Self-Nanoemulsifying/ Self-Assembled Cubic Nanoparticles Lyophilized Tablet: A Novel Biphasic Release Approach to Enhance the Bioavailability of a Lipophilic Drug

• Published in: AAPS PharmSciTech Vol. 25; no. 8; p. 250
• Main Authors: Farag, Michael M., El-Sebaie, Wessam, Basalious, Emad B., El-Gazayerly, Omaima N.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 21.10.2024
• Subjects: Animals; Biochemistry; Biological Availability; Biomedical and Life Sciences; Biomedicine; Biotechnology; Chemistry, Pharmaceutical - methods; Cross-Over Studies; Delayed-Action Preparations - pharmacokinetics; Drug Liberation; Emulsions; Freeze Drying - methods; Male; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - chemistry; Muscarinic Antagonists - pharmacokinetics; Nanoparticles - chemistry; Pharmacology/Toxicology; Pharmacy; Rabbits; Research Article; Solubility; Tablets; bi-phasic release; nocturia; darifenacin; LC–MS/MS; lyophilisation; overactive bladder
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-024-02952-1

This study aimed to prepare a combined self-nanoemulsifying and self-assembled cubic nanoparticles (SNE/SAC) lyophilized tablet eliciting biphasic release pattern escorted with enhanced bioavailability for drugs hampered with slow dissolution and poor absorption. The antimuscarinic Darifenacin hydrobromide (DRF) was selected as a model drug used to treat overactive bladder-associated nocturia. The DRF-SNE/SAC lyophilized tablet was prepared so that upon reconstitution a mixture of DRF-loaded cubic nanoparticles and nanoemulsion dispersion is obtained. The nanoemulsion portion is responsible for the fast release followed by controlled release of the remaining dose loaded in cubic nanoparticles. A comparative pharmacokinetic study adopting randomized crossover design in male albino rabbits versus marketed product Frequefenacine® tablet was performed. Half of the dose (52.05% ± 4.21%) was rapidly released in the first 4 h followed by sustained release of the remaining drug where (90.16% ± 8.85%) was released in 24 h. The tested system showed 2.45 folds higher % relative bioavailability and 1.57 folds higher C max with 1.62 longer residence time relative to reference product. The results endow the ability of the developed DRF-SNE/SAC lyophilized tablet to be considered as a propitious approach for the treatment of overactive bladder-associated nocturia without midnight dose administration. Graphical Abstract