Investigation of Rheological Characteristics of Thermosensitive Nasal In Situ Gels Based on P407 and Their Effect on Spray Pattern

基于P407的热敏性鼻腔原位凝胶流变特性及其对喷雾模式的影响研究

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Abstract

This article presents the results of a study on the rheological characteristics of in situ thermosensitive nasal gels based on poloxamer 407 (P407) and their effect on spray angle. The development of new drug delivery systems based on in situ thermosensitive gels can overcome several shortcomings of traditional nasal sprays associated with mucociliary clearance and low mucoadhesion. Using the cold method, samples based on P407 were prepared in pure form, in combination with poloxamer 188 (P188), and with the addition of several mucoadhesive polymers: chitosan, sodium alginate, and hydroxypropyl methylcellulose (HPMC). Analytical studies were carried out for all obtained samples, which showed that the gelling temperature (T(sol-gel)) of compositions with P407 was inversely dependent on its concentration, decreasing from 32.71 °C to 24.63 °C. The addition of hydrophilic P188 increased T(sol-gel). The addition of mucoadhesive polymers had varying effects on T(sol-gel): chitosan and HPMC increased the temperature, while sodium alginate decreased it. The addition of mucoadhesive polymers significantly affected the viscosity of the formulations; for example, the addition of sodium alginate resulted in a fivefold increase, making the formulations unsuitable for spraying. A study of the spray angles of T(sol-gel) samples in the range of 27-31 °C using the SprayVIEW measuring system revealed an inverse relationship between the viscosity of the formulations and the spray angle. A mathematical model of the solution droplet trajectory was presented, enabling the spray angle to be predicted depending on the formulation composition. The relative error of the computational experiments did not exceed 10%. This approach has the potential to reduce the number of full-scale experiments, and consequently their cost.

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