Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Fexofenadine.

In this monograph, the potential use of methods based on the Biopharmaceutics Classification System (BCS) framework to evaluate the bioequivalence of solid immediate-release (IR) oral dosage forms containing fexofenadine hydrochloride as a substitute for a pharmacokinetic study in human volunteers is investigated. We assessed the solubility, permeability, dissolution, pharmacokinetics, pharmacodynamics, therapeutic index, bioavailability, drug-excipient interaction, and other properties using BCS recommendations from the ICH, FDA and EMA. The findings unequivocally support fexofenadine's classification to BCS Class IV as it is neither highly soluble nor highly permeable. Further impeding the approval of generic equivalents through the BCS-biowaiver pathway is the reference product's inability to release ≥ 85 % of the drug substance within 30 min in pH 1.2 and pH 4.5 media. According to ICH rules, BCS class IV drugs do not qualify for waiving clinical bioequivalence studies based on the BCS, even though fexofenadine has behaved more like a BCS class I/III than a class IV molecule in pharmacokinetic studies to date and has a wide therapeutic index.

Ubiquitous Neural Cell Adhesion Molecule (NCAM): Potential Mechanism and Valorisation in Cancer Pathophysiology, Drug Targeting and Molecular Transductions.

Neural cell adhesion molecule, an integrated molecule of immunoglobulin protein superfamily involved in cell-cell adhesion, undergoes various structural modifications through numerous temporal-spatial regulations that generously alter their expressions on cell surfaces. These varied expression patterns are mostly envisioned in the morphogenesis and innervations of different human organs and systems. The considerable role of NCAM in neurite growth, brain development and etc. and its altered expression of NCAM in proliferating tumour cells and metastasis of various human melanomas clearly substantiate its appropriateness as a cell surface marker for diagnosis and potential target for several therapeutic moieties. This characteristic behaviour of NCAM is confined to its novel biochemistry, structural properties, signalling interactions and polysialylation. In particular, the characteristic expressions of NCAM are mainly attributed by its polysialylation, a post-translational modification that attaches polysialyl groups to the NCAM. The altered expression of NCAM on cell surface develops curiosity amidst pharmaceutical scientists, which drives them to understand its role of such expressions in various human melanomas and to elucidate the promising therapeutic strategies that are currently available to target NCAM appositely. Therefore, this review article is articulated with an insight on the altered expressions of NCAM, the clinical significances and the consequences of such atypical expression patterns in various human organs and systems.

The multifunctional synergistic effect of chitosan on simvastatin loaded nanoparticulate drug delivery system.

The present study reported design and evaluation of nanoformulations of Simvastatin using different polymers. The study emphasizes upon the synergistic activity of the drug and the polymers owing to the reported anti- hyperlipidemic activity of the selected polymers. Preliminary studies advocated for chitosan formulations due to the expected particle size (543±26nm) among the three polymer formulations. Four formulations (F1-F4) were prepared varying chitosan ratio. F4 demonstrated optimal characteristics (particle size - 549±23.43nm, narrow size distribution - 0.515±0.06) and qualified for further investigation. The formulation parameters modified the intrinsic properties of chitosan. Formation of low M. wt chitosan (70,000±10,000Da) enhanced swelling & mucoadhesive properties. These influenced the drug properties in which amorphization of drug increased solubility and decreased partition coefficient. This led to better absorption at intestine sustaining the drug release up to 66.18±1.26% in SIF during the in vitro study. Better absorption was confirmed by reduction in lipid profile with several fold reduced dose in mouse model. The in vitro bile binding property of chitosan in formulation demonstrated the enhancement of hypolipidemic activity of Simvastatin. The outcomes of the study showed a successful preparation of optimum nanoformulations and also revealed possible synergistic functionalities of chitosan and the Simvastatin as potential hypolipidaemic modality without any toxic manifestations.