Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil

Abstract

Donepezil (DPZ) is widely used in the treatment of Alzheimer’s disease in tablet form for oral administration. The pharmacological efficacy of this drug can be enhanced by the use of intranasal administration because this route makes bypassing the blood–brain barrier (BBB) possible. The aim of this study was to develop a nanoemulsion (NE) as well as a nanoemulsion with a combination of bioadhesion and penetration enhancing properties (PNE) in order to facilitate the transport of DPZ from nose-to-brain. Composition of NE was established using three pseudo-ternary diagrams and PNE was developed by incorporating Pluronic F-127 to the aqueous phase. Parameters such as physical properties, stability, in vitro release profile, and ex vivo permeation were determined for both formulations. The tolerability was evaluated by in vitro and in vivo models. DPZ-NE and DPZ-PNE were transparent, monophasic, homogeneous, and physically stable with droplets of nanometric size and spherical shape. DPZ-NE showed Newtonian behavior whereas a shear thinning (pseudoplastic) behavior was observed for DPZ-PNE. The release profile of both formulations followed a hyperbolic kinetic. The permeation and prediction parameters were significantly higher for DPZ-PNE, suggesting the use of polymers to be an effective strategy to improve the bioadhesion and penetration of the drug through nasal mucosa, which consequently increase its bioavailability.

Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis

“…P127 gels are used as the vanguard of drug delivery systems development due to the improved therapeutic efficacy and adherence to the recipient [24]. They have been used as vehicles for various routes of administration of drugs, including oral and topical [25], intranasal [18,26], vaginal and rectal [27], ocular [28], and parenteral [29]. In this study, AmB-gel was developed with 5% of DMSO as an optimal solubilizing agent and 25% of P127 to confer thermoreversible character.…”

“…P407 is a low toxicity excipient approved by the Food and Drug Administration (FDA) [17]. Moreover, it has beneficial properties that help to promote and improve drug permeation through the skin and mucosa [18].…”

Topical Pioglitazone Nanoformulation for the Treatment of Atopic Dermatitis: Design, Characterization and Efficacy in Hairless Mouse Model

“…This can be attributed to the properties of Transcutol-P (polar solvent) and Capryol 90 (non-polar solvents), whose combination in the formulation could result in synergetic skin penetration enhancement due to the fact that Transcutol-P increases drug solubility in the stratum corneum (SC), whereas Capryol 90 favors the diffusion of drug in the SC [30]. Additionally, Pluronic F127 enhances the diffusion ability of drug thanks to its amphiphilic structure which allows it to act as a surfactant and interact with biological membranes [31,32].…”

<p>Primary Studies on Construction and Evaluation of Ion-Sensitive in situ Gel Loaded with Paeonol-Solid Lipid Nanoparticles for Intranasal Drug Delivery</p>

“…7 The main pathways of nose-brain transport are nerve pathway, mucous pathway, blood circulation pathway and lymphoid pathway. 8,9 The neural pathway mainly based on olfactory nerve transmission is also called direct pathway, which can transport drugs directly from the olfactory area to the brain region with high transmission efficiency. 10 The secretion of nasal mucus, the nasal clearance caused by the rapid swinging of nasal cilia and the permeability of nasal mucosa are the main limitations of nasal administration.…”