Intranasal Tadalafil nanoemulsions: formulation, characterization and pharmacodynamic evaluation

Autor:	Nabila Boraie, Sally Galal, Doaa A Abdelmonsif, Bassant Elbardisy
Rok vydání:	2019
Předmět:	Male Vasodilator Agents Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Phase Transition Tadalafil Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Solubility Cyclic GMP Cyclic guanosine monophosphate Administration Intranasal Chromatography Chemistry General Medicine Phosphodiesterase 5 Inhibitors 021001 nanoscience & nanotechnology Rats Bioavailability Pharmacodynamics cGMP-specific phosphodiesterase type 5 Toxicity Emulsions Nasal administration 0210 nano-technology medicine.drug
Zdroj:	Pharmaceutical Development and Technology. 24:1083-1094
ISSN:	1097-9867 1083-7450
DOI:	10.1080/10837450.2019.1631846
Popis:	This study aims at improving the bioavailability of a poorly soluble phosphodiesterase-5 inhibitor; tadalafil (TD) via developing intranasal (IN) nanoemulsions (NEs). Optimum NE ingredients were selected based on solubility studies, emulsification tests, and phase diagram construction. Both o/w and w/o NEs were selected based on their drug loading capacity. Optimum formulations were subjected to physicochemical characterization and were assessed for nasal toxicity through biochemical analysis of tumor necrosis factor-α (TNF-α) and caspase-3 in rat nasal tissues. Pharmacodynamic study was performed via biochemical analysis of cyclic guanosine monophosphate (cGMP) in rat penis 2-h post-treatment and compared with oral suspension of Cialis® tablets. Optimum o/w and w/o NEs were successfully prepared using different ratios of Capmul-MCM-EP, Labrasol:Transcutol-HP (1:1) and water. Optimized formulations exhibited more than 4000-fold increase in TD solubility compared with its aqueous solubility. Both formulations were optically isotropic with the majority of globules in the nanometric-size range. Nasal toxicity study revealed no significant difference in values of TNF-α and caspase-3 between the NE-treated groups and the control group. Both TD-NEs succeeded to achieve a significant enhancement in cGMP levels. Our findings suggested that IN administration of the developed TD-NEs could provide a safe and effective alternative to TD oral delivery.
Databáze:	OpenAIRE
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