Abstract
Flibanserin (FLB) is a nonhormonal medicine approved by the Food and Drug Administration (FDA) to treat the hypoactive sexual appetite disorder in females. However, the peroral administration of the medicine is greatly affected by its poor bioavailability as a result of its extensive first-pass effect and poor solubility. Aiming at circumventing these drawbacks, this work involves the formulation of optimized FLB transfersome (TRF) loaded intranasal hydrogel. Box–Behnken design was utilized for the improvement of FLB TRFs with decreased size. The FLB-to-phospholipid molar ratio, the edge activator hydrophilic lipophilic balance, and the pH of the hydration medium all exhibited significant effects on the TRF size. The optimized/developed TRFs were unilamellar in shape. Hydroxypropyl methyl cellulose based hydrogel filled with the optimized FLB TRFs exhibited an improved ex vivo permeation when compared with the control FLB-loaded hydrogel. In addition, the optimized TRF-loaded hydrogel exhibited higher bioavailability and enhanced brain delivery relative to the control hydrogel following intranasal administration in Wistar rats. The results foreshadow the possible potential application of the proposed intranasal optimized FLB-TRF-loaded hydrogel to increase the bioavailability and nose-to-brain delivery of the drug.
Highlights
Flibanserin (FLB) is a recently Food and Drug Administration (FDA)-approved nonhormonal drug for the treatment of women with hypoactive sexual appetite disorder
The nanoscale size observed could contribute to enhancing the drug permeation via the nasal mucosa and facilitating passing through the blood–brain barrier
The positive sign of the coefficients of the linear terms X1 and X2 indicates that the vesicle size increases significantly with increasing drug:PL molar ratio and/or surfactant hydrophilic lipophilic balance (HLB)
Summary
Flibanserin (FLB) is a recently FDA-approved nonhormonal drug for the treatment of women with hypoactive sexual appetite disorder. FLB-treated women have demonstrated significant improvements in both the number of satisfying sexual events and the female sexual function index desire domain score compared placebo-treated ones. These findings proved the ability of the drug to enhance the women’s sexual desire. Administration of FLB was linked with a significant reduction in the distress related with either sexual dysfunction or low sexual desire [2,3,4,5]. The major challenge for oral administration of FLB is the reduced bioavailability (~33%) that might be caused by the drug’s low solubility and its exposure to hepatic first-pass metabolism [6,7]
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