Molecular Docking and ADMET Analysis Strategy-Based Stability Indicating RP-HPLC-PDA Method Development and Validation of Toremifene.

BACKGROUND: The purpose of this research is to develop an analytical method and validate it according to ICH guidelines for the estimation of Toremifene by RP-HPLC-PDA with molecular docking and ADMET analysis. From molecular docking, it came to know the receptor affinity specifically to estrogen receptors (ERα and ERß), which are responsible for cancer therapy. ADMET analyses secure its therapeutic potential as well safety of the drug. METHODS: An isocratic method has developed by RP-HPLC-PDA (AGILENT 1100) with symmetry of 100 mm x 4.6 mm x 5 µm particle size C18 column and optimise mobile phase is methanol: 0.1% OPA (orthophosphoric acid) water ratio of 43:57% v/v. Under different conditions like acidic, alkaline, oxidative, and neutral environments, toremifene was tested for degradation. RESULTS: The developed method is validated in accordance with ICH guidelines. A calibration curve with an r2 value of 0.9987 has been prepared across the range of 10 to 50 µg/ml with five standard dilutions. The retention time of the drug is 5.575 minutes. The validation results are system suitability (%RSD-0.76), inter-day precision (%RSD 0.14-0.29), intraday precision (%RSD 0.08-0.34), accuracy (%RSD 0.16-0.96), and robustness (%RSD 0.16-0.35). In different intended conditions, four peaks are in 1 N HCl, two peaks in 1 N NaOH, three peaks in 10% H2O2 (1hr), and one peak in neutral. CONCLUSION: Toremifene, a Selective Estrogen Receptor Modulator (SERM), Drug pharmacokinetic properties and receptor binding affinity results are helpful in designing the analytical method. Developing the RP-HPLC-PDA method is found to be novel, simple and precise. It could be used for testing toremifene in bulk and pharmaceutical tablet dosage forms in quality control, as well as stability tests.

Approaches for Ear-targeted Delivery Systems in Neurosensory Disorders to avoid Chronic Hearing Loss Mediated Neurological Diseases.

BACKGROUND AND OBJECTIVE: Hearing loss is a common audio-vestibular-related neurosensory disability of inner ears, in which patients exhibit clinical symptoms of dizziness, gait unsteadiness, and oscillopsia, at an initial stage. While, if such disorders are untreated for a prolonged duration then the progression of disease into a chronic state significantly decreases GABA level as well as an alteration in the neurotransmission of CNS systems. Hence, to control the progression of disease into a chronic approaches for timely and targeted delivery of the drugs at the site of action in the ear is now attracting the interest of neurologists for effective and safe treatment of such disorders. Among delivery systems, owing to small dimension, better penetration, rate-controlled release, higher bioavailability; nanocarriers are preferred to overcome delivery barriers, improvement in residence time, and enhanced the performance of loaded drugs. Subsequently, these carriers also stabilize encapsulated drugs while also provide an opportunity to modify the surface of carriers to favor guided direction for site-specific targeting. Contrary to this; conventional routes of drug delivery such as oral, intravenous, and intramuscular are poorer in performance because of inadequate blood supply to the inner ear and limited penetration of blood-inner ear barrier. CONCLUSION: This review summarized novel aspects of non-invasive and biocompatible nanoparticles- based approaches for targeted delivery of drugs into the cochlea of the ear to reduce the rate, and extent of the emergence of any hearing loss mediated neurological disorders.