Effect of surfactants and pH on naltrexone (NTX) permeation across buccal mucosa

Abstract

The objective of this pre-formulation study was to systematically investigate the effects of two surfactants (Brij 58® and Tween 80®) and change in solution pH on in vitro permeation of naltrexone HCl (NTX-HCl) across tissue engineered human buccal mucosa. For the study, 10 mg/mL solutions of Tween 80® (0.1 and 1 % w/v) and Brij 58® (1 % w/v) were prepared in standard artificial saliva buffer solution (pH 6.8). For studying pH effects, solution pH was adjusted to either 7.5 or 8.2. As controls, three concentrations of NTX-HCl (2.5, 10 and 25 mg/mL) were prepared. Using NTX standard solution (10mg/ml; pH 6.8), the permeation was observed between in vitro human and ex vivo porcine mucosa. It was observed that Brij 58® increased the permeation rates of NTX significantly. The flux of 10mg/ml solution (pH 6.8) increased from 1.9 ± 0.6 (×102) to 13.9 ± 2.2 (×102) μg/cm2/h (approximately 6 fold) in presence of 1% Brij 58®. Increasing pH of NTX-HCl solution was found to increase the drug flux from 1.9 ± 0.6 (×102) (pH 6.8) to 3.0 ± 0.6 (×102) (pH 7.4) and 8.0 ± 3.5 (×102) (pH 8.2) μg/cm2/h respectively. Histological analyses exhibited no tissue damage due to exposure of buccal tissue to Brij 58®. The mean permeability coefficients (Kp) for 2.5, 10 and 25 mg/mL solutions of NTX-HCl (pH 6.8) were 5.0 (×10−2), 1.8 (×10−2) and 3.2 (×10−2) cm/h respectively, consistent with data from published literature sources. Increase of NTX flux observed with 1% Brij 58® solution may be due to the effects of ATP. Increase in flux and the shortening of lag time observed by increasing in solution pH confirmed earlier finding that distribution coefficient (log D) of NTX is significantly affected by small increments in pH value and therefore plays an important role in NTX permeation by allowing faster diffusion across tissue engineered human buccal membranes.

Improving Drug Delivery on Candida Albicans Using Geraniol Nanoemulsion

“…The reduced MIC of GE-NE can be explained by the presence of cholesterol in the composition of the NE system [25,58], allowing interaction with the ergosterol present in the fungal cell membrane, inducing the release of GE directly on the target. In addition, surfactants can cause the breakdown of lipids in the biological membrane, leading to a reduction in the structure of the membrane barrier and causing an increase in the permeation of active compounds [59,60].…”

Biopolymer Drug Delivery Systems for Oromucosal Application: Recent Trends in Pharmaceutical R&D

“…and mucoadhesive biopolymers such as chitosan, sodium carboxymethyl cellulose (CMC), etc. [92][93][94][95][96].…”

Formulation and Development of Oral Fast-Dissolving Films Loaded with Nanosuspension to Augment Paroxetine Bioavailability: In Vitro Characterization, Ex Vivo Permeation, and Pharmacokinetic Evaluation in Healthy Human Volunteers

“…Second, the rapid disintegration of the optimized OFDF resulted in rapid absorption through the buccal mucosa and the prevention of large amounts of PX being metabolized in liver, achieving a higher bioavailability [53]. Third, the incorporation of tween 80 in the film formulation could have led to increased PX particle permeability at the absorption sites, which boosted the absorbed fraction of PX [17,21,27].…”

“…Tween 80 was incorporated as a wetting agent to accelerate the disintegration of the prepared OFDFs within seconds, releasing the loaded drug rapidly [15,16]. Moreover, it was used as a permeation enhancer to increase the PX penetration through the buccal mucosa, because of its non-ionic nature, high HLB value, and low critical micelle concentration [17]. A full factorial design (2 2 × 3 1 ) was implemented, to investigate the formulation variables affecting PX OFDFs properties, utilizing Design-Expert ® software.…”