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.

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In situ forming nanovesicular systems (IFNs) were prepared and optimized to improve Rosuvastatin calcium (RC) oral bioavailability through increasing its solubility and dissolution rate. The IFN was composed of Tween® 80 (T80), cetyl alcohol (CA), in addition to mannitol or Aerosil 200. A single simple step was adopted for preparation, then the prepared formulations were investigated by analyzing their particle size (PS), polydispersity index (PDI), Zeta potential (ZP), entrapment efficiency (EE), and flowability properties. D-optimal design was applied to choose the optimized formulations. The maximum desirability values were 0.754 and 0.478 for the optimized formulations containing 0.05 g CA, 0.18 g T80, and 0.5 g mannitol (OFM) or Aerosil (OFA), respectively. In vitro drug release from the optimized formulations showed a significantly faster dissolution rate when compared to the market product. In vivo performance of the optimized formulations in rabbits was investigated after filling them into enteric-coated capsules. Ultimately, OFA formulation achieved a 3 times increase in RC oral bioavailability in comparison with the market product, supporting the hypothesis of considering IFNs as promising nanocarriers able to boost the bioavailability of BCS class II drugs.

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