In vitro formulation optimization of intranasal galantamine leading to enhanced bioavailability and reduced emetic response in vivo.

The purpose of the current investigation was to optimize an intranasal (IN) galantamine (an acetylcholinesterase inhibitor used for treatment of Alzheimer's disease) formulation using an in vitro tissue model, to correlate those results to in vivo bioavailability, and to compare emetic response to oral dosing. A design-of-experiments (DOE) based formulation screening employing an in vitro tissue model of human nasal epithelium was used to assess drug permeability, tight junction modulation, and cellular toxicity. In vivo studies in rats compared pharmacokinetic (PK) profiles of different formulations dosed intranasally.

Therapeutic utility of a novel tight junction modulating peptide for enhancing intranasal drug delivery.

Previously, a novel tight junction modulating (TJM) peptide was described affording a transient, reversible lowering of transepithelial electrical resistance (TER) in an in vitro model of nasal epithelial tissue. In the current report, this peptide has been further evaluated for utility as an excipient in transepithelial drug formulations. Chemical stability was optimal at neutral to acidic pH when stored at or below room temperature, conditions relevant to therapeutic formulations.

Lower mean weight after 14 days intravenous administration peptide YY3-36 (PYY3-36) in rabbits.

Objective: Endogenous peptide YY(3-36) (PYY(3-36)) is associated with postprandial regulation of appetite. We investigated the safety and effectiveness of peripherally administered synthetic human PYY(3-36) for 14 days in New Zealand white rabbits. Weight gain and food consumption were assessed and pharmacokinetics and toxicity characterized.

Development of a novel high-concentration galantamine formulation suitable for intranasal delivery.

The goal of the current study was to develop an intranasal (IN) formulation of the acetylcholinesterase inhibitor galantamine, an important therapeutic for treating Alzheimer's disease. To allow for delivering a therapeutically relevant dose, it was necessary to greatly enhance drug solubility. Various approaches were examined to this end, including adding co-solvents, cyclodextrins, and counterion exchange.