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

Abstract

Paroxetine (PX) is the most potent serotonin reuptake inhibitor utilized in depression and anxiety treatment. It has drawbacks, such as having a very bitter taste, low water solubility, and undergoing extensive first pass metabolism, leading to poor oral bioavailability (<50%). This work aimed to develop and optimize palatable oral fast-dissolving films (OFDFs) loaded with a paroxetine nanosuspension. A PX nanosuspension was prepared to increase the PX solubility and permeability via the buccal mucosa. The OFDFs could increase PX bioavailability due to their rapid dissolution in saliva, without needing water, and the rapid absorption of the loaded drug through the buccal mucosa, thus decreasing the PX metabolism in the liver. OFDFs also offer better convenience to patients with mental illness, as well as pediatric, elderly, and developmentally disabled patients. The PX nanosuspension was characterized by particle size, poly dispersity index, and zeta potential. Twelve OFDFs were formulated using a solvent casting technique. A 22 × 31 full factorial design was applied to choose the optimized OFDF, utilizing Design-Expert® software (Stat-Ease Inc., Minneapolis, MN, USA). The optimized OFDF (F1) had a 3.89 ± 0.19 Mpa tensile strength, 53.08 ± 1.28% elongation%, 8.12 ± 0.13 MPa Young’s modulus, 17.09 ± 1.30 s disintegration time, and 96.02 ± 3.46% PX dissolved after 10 min. This optimized OFDF was subjected to in vitro dissolution, ex vivo permeation, stability, and palatability studies. The permeation study, using chicken buccal pouch, revealed increased drug permeation from the optimized OFDF; with a more than three-fold increase in permeation over the pure drug. The relative bioavailability of the optimized OFDF in comparison with the market tablet was estimated clinically in healthy human volunteers and was found to be 178.43%. These findings confirmed the success of the OFDFs loaded with PX nanosuspension for increasing PX bioavailability.

Development and Characterizations of Pullulan and Maltodextrin-Based Oral Fast-Dissolving Films Employing a Box–Behnken Experimental Design

“…The film was dissolved in 5 mL of deionized water, and the pH was recorded with a digital pH meter (model: Vision Plus pH 6175, JENCO, San Diego, CA, USA) [ 27 ]. This study was repeated in triplicate.…”

Formulation and Characterization of Nicotine Microemulsion-Loaded Fast-Dissolving Films for Smoking Cessation

“…It was found that incorporating Tween 80 into the film can increase drug permeation. Since the surfactant created an elastic function that loosened or fluidized the mucosal membrane lipid bilayer and allowed the drug to incorporate into deeper layers of the biological membrane, leading to an increase in the drug permeability through the buccal mucosa [ 23 ]. No previous study used PEG-40H in oral film formulations, however, the recent study resulted that PEG-40H yielded a film effect that was similar to that of using P-80 as a surfactant.…”

Evaluation of Usnea barbata (L.) Weber ex F.H. Wigg Extract in Canola Oil Loaded in Bioadhesive Oral Films for Potential Applications in Oral Cavity Infections and Malignancy

“…It influences the film’s friability; however, both formulations (F-UBO and R) display good resistance. The moisture can be due to the solvent system used in the formulation or to the ingredients’ hygroscopic properties, especially the plasticizer ones [ 82 ]. PEG 400 presents high hygroscopicity due to its hydrophilic hydroxyl groups interacting with water [ 83 ], providing more sites for interactions and leading to moisture retention in the films.…”