Scalable flibanserin nanocrystal-based novel sublingual platform for female hypoactive sexual desire disorder: engineering, optimization adopting the desirability function approach and in vivo pharmacokinetic study

Abstract

Flibanserin (FLB) was approved by FDA for the treatment of pre-menopausal female hypoactive sexual desire disorder (HSDD). FLB suffers from low oral bioavailability (33%) which might be due to hepatic first-pass metabolism in addition to its poor aqueous solubility. The sublingual route could be a promising alternative for FLB due to the avoidance of enterohepatic circulation. However, the drug needs to dissolve in the small volume of saliva in order to be absorbed through the sublingual mucosa. Therefore, FLB nanocrystals were prepared by sono-precipitation technique according to 2 3 full factorial design. FLB-nanocrystals were formulated using two surfactants (PVP K30 and PL F127) in two different amounts (200 and 400 mg) and the volume of ethanol was either 3 or 5 mL. Nanocrystal formulation was optimized according to the desirability function to have a minimum particle size, zeta potential, polydispersity index, and maximum saturated solubility. The optimized formula had a particle size of 443.12 ± 14.91 nm and a saturated solubility of 23.27 ± 4.62 mg/L which is five times the saturated solubility of FLB. Nanocrystal dispersion of the optimized formula was solidified by freeze-drying and used to prepare rapidly disintegrating sublingual tablets containing Pharmaburst ® as superdisintegrant. Sublingual tablet formulation with the shortest disintegration time (36 s) was selected for the in vivo study. FLB nanocrystal-based sublingual tablets exhibited a two-fold increase in bioavailability with a faster onset of action compared to the commercially available oral formulation. These findings prove the potential application of FLB nanocrystal-based sublingual tablets in the treatment of HSDD.

Compritol-Based Nanostrucutured Lipid Carriers (NLCs) for Augmentation of Zolmitriptan Bioavailability via the Transdermal Route: In Vitro Optimization, Ex Vivo Permeation, In Vivo Pharmacokinetic Study

“…The integrity of the particles was not compromised by the sonication stage, since no structural abnormalities were identified ( Figure 6 B). Similar results were declared by Marianne and Amal [ 83 ], who prepared flibanserin nanoparticles utilizing probe sonication for 10 min; however, the prepared formulae maintained its structure without disruptions.…”

Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro , in silico , and in-vivo study

“…Then, 20 min were spent applying 100 W of ultrasonication (VCX600, Sonics and Materials, Newtown, CT, USA), and then 20 min were spent being homogenized at a speed of 7000 rpm. CFZ-NCs were lyophilized to solidify (Naguib & Makhlouf, 2021 ). An expert can freeze a nanocrystal at 20 °C for the night and then freeze-dry it at 45 °C for 24 h by using Novalyphe-NL500 lyophilize.…”

“…Both lyophilized and purified CFZ-NCs were tested for methanol solubility (Fuguet et al., 2021 ; Naguib & Makhlouf, 2021 ). Further samples were added to methanol in 5 mL screw-capped glass vials before being put in a shaking, thermostatically controlled water bath created by (GFL, Gesellschaft Laboratories, Berlin, Germany).…”

“…The necessary viscosity of the liquid dosage form can be obtained with medium and high molecular weight PVP (serving as a thickening agent), which aids in a steady drip rate, better appearance, dispersion, and physical stability (Józó et al., 2021 ). Sublingual tablet delivery systems and nanocrystals offer various benefits, such as improving solubility and permeability, preventing enzymatic drug-food and drug-food interactions that affect drug gastrointestinal absorption and pass the first-pass effect, and providing continuous-release delivery for many days (Naguib & Makhlouf, 2021 ).…”

Formulation and Evaluation of Baclofen-Meloxicam Orally Disintegrating Tablets (ODTs) Using Co-Processed Excipients and Improvement of ODTs Performance Using Six Sigma Method

“…This could be explained by the higher capacity of crospovidone as a super disintegrant, as it had rapid capillary activity and pronounced hydration with a slight tendency to gel formation. 47 Although F-melt contains crospovidone besides insoluble inorganic salt (dibasic calcium phosphate anhydrous), water-insoluble inorganic excipients enhance the disintegration time than most commonly used water-soluble sugars or salts. In general, tablets composed mainly of water-soluble components tend to dissolve rather than disintegrate, resulting in a much longer disintegration time.…”