Zolmitriptan is the drug of choice for migraine, but low oral bioavailability (<50%) and recurrence of migraine lead to frequent dosing and increase in associated side effects. Increase in the residence time of drug at the site of drug absorption along with direct nose to brain targeting of zolmitriptan can be a solution to the existing problems. Hence, in the present investigation, thermoreversible intranasal gel of zolmitriptan-loaded nanoethosomes was formulated by using mucoadhesive polymers to increase the residence of the drug into the nasal cavity. The preparation of ethosomes was optimized by using 3(2) factorial design for percent drug entrapment efficiency, vesicle size, zeta potential, and polydispersity index. Optimized formulation E6 showed the vesicle size (171.67 nm) and entrapment efficiency (66%) when compared with the other formulations. Thermoreversible gels prepared by using poloxamer 407 showed the phase transition temperature at 32-33 °C which was in line with the nasal physiological temperature. The optimized ethosomes were loaded into the thermoreversible mucoadhesive gel optimized by varying concentrations of poloxamer 407, carbopol 934, HPMC K100, and evaluated for gel strength, gelation temperature, mucoadhesive strength, in vitro drug release, and ex vivo drug permeation, where G3 and G6 were found to be optimized formulations. In vitro drug release was studied by different kinetic models suggested that G3 (n = 0.582) and G6 (n = 0.648) showed Korsemeyer-Peppas (KKP) model indicating non-Fickian release profiles. A permeation coefficient of 5.92 and 5.9 µg/cm(2) for G3 and G6, respectively, revealed very little difference in release rate after 24 h between both the formulations. Non-toxic nature of the gels on columnar epithelial cells was confirmed by histopathological evaluation.

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The objective of the present investigation was to formulate and characterize the human insulin entrapped Eudragit S100 microspheres containing protease inhibitors and to develop an optimized formulation with desirable features. A w/o/w multiple emulsion solvent evaporation technique was employed to produce microspheres of human insulin using Eudragit S-100 as coating material and polyvinyl alcohol as a stabilizer. The resultant microspheres were evaluated for drug-excipient compatibility, encapsulation efficiency, particle size, surface morphology, micromeritic properties, enteric nature, and in vitro drug release studies. Micromeritic properties indicated good flow properties and compressibility. In present investigation formulation F6 with drug/polymer ratio (1:100) was found to be optimal in terms of evaluated parameters where it showed a significantly higher percentage of encapsulation efficiency (76.84%) with minimal drug release (3.25%) in an acidic environment. The optimized formulation (F6) also possessed good spherical shape and particle size (57.42 µm) required to achieve the desired in vitro drug release profile at pH 7.4. The results confirmed that human insulin-loaded Eudragit S-100 microspheres containing protease inhibitor possessed good encapsulation efficiency, pH dependant controlled release carrying encapsulated insulin to its optimum site of absorption. This ultimately resulted in enhanced insulin absorption and biological response.Graphical Abstract