutic strategies are now being developed to target human diseases such as cancer with mutations in epigenetic regulatory genes using specific inhibitors. Within the past two decades, seven epigenetic drugs have received regulatory approval and many others show their candidature in clinical trials. The current article represents a review of epigenetic heritance, diseases connected with epigenetic alterations and regulatory approved epigenetic drugs as future medicines.

Brexpiprazole–catechol cocrystal: structure elucidation, excipient compatibility and stability

Abstract: Brexpiprazole (BREX) is a well known drug used in the treatment of atypical psychotic disorder. BREX is known to exhibit photo-instability on granulation with the most commonly used binder, polyvinylpyrrolidone (PVP), in wet granulation. The present study reports a cocrystal of BREX with catechol (CAT), its structure elucidation using single crystal X-ray diffraction and its processability. The brexpiprazole–catechol (BRC) cocrystal crystallizes in the P21/c space group. Structural analysis of BRC shows R22(8) between BREX and CAT through weak C–H⋯O and strong O–H⋯O hydrogen bond interactions. BREX is marketed in tablet dosage form. The compatibility of the generated cocrystal in the presence of several excipients was evaluated using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The cocrystal remained stable, with no signs of incompatibility during the excipient compatibility study. Additionally, the cocrystal and plain BREX granulated with PVP as a binder and the chemical stability of the granules were investigated. Plain BREX showed oxidative degradation and formation of N-oxide degradation products under stability conditions within 7 days. More importantly, the BRC cocrystal displayed superior stability against stability conditions because the reactive site in the piperazine ring of the BREX moiety was blocked in the BRC cocrystal due to the hydrogen bond between the drug and co-former.

Zika Virus Targeting by Screening Inhibitors against NS2B/NS3 Protease.

Abstract: Zika flavivirus is suspected to cause Guillain-Barre syndrome in adults and microcephaly, along with other congenital abnormalities in infants. Presently, no vaccines or therapeutics are available. Here, we report novel compounds identified by high-throughput virtual screening of Maybridge chemical database and molecular docking studies. We selected viral enzyme NS2B/NS3 serine protease as the therapeutic target because of its important role in viral replication. We selected seven potential compounds as antiviral drug candidates because of their high GOLD fitness score, high AutoDock Vina score, or X-Score binding energy and analyzed the strength of molecular interactions between the active site amino acids and selected compounds. Our study also provides a foundation for similar studies for the search of novel therapeutics against Zika virus.

Development and Validation of a High-Performance Thin-Layer Chromatographic (HPTLC) Method for Simultaneous Quantification of Reserpine, Atropine, and Piperine in Sarpagandha Ghanvati, a Classical Ayurvedic Preparation.

Abstract: Background: Anxiety disorders are the most common of emotional disorders, affecting more than 20 million people annually. Sarpagandha Ghanvati is a classical Ayurvedic polyherbal formulation prescribed in conditions of insomnia, hysteria, and is used as an anxiolytic agent. Standardization and quality control are the two major issues that need to be addressed for herbal formulations, especially those containing multiple herbal ingredients. Objective: An HPTLC method was developed for the simultaneous quantification of reserpine, atropine, and piperine from Sarpagandha Ghanvati containing Rauwolfia serpentine (root), Hyoscyamus niger (seed), and Piper longum (root and stem). Methods: The marker compounds were effectively resolved on a silica gel G TLC plate using toluene-ethyl acetate-diethyl amine (7+2+1, v/v) as the mobile phase. The detected wavelengths for reserpine, atropine, and piperine were 269, 220, and 254 nm, respectively. The method was validated as per the International Conference on Harmonization guidelines. Results: R. serpentine roots contained 0.82% w/w of reserpine. Atropine content in the seeds of H. niger was found to be 0.004% w/w, whereas P. longum roots were found to contain 0.508% of piperine. The method was found to be accurate, which was evident from 98.93, 99.46, and 99.10% recovery of reserpine, atropine, and piperine, respectively, when the respective herbs were spiked with them. By the developed HPTLC method, 1.0 g of Sarpagandha Ghanvati was found to contain 4.94, 0.049, and 0.318 mg of reserpine, atropine, and piperine, respectively. The recoveries of these three markers from the formulation were found to be 90.32, 92.45, and 89.97%, respectively. Conclusions: The developed method can be successfully used for simultaneous estimation of these marker compounds and for the quality control of the classical Ayurvedic formulation Sarpagandha Ghanvati. Highlights: This works describes effects of extraction solvents on the quantities of marker compounds in the formulations. It also suggests a simple and reliable HPTLC method for simultaneous quantification of three different marker compounds from a poly-herbal formulation.