Department of Pharmaceutical Technology, School of Pharmacy, Istanbul Medipol University, 34815, Istanbul, Turkey.
Department of Microbiology, School of Pharmacy, Istanbul Medipol University, 34815, Istanbul, Turkey.
AAPS PharmSciTech. 2023 Oct 17;24(8):214. doi: 10.1208/s12249-023-02674-w.
Benzydamine hydrochloride (BZD) having analgesic, anesthetic, and anti-inflammatory effects is used orally or topically in the treatment of disorders such as joint inflammation and muscle pain. Within the scope of this study, sprayable thermosensitive BZD hydrogels were developed using thermoresponsive poloxamers to avoid systemic side effects and to provide better compliance for topical administration. Also, hydroxypropyl methyl cellulose (HPMC) was employed to improve the mechanical strength and bioadhesive properties of the hydrogel. The addition of BZD generally decreased the viscosity of the formulations (p < 0.05), while increasing the gelation temperature (p < 0.05). The formulations that did not have any clogs or leaks in the nozzle of the bottle during the spraying process were considered lead formulations. To spray the formulations easily, it was found that the viscosity at RT should be less than 200 mPa·s, and their gelation temperature should be between 26 and 34°C. Increasing HPMC and poloxamer improved bioadhesion. The amount of HPMC and poloxamers did not cause a significant change in the release characteristics of the formulations (p > 0.05); the release profiles of BZD from the formulations were similar according to model-independent kinetic (f2 > 50). HPMC and poloxamers had important roles in the accumulation of BZD in the skin. In vitro biological activity studies demonstrated that the formulations presented their anti-inflammatory activity with TNF-α inhibition but did not have any effect on the inhibition of COX enzymes as expected. As a result, thermosensitive hydrogels containing BZD might be an appropriate alternative, providing an advantage in terms of easier application compared to conventional gels.
盐酸苯佐卡因（BZD）具有镇痛、麻醉和抗炎作用，可口服或局部用于治疗关节炎和肌肉疼痛等疾病。在本研究范围内，使用温敏性泊洛沙姆开发了可喷涂的温敏 BZD 水凝胶，以避免全身副作用，并为局部给药提供更好的顺应性。此外，还使用羟丙基甲基纤维素（HPMC）来提高水凝胶的机械强度和生物粘附性能。BZD 的添加通常会降低制剂的粘度（p<0.05），同时会升高凝胶化温度（p<0.05）。在喷涂过程中，制剂在瓶盖上的喷嘴处没有任何堵塞或泄漏的被认为是先导制剂。为了方便喷涂制剂，发现 RT 时的粘度应小于 200 mPa·s，其凝胶化温度应在 26 至 34°C 之间。增加 HPMC 和泊洛沙姆可提高生物粘附性。HPMC 和泊洛沙姆的用量不会导致制剂释放特性发生显著变化（p>0.05）；根据无模型动力学（f2>50），BZD 从制剂中的释放曲线相似。HPMC 和泊洛沙姆在 BZD 在皮肤中的积累中起重要作用。体外生物活性研究表明，这些制剂表现出抗炎活性，抑制 TNF-α，但如预期的那样，对 COX 酶的抑制没有任何作用。因此，含有 BZD 的温敏水凝胶可能是一种合适的替代物，与传统凝胶相比，具有更易于应用的优势。
