National Institute of Pharmaceutical Education and Research, Hajipur (NIPER Hajipur) is a public pharmaceutical education and research university located in Hajipur, Bihar, India. Established in 2007, it is one of the seven National Institutes of Pharmaceutical Education and Research (NIPERs) under India's Ministry of Chemicals and Fertilizers. The institute offers Post Graduate degree in pharmaceutical sciences. Like all other NIPERs, it has the Institute of National Importance status.
Aim: To Discover novel PTP1B inhibitors by high-throughput virtual screening Background: Type 2 Diabetes is a significant global health concern. According to projections, the estimated number of individuals affected by the condition will reach 578 million by the year 2030 and is expected to further increase to 700 million deaths by 2045. Protein Tyrosine Phosphatase 1B is an enzymatic protein that has a negative regulatory effect on the pathways involved in insulin signaling. This regulatory action ultimately results in the development of insulin resistance and the subsequent elevation of glucose levels in the bloodstream. The proper functioning of insulin signaling is essential for maintaining glucose homeostasis, whereas the disruption of insulin signaling can result in the development of type 2 diabetes. Consequently, we sought to utilize PTP1B as a drug target in this investigation. Objective: The purpose of our study was to identify novel PTP1B inhibitors as a potential treatment for managing type 2 diabetes. Methods: To discover potent PTP1B inhibitors, we have screened the Maybridge HitDiscover database by SBVS. Top hits have been passed based on various drug-likeness rules, toxicity predictions, ADME assessment, Consensus Molecular docking, DFT, and 300 ns MD Simulations. Results: Two compounds have been identified with strong binding affinity at the active site of PTP1B along with drug-like properties, efficient ADME, low toxicity, and high stability. Conclusion: The identified molecules could potentially manage T2DM effectively by inhibiting PTP1B, providing a promising avenue for therapeutic strategies.
Reverse engineering (RE) of reference-listed drugs (RLD) plays a major role in developing cost- and time-effective, high-quality generic products for affordable therapies without compromising healthcare quality. The present study attempted to develop the RE protocol using Pentasa™- Mesalamine prolonged-release granules (PRGs) as a model drug product. RE of three different RLD lots was carried out using analytical techniques such as UV spectroscopy, moisture content using water activity and IR moisture balance, High Performance Liquid Chromatography – Reverse Phase (HPLC) for assay, Fourier-Transform Infrared spectroscopy (FT-IR), Raman Spectroscopy- 532 nm (RS- 532), Proton Nuclear Magnetic Resonance Spectroscopy – 500 MHz (NMR) for drug excipient compatibility/interaction studies, Optical and Scanning Electron Microscopy (SEM) for surface morphology, Raman Chemical Imaging (RCI) and Focal Plane Array-FTIR (FPA-FTIR) chemical imaging for drug and excipient distribution in intact granules, surface area and porosity by BET, thermal analysis by DSC, crystallinity using PXRD, metallic impurities using LC Inductively Coupled Plasma Mass Spectrometry (LC ICP-MS) and particle size by laser diffraction, Head Space Gas Chromatography-Mass spectrometry (HS GC–MS) for residual solvents, size exclusion chromatography for molecular weight determination of PVP and ethyl cellulose, texture analysis for deformation studies, packaging evaluation, and in vitro multimedia dissolution using validated USP method. The resulting data was useful in finalising qualitative and quantitative compositions, selecting the technical grade of excipients, understanding the innovator manufacturing process, establishing QTPP, FMEA, and packaging material selection. This work shall serve as a model protocol for RE of RLD formulation for developing complex generic products.
Bile salt-polymer ternary solid dispersion (SD) is a new approach incorporating the bile salt in binary polymeric SD. Bile salts, being endogenous surface-active molecules, have been reported to enhance the solubilization and inhibit crystallization of poorly water-soluble drugs. Thus, the current investigation moves a step forward and aims to develop bile salt-polymer ternary SD of the model drug, Mebendazole (MBZ), to enhance its biopharmaceutical performance. We explored the role of sodium cholate (NaC; bile salt) and hydroxypropyl methylcellulose acetate succinate high fine (HPMCAS HF; polymer), in solubilization and supersaturation maintenance of MBZ, respectively, through saturation solubility and supersaturation assay. The optimized ternary SD (MBZ:NaC:HPMCAS HF) was amorphous in nature as confirmed by P-XRD and PLM, and exhibited strong drug-bile salt-polymer interactions, confirmed by spectroscopic techniques. Moreover, the ternary SD showed enhancement in apparent solubility and dissolution of MBZ by similar to 11 and 10-fold, respectively, and exhibited an increase in C-max (2.71-fold) and AUC(0-24) (1.78-fold) in the pharmacokinetic study. Further, pharmacodynamic study revealed enhancement in the anthelmintic activity of MBZ by ternary SD in Trichuris muris-infected mice. Ternary SD at a 200 mg/kg dose showed similar to 96 % worm burden reduction and almost equivalent reduction (similar to 85 %) at its lower dose (100 mg/kg) to that of crystalline MBZ (200 mg/kg). This enables the possibility of dose reduction of MBZ with its more manageable dosage regimen and fewer side effects. The findings suggested that the incorporation of bile salt in polymeric SD offered an alternative formulation for MBZ to ameliorate its dissolution, oral bioavailability, and in vivo efficacy.
Microorganisms use host microRNAs (miRNAs) to evade immune responses and establish chronic infections. miRNAs, small non-coding RNAs, regulate gene expression post-transcriptionally, influencing host-pathogen interactions. Mycobacterium tuberculosis and other intracellular pathogens evade host immunity, promoting survival within macrophages. Dysregulated miRNA profiles in TB patients linked with disease progression, immune modulation, and treatment outcomes, serving as potential biomarkers. Biosensor technology emerged as a powerful tool for rapid and sensitive detection. MicroRNA-based diagnostics offers a promising approach for precision medicine in tuberculosis (TB) management. This review highlights the dual role of miRNAs in tuberculosis by elucidating their mechanistic contribution to host immune evasion and evaluating their potential as diagnostic biomarkers through emerging biosensor technologies. Despite these promising advances, challenges such as variability in miRNA expression across populations and the need for large-scale clinical validation remain, highlighting the importance of further research to translate miRNA-based diagnostics into routine clinical practice.
The dissolution behaviour of sub-micronized nanocrystals, especially for poorly soluble drugs, is quite unpredictable. Mesalamine (MES) is a high-dose, poorly soluble drug with two pKa and four ionic forms. The fabrication of sub-micronized nanocrystals reduces the dose, pill burden, and improves the therapeutic adherence. The present study investigates the dissolution behaviour of sub-micronized mesalamine (SMES), also known as nanocrystals, micronized crystals, suspension, and tablets, using different dissolution methods and the USP dissolution apparatus. The method parameters, including the choice of apparatus, hydrodynamics, buffer capacity, pH, and volume of the media, were optimized to achieve the optimal dissolution method for discriminating particle sizes. The particle size discriminatory powder dissolution method (method 5) was developed using the 1 mm beads in the USP Type I apparatus. The dissolution efficacy of MES and SMES was found to be 31.2
