Abstract

 Sumatriptan(ST) is a selective agonist at serotonin 5-HTI receptors, as well as 5-HT1B/1D subtypes. It is effective for acute migraine attacks, but has a short half life (about 2 hours) and low oral bioavailability (15%). The purpose of this study was to develop and optimize nasal mucoadhesive in-situ gel(IG) of ST to enhance nasal residence time for migraine management. Cold method was used to prepare different formulas of ST nasal IG, using thermosensitive polymers (poloxamer 407 alone or with poloxamer 188) with a mucoadhesive polymer hyaluronic acid (HA) which were examined for gelation temperature and gelation time, pH, drug content, gel strength, spreadability, mucoadhesive force determination, viscosity, in-vitro drug release, and the selected formula was subjected to fourier transform infrared (FTIR) compatibility studies, and to ex-vivo permeation study, histological evaluation of the sheep mucosal tissue after ST nasal gel application for 6 hours.The results showed that the formula IG7 prepared from poloxamer 407(19%), poloxamer188 (4%) and HA (0.5%) had an optimum gelation temperature (32.66±1.52°C), gel strength (43.66± 1.52 sec), mucoadhesive force (8067.93± 746.45dyne\cm2), in-vitro drug release (95.98%) over 6h, ex-vivo permeation study (89.6%) during the 6 h. study with no histological or pathological change in the nasal sheep tissue and no interaction between drug and other additives in IG7. Formulation of ST as a nasal insitu gel to avoid first pass metabolism and ease of administration coupled with less frequent and sustained drug release, will enhance patient compliance.
Highlights
Drug delivery by nasal route is one of the challenging endeavors facing the pharmaceutical technologist today
The addition of poloxamer188 increases the ratio of polyethylene oxide (PEO) leading the micelles to become less entangled there by raising the critical micelle temperature (CMT)(22)
In cases of mixtures of poloxamer407 and poloxamer188, several formulations gelled at the body temperature
Summary
Drug delivery by nasal route is one of the challenging endeavors facing the pharmaceutical technologist today. Approaches enhancing the nasal bioavailability is either by prolonging the contact time with the nasal surface via a viscosity-enhancing agent or in-situ gelling polymers or both approaches. An in-situ gel is a drug delivery system that exhibits sol-to-gel phase transition due to a change in specific physicochemical parameters such as ionic, temperature or pH[2]. Thermoreversible polymers are substances having both solid and liquid-like properties which can be transported as a fluid and solidifies within the body temperature. The formulation has the advantage to stop the anterior leakage of the dosage form, reduce the taste impact and enhance the nasal bioavailability[2]
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