Investigation of the Absorption of Nanosized lamotrigine Containing Nasal Powder via the Nasal Cavity

Abstract

Nasal drug delivery has become a popular research field in the last years. This is not surprising since the nose possesses unique anatomical and physical properties. Via the nasal mucosa local, systemic, and directly central nerve systemic (CNS) effect is achievable. Powders have favorable physicochemical properties over liquid formulations. Lamotrigine (LAM) is an antiepileptic agent with a relatively mild side effect spectrum, but only available in tablet form on market. Reducing the particle size to the nano range can affect the bioavailability of pharmaceutical products. The aim of this article was to continue the work started, compare the in vitro properties of a nanonized lamotrigine containing nasal powder (nanoLAMpowder) and its physical mixture (PM) that were prepared by dry milling. Moreover, to study their trans-epithelial absorption to reach the blood and target the brain by axonal transport. Due to the dry milling technique, the particle size of LAM, their surface and also their structure changed that led to higher in vitro dissolution and permeability rate. The results of the in vivo tests showed that the axonal transport of the drug was assumable by both intranasal formulations because the drug was present in the brain within a really short time, but the LAM from the nanoLAMpowder liberated even faster.

Spray Dried Levodopa-Doped Powder Potentially for Intranasal Delivery

“…Nasal administration offers a non-invasive pathway to delivery drugs for treating both local and systemic diseases, with several advantages of bypassing the blood-brain barrier, avoiding hepatic first-pass elimination, and reducing side effects [ 1 , 2 , 3 ]. Particularly aiming at central nervous system (CNS) diseases, including schizophrenia, migraines, Parkinson’s, etc., intranasal drug delivery via the olfactory and trigeminal routes directly to the brain is capable of providing much more effective drug concentration at lower doses and reduced risk for adverse reactions [ 4 , 5 , 6 , 7 ].…”

Comparison of Modern In Vitro Permeability Methods with the Aim of Investigation Nasal Dosage Forms

“…Furthermore, the usage of mucoadhesive additives allows the delivery of nanosized drugs intranasally to overcome the limitations of the particle size requirements for nasal formulations. Based on our previous experience, it can be concluded that the bioavailability of an active pharmaceutical ingredient is increased by decreasing its particle size [18,19].…”

Flurbiprofen sodium microparticles and soft pellets for nose-to-brain delivery: Serum and brain levels in rats after nasal insufflation

“…In particular, drug transport to brain across the nasal epithelium could be further improved by using nasal powders (Ambrus et al, 2020;Rassu et al, 2018;Tanaka et al, 2016). The solid particle dissolution and drug release in the fluid lining the nasal epithelium sustain the drug passive diffusion rate, owing to the saturation concentration in contact with the tissue (Colombo et al, 2016;Giuliani et al, 2018;Pozzoli et al, 2017).…”