Formulation of Convenient, Easily Scalable, and Efficient Granisetron HCl Intranasal Droppable Gels

• Published in: Molecular pharmaceutics 2015-06, Vol.12 (6), p.2019-2025
• Main Authors: Ibrahim, Howida K, Abdel Malak, Nevine S, Abdel Halim, Sally A
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Animals; Drug Stability; Gels - chemistry; Granisetron - pharmacokinetics; Models, Theoretical; Nasal Mucosa - metabolism; Sheep
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/mp500825n

Deacetylated gellan gum and two sodium alginate polymer types were used each at three concentrations in the suitable range for their sol-gel transition. The prepared nine droppable gels were evaluated in vitro, ex vivo through sheep nasal mucosa, as well as in vivo in comparison to drug solution given intravenously and orally at the same dose. The prepared formulas gelled instantaneously in simulated nasal fluid and the obtained gels sustained their shear thinning and thixotropic behavior up to 48 h. Polymer type and concentration had significant effects on the apparent viscosities and the in vitro release profile of granisetron from the prepared gels. The drug release data best fitted a modified Higuchi equation with initial burst and followed Fickian diffusion mechanism. A 0.5% gellan-gum-based formula sustained the in vitro drug release up to 3 h and enhanced the drug permeation without need for an enhancer. The histopatholgical study revealed the safety of the tested formula. Intranasal delivery recorded double the drug bioavailabilty in comparison to the oral route. It had an absolute bioavailability of 0.6539 and the maximum plasma drug concentration reached after 1.5 h. The developed formula could be promising for the management of chemotherapy-induced nausea and vomiting regarding its improved bioavailability, patient acceptability, and ease of production.