Development ofin situgel for nasal delivery: design, optimization,in vitroandin vivoevaluation

Abstract

Context: The mucoadhesive gel formulations are helpful to prolong the residence time at the nasal absorption site and thereby facilitate the uptake of drug. Sumatriptan succinate has oral bioavailability of 15% and undergoes hepatic metabolism, hence it is suitable for nasal administration.Objective: The objective of the investigation was to develop a mucoadhesive in situ gel to improve the bioavailability of the sumatriptan succinate. Materials and methods: Deacetylated gellan gum was used as gelling agent. In situ gel was formulated by ion activation mechanism in simulated nasal fluid. A 3 2 factorial design was found suitable to optimize batch. In vivo study was carried out in Spraugue-Dawley rats, and drug was estimated in plasma by UPLC-MS. Result: The optimized batch showed drug release of 98.57% within 5 h followed by Peppas model of drug release. Ex vivo studies on sheep nasal mucosa showed 93.33% within 5 h. In histopathological study, optimized batch was found to be safe and stable in accelerated stability study for three months. Optimized formulation, F7 has shown absolute bioavailability, which was found to be 164.70%. Drug targeting index for brain tissues was found to be 1.866. Discussion: Concentration of the gelling polymer was compromised for satisfactory gel strength and an acceptable viscosity. The release depended on viscosity of formulation. Drug targeting index indicates sumatriptan can reach to brain via olfactory pathway. Conclusion: In situ gel proved to be suitable for administration of sumatriptan succinate through nasal route. The ease of administration coupled with less frequent administration enhances patient compliance.

Formulation Development and in Vitro Evaluation of in Situ Lisinopril Gel for Nasal Administration

“…At fixed time interval, 20 s, the surface area covered by the formulation was measured. [4] Ex vivo permeation studies …”

“…The refractometer scale was adjusted in such a way that the cross wire of the telescope was exactly on the boundary between the bright and dark regions. The procedure was repeated for all formulations F1 to F4 and the results were compared with refractive index of water (1.33), [4] PH Digital pH meter (Chemline, CL180, India) was calibrated by using pH buffer of 4 and 7.…”

“…[4,8] www.wjpr.net Abbe's refractometer has been used to measure the refractive index of liquids. The clarity of solutions, that is formulations before gelling, was determined in term of refractive index using Abbes refractometer.…”

“…Lipophilic drugs are transported transcellularly by a concentration dependent passive diffusion process, by facilitated diffusion using a receptor or carrier molecule, or by vesicular transport mechanisms. [4] A significant challenge to the formulator is to overcome the protective barriers of the nasal cavity without causing permanent tissue damage. The major problems that persist with nasal solutions are cleared off rapidly from nasal cavity.…”

Design and Evaluation of a Brinzolamide Drug–Resin <i>in Situ</i> Thermosensitive Gelling System for Sustained Ophthalmic Drug Delivery

“…In situ gels can be classified as pH-triggered, temperature-dependent and ion-activated system. 16,17) The oldest and most common system is the temperature sensitive type in situ gel. The aim of this study was to prepare and evaluate a brinzolamide drug-resin ophthalmic thermosensitive in situ gel.…”