不同处方盐酸氨溴索吸入溶液雾化特性比较

Comparison of nebulization characteristics of different formulations for ambroxol hydrochloride inhalation solution

目的:对相同规格不同处方的3种盐酸氨溴索吸入溶液的雾化特性进行研究,并考察处方对吸入溶液理化性质及雾化特性的影响。方法:测定不同处方的3种盐酸氨溴索吸入溶液的黏度、表面张力、pH值及渗透压等理化性质,使用新一代撞击器(NGI)及呼吸模拟装置对不同处方的盐酸氨溴索吸入溶液的空气动力学粒径分布(aerodynamic particle size distribution,APSD)、递送速率和递送总量进行测定。结果:处方2与处方3溶液的pH值、渗透压有显著差异,表面张力无显著差异,未见处方的pH值和渗透压对雾化特性有显著影响。处方1与处方2、处方3溶液的pH值、渗透压、表面张力均存在显著差异,处方1溶液的微细粒子剂量(fine particle dose,FPD)为0.42 mg大于处方2、处方3溶液的0.38,0.39 mg,具有显著性差异。处方1溶液递送速率与递送总量均明显大于处方2、处方3溶液。结论:盐酸氨溴索吸入溶液剂处方的表面张力对其雾化特性影响较大。盐酸氨溴索吸入溶液处方1中加入防腐剂,导致溶液表面张力减小,FPD值增大,递送速率和递送总量增大,递送效率增加,但处方设计时应考虑防腐剂的安全性。

Objective: To compare the nebulization characteristics of three different formulations for ambroxolhydrochloride inhalation solution with the same strength by using NGI and breathe simulator and to investigate theinfluence of formulation composition onin vitroperformance.Methods: The physical properties(viscosity, surfacetension, the pH and osmotic pressure) of the three formulations of ambroxol hydrochloride inhalation solution wereinvestigated. The nebulization characteristics( aerodynamic particle size distribution, delivery rate and the totaldelivery) by NGI and breath simulator with different formulations of ambroxol hydrochloride inhalation solution wereinvestigated as well.Results: The pH value and the osmotic pressure between formulations 2 and 3 were significantlydifferent;the surface tension between formulations 2 and 3 did not show significant difference;the same nebulizationcharacteristics were obtained for formulations 2 and 3. pH value,the osmotic pressure and the surface tension offormulation 1 were significantly different compared with that of formulation 2 and 3. The fine particle dose(FPD)of formulation 1 was 0. 42 mg, significantly higher than that of formulations 2 and 3(0. 38 mg and 0. 39 mg,respectively). The delivery rate and total delivery amount of formulation 1 were significantly higher than that offormulations 2 and 3.Conclusion: The formulation compositions of ambroxol hydrochloride inhalation solution havesignificant influence on its nebulization characteristics. When the surface tension of the formulation decreased, theFPD, the delivery rate and the total amount increased, as well as delivery efficiency. However, the safety ofbenzalamine or equivalent preservatives should be well considered during the formulation development.