IN VITRO PERMEABILITY STUDY OF NASAL MEDICINAL PRODUCT FOR SYSTEMIC ACTION

Abstract

For systemic medicinal products bioavailability is a fundamental characteristic that determines their efficacy and onset of action. Biopharmaceutical parameters of nasal preparations (physicochemical properties of the active substance such as membrane permeability, solubility, lipophilicity, pKa, polymorphic state, type of finished dosage form, pH, osmolarity, composition and characteristics of excipients), affecting bioavailability, are variable and controllable within pharmaceutical development. Besides the use of components that affect enzymatic activity, mucoadhesion and effective con-tact time, mucociliary clearance and viscosity of mucous secretion, changing the rate and degree of absorption of the active substance is possible by modulation of tight junctions and paracellular transport. These processes can be particularly determined by the osmolarity of the dosage form and the use of permeation enhancers. Taking into account the portfolio of excipients available to scientists used in a wide range of concentrations, and, in addi-tion, the requirements of the target product profile in terms of safety and pharmacokinetic parameters, as well as regulatory recommendations for jus-tification of the composition within pharmaceutical development, with particular emphasis on the selection of functional components and the concen-trations used, it is important to have relevant and reliable screening tools when formulating a drug product. Due to the absence of standard bioavailabil-ity assessment methods for nasal preparations, literature review was conducted and methodology of in vitro permeability study for of nasal medicinal products for systemic action with the use of artificial membranes as well as cell line RPMI 2650 of human nasal epithelium is developed. The use of such sufficiently homogeneous barrier films allows to minimize the variability of test conditions. Permeation study of developed compositions of an-timigraine medicinal product is conducted. The results obtained provide evidence of their qualitative compliance and allow to recommend laboratory permeability study on cellulose membranes for the selection and justification of the composition of pharmaceutical compositions. Bioavailability is a fundamental characteristic of pharmaceutical products for systemic action, which defines efficacy and speed of action. Permeability through biological membranes is defined not only by the properties of active component but also by the particulars of formulation. Due to the absence of standard bioavailability assessment methods for nasal preparations, literature review was conducted and methodology of in vitro permeability study for of nasal medicinal products for systemic action with the use of artificial membranes as well as cell line RPMI 2650 is developed. Permeation study of developed compositions of antimigraine medicinal product is conducted. The results obtained provide evidence of their qualitative compliance and allow to recommend laboratory permeability study on cellulose membranes as a screening tool in pharmaceutical development.