Some variables Affecting Preparation of Nanosuspension-based Gel of Paliperidone

Abstract

An intranasal drug delivery system offers a non-invasive, effective, reliable, direct, and alternative route to the CNS via the neural connections between the nasal mucosa and the brain. Paliperidone (PAL) is mainly used to treat schizophrenia and disorder. It’s practically insoluble in water class II with low bioavailability 28%. Therefore the aim of preparation of nano nasal suspension gel is in order to target PAL to brain via neural connections of nasal mucosa and the brain, and then enhance the uptake and bioavailability of the drug near and at the site of action. Different variables were investigated in this study, in order to recognize the best formula that aims the drug to deliver by the brain through the nasal administration.Among these variables are, polymers types soluplus®, PVP (plasdone), HPMC ,and Poloxamer 188, besides to drug-polymer ratios, and  stirring speed .The prepared suspension nano particles, were evaluated according to their particles sizes, poly dispersity index (PDI), and dissolution behavior in simultaneous nasal fluid pH 6.5.The in-vitro results of the study revealed that, lowest particle size diameter was with the drug loaded by soluplus® of (1:3), (71.28 nm), compared with PVP (plasdone) of (1:3), (146.2 nm.), Poloxamer188 of (1:3), (393.1nm.), and HPMC of (1:3), (251.2 nm.), respectively. Furthermore the poly dispersity index (PDI) demonstrates that soluplus® was the lowest (0.031), compared with PVP (0.163), Polyxamer188 (0.2428), and HPMC (0.309), respectively. While the calculated entrapment efficiency (EE) % of the all PAL prepared nano particles were ranged from 81.94% to 99.99 %. According to the particle size diameter, the formula  F6 loaded by soluplus® of (1:3), was chosen for dissolution behavior of PAL in simultaneous nasal fluid pH 6.5, it gave 98% drug released, and estimated time for 50%, and 75% PAL  released at  40.3 and 73.2 minutes,  respectively