Investigation Of Influence Factors On Particle Size Measurement With PMDI

There are many factors that influence the pMDI therapy performance,such as particle size.LD and NGI were recommended for measurement of particle size for pMDI in Pharmacopoeia.Existing literature had shown that some influence factors affect in vitro aerosol drug delivery of pMDI.This study investigated the effect of temperature on the MMAD and FPF of the pMDI by NGI.And also studied the effect of environmental condition(temperature and humidity),flow rate and device temperature on the Dv(50)of two commercial pMDI by LD.The results were analyzed by t-test: p<0.05 is significant difference,p<0.01 is highly dominant difference.Following are the main work and conclusions of this study:⑴Effects of the system temperature(NGI).FPF and MMAD tested between 5℃ and25 ℃ have a highly dominant difference.MMAD tested at 5 ℃ increased by38.14%(Ventolin),73.75%(Atrovent),respectively,compared with at 25℃;FPF reduced56.57%(Ventolin),56.79%(Atrovent).⑵Effects of the system temperature(LD).Ventolin: Dv(50)tested at 40 ℃ increased by37.57% and 33.47%,respectively,compared with at 25℃ and 5℃.It was a highly dominant difference,but no significant difference between at 25℃ and 5℃.Atrovent: Dv(50)tested at40℃ and 25℃ increased by 48.00% and 47.59%,respectively,compared with at 5℃.It was a highly dominant difference,but no significant difference between at 25℃ and 40℃.⑶ Effects of the system humidity(LD).Dv(50)tested at RH25±1.3% increased by23.29%(Ventolin)and 34.58%(Atrovent),respectively,compared with RH>90%.Both were a highly dominant difference.⑷ Effects of the flow rate(LD).Ventolin: Dv(50)tested at 0L/min increased by47.51%,38.25% and 41.48%,respectively,compared with at 40L/min,30L/min and 15L/min.It was a highly dominant difference,but no significant difference between at40L/min,30L/min and 15L/min.Atrovent: Dv(50)tested at 40L/min decreased by 16.84% and13.80%,respectively,compared with at 15L/min and 30L/min.It was a highly dominant difference.Dv(50)tested at 50L/min decreased 11.56%,compared with at 40L/min(highly dominant difference),no significant difference between at 30L/min and 15L/min.0L/mincannot trigger the measurement.⑸Effects of the pMDI temperature(LD).Ventolin: Dv(50)tested at 40 ℃ increased by63.10% and 62.25%,respectively,compared with at 25℃ and 60℃.It was a highly dominant difference,but no significant difference between at 25℃ and 60℃.Atrovent: Dv(50)tested at25 ℃ increased by 29.76% and 27.62%,respectively,compared with at 40 ℃ and 60 ℃(highly dominant difference).Dv(50)tested at 60℃ increased 2.96%,compared with at 40℃.Conclusion: Those factors above had significant influence on the performance of LD or NGI,and should be controlled in the particle size measurement of pMDI Development.Until now,there is no uniform definition of the influencing factors in particle size tests in pharmacopoeia of each country.So,the result of this study has reference value and guidance significance to pharmacopoeia.