Carbamazepine uptake into rat brain following intra-olfactory transport

Abstract

Targeting the brain via nasal administration of drugs has been studied frequently over the last few years. In this study, a suitable gel formulation was designed to provide the absorption of a highly lipophilic drug through nasal mucosa. For this purpose, carbamazepine was chosen as the model drug. Hypromellose and Carbopol were used as mucoadhesive polymers in the formulation to increase the residence time of the gel on the mucosa. The objective of this study was to confirm the existence of a transport pathway for a drug (carbamazepine) to the brain directly from the nasal cavity, by comparing the concentration of drug in the brain after intranasal (i.n.), intravenous (i.v.), and oral (p.o.) administration. A statistically significant high level of the drug was found in the brain following intranasal administration compared with the intravenous and oral routes. These findings suggested the existence of a direct transport pathway for carbamazepine from the nasal cavity to the brain. This pathway may represent a new delivery route to the brain and central nervous system of such drugs which are needed in high and rapid concentration in the brain, especially in emergencies.

Microemulsion-based drug delivery system for transnasal delivery of Carbamazepine: preliminary brain-targeting study

“…It is characterized by slow and irregular gastrointestinal absorption. Reportedly, it has an oral bioavailability of less than 50% (Barakat et al, 2006).…”

Preparation and in vitro/ex vivo evaluation of nanoemulsion for transnasal delivery of paliperidone

“…The results of stability studies (Table 5) showed that there are negligible changes in the parameters such as drug content, % transmittance, of PALI loaded NE and PALI loaded MNE after 6 months of storage, thus substantiating the stability of formulation for 6 months (Barakat et al 2006;Jadhav et al 2011;Karasulu et al 2008;Sharma et al 2009). …”

“…Polycarbophil form easily modified networks, is a non-irritant, non-toxic and considered safe for use by FDA. Thus, polycarbophil was selected as mucoadhesive polymer and incorporated in optimized NE formulations (PNE4, PNE5 and PNE6) at 0.5 % w/v concentration (Barakat et al 2006;Karasulu et al 2008;Kumar et al 2009) to obtain PALI loaded mucoadhesive NE formulations (PMNE4, PMNE5 and PMNE6). Characterization parameters for optimized PALI mucoadhesive NEs are shown in Table 3.…”

“…4, and the calculated diffusion coefficients are tabulated in Table 4 along with the regression coefficients (r 2 ) for first-order, Higuchi, and zero-order modeling of the diffusion profiles for each formulation (Barakat et al 2006). PALI show better diffusion from PMNE6 as compared to PMNE5, PMNE4 and PS through sheep nasal mucosa after 4 h (p \ 0.05).…”

“…5c), which substantiated the safety of the excipients used in the formulation. Therefore, formulation components can be considered as biocompatible, and may not induce serious histological changes in the nasal mucosa upon prolong use (Barakat et al 2006;Jadhav et al 2011;Karasulu et al 2008;Sharma et al 2009). …”