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The use of hydrophobic amino acids in protecting spray dried trehalose formulations against moisture-induced changes.
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.4 ) Pub Date : 2019-09-16 , DOI: 10.1016/j.ejpb.2019.09.014 Pei T Mah 1 , Peter O'Connell 1 , Stefano Focaroli 1 , Ross Lundy 2 , Tom F O'Mahony 2 , Jayne E Hastedt 3 , Irina Gitlin 4 , Stefan Oscarson 5 , John V Fahy 4 , Anne Marie Healy 6
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.4 ) Pub Date : 2019-09-16 , DOI: 10.1016/j.ejpb.2019.09.014 Pei T Mah 1 , Peter O'Connell 1 , Stefano Focaroli 1 , Ross Lundy 2 , Tom F O'Mahony 2 , Jayne E Hastedt 3 , Irina Gitlin 4 , Stefan Oscarson 5 , John V Fahy 4 , Anne Marie Healy 6
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Trehalose is commonly used as a protein stabilizer in spray dried protein formulations delivered via the pulmonary route. Spray dried trehalose formulations are highly hygroscopic, which makes them prone to deliquescence and recrystallization when exposed to moisture, leading to impairment in aerosolization performance. The main aim of this study was to investigate and compare the effect of hydrophobic amino acids (i.e. L-leucine and L-isoleucine) in enhancing aerosolization performance and in mitigating moisture-induced changes in spray dried trehalose formulations. Trehalose was spray dried with 20-60% w/w of amino acid (i.e. L-leucine or L-isoleucine). The spray dried formulations were stored at 25 °C/50% RH for 28 days. Solid state characterization and in vitro aerosolization performance studies were performed on the spray dried formulations before and after storage. The addition of 20-60% w/w of amino acid (i.e. L-leucine or L-isoleucine) improved the emitted fractions of spray dried trehalose formulations from a dry powder inhaler. However, ≥ 40% w/w of L-leucine/L-isoleucine was needed to prevent recrystallization of trehalose in the formulations when exposed to 25 °C/50% RH for 28 days. X-ray photoelectron spectroscopy (XPS) demonstrated that samples with 40-60% w/w L-isoleucine had more amino acid on the surfaces of the particles compared to their L-leucine counterparts. This may explain the greater ability of the L-isoleucine (40-60% w/w) samples to cope with elevated humidity compared to L-leucine samples of the same concentrations, as observed in the dynamic vapour sorption (DVS) studies. In conclusion, this study demonstrated that both L-leucine and L-isoleucine were effective in enhancing aerosolization performance and mitigating moisture-induced reduction in aerosolization performance in spray dried trehalose formulations. L-isoleucine proved to be superior to L-leucine in terms of its moisture protectant effect when incorporated at the same concentration in the formulations.
中文翻译：
疏水氨基酸在保护喷雾干燥海藻糖制剂中防止水分引起的变化中的用途。
在通过肺途径递送的喷雾干燥的蛋白质制剂中，海藻糖通常用作蛋白质稳定剂。喷雾干燥的海藻糖制剂具有高度吸湿性，这使它们在暴露于湿气时易于潮解和重结晶，从而导致雾化性能受损。这项研究的主要目的是研究和比较疏水性氨基酸（即L-亮氨酸和L-异亮氨酸）在提高喷雾干燥海藻糖配方的雾化性能和减轻水分引起的变化方面的作用。将海藻糖用20-60％w / w的氨基酸（即L-亮氨酸或L-异亮氨酸）喷雾干燥。将喷雾干燥的制剂在25℃/ 50％RH下储存28天。在储存之前和之后，对喷雾干燥的制剂进行了固态表征和体外雾化性能研究。添加20-60％w / w的氨基酸（即L-亮氨酸或L-异亮氨酸）可改善干粉吸入器中喷雾干燥海藻糖制剂的排放分数。然而，当暴露于25°C / 50％RH 28天时，需要≥40％w / w的L-亮氨酸/ L-异亮氨酸来防止制剂中的海藻糖重结晶。X射线光电子能谱（XPS）表明，与L-亮氨酸对应物相比，具有40-60％w / w L-异亮氨酸的样品在颗粒表面具有更多的氨基酸。这可能解释了与相同浓度的L-亮氨酸样品相比，L-异亮氨酸样品（40-60％w / w）具有更高的应付湿度的能力，如在动态蒸气吸附（DVS）研究中所观察到的。总之，这项研究表明，L-亮氨酸和L-异亮氨酸均能有效提高喷雾干燥海藻糖制剂的雾化性能并减轻湿气导致的雾化性能下降。当以相同的浓度掺入制剂中时，L-异亮氨酸被证明在L-亮氨酸方面具有优异的水分保护作用。
更新日期：2019-09-16
中文翻译：
疏水氨基酸在保护喷雾干燥海藻糖制剂中防止水分引起的变化中的用途。
在通过肺途径递送的喷雾干燥的蛋白质制剂中，海藻糖通常用作蛋白质稳定剂。喷雾干燥的海藻糖制剂具有高度吸湿性，这使它们在暴露于湿气时易于潮解和重结晶，从而导致雾化性能受损。这项研究的主要目的是研究和比较疏水性氨基酸（即L-亮氨酸和L-异亮氨酸）在提高喷雾干燥海藻糖配方的雾化性能和减轻水分引起的变化方面的作用。将海藻糖用20-60％w / w的氨基酸（即L-亮氨酸或L-异亮氨酸）喷雾干燥。将喷雾干燥的制剂在25℃/ 50％RH下储存28天。在储存之前和之后，对喷雾干燥的制剂进行了固态表征和体外雾化性能研究。添加20-60％w / w的氨基酸（即L-亮氨酸或L-异亮氨酸）可改善干粉吸入器中喷雾干燥海藻糖制剂的排放分数。然而，当暴露于25°C / 50％RH 28天时，需要≥40％w / w的L-亮氨酸/ L-异亮氨酸来防止制剂中的海藻糖重结晶。X射线光电子能谱（XPS）表明，与L-亮氨酸对应物相比，具有40-60％w / w L-异亮氨酸的样品在颗粒表面具有更多的氨基酸。这可能解释了与相同浓度的L-亮氨酸样品相比，L-异亮氨酸样品（40-60％w / w）具有更高的应付湿度的能力，如在动态蒸气吸附（DVS）研究中所观察到的。总之，这项研究表明，L-亮氨酸和L-异亮氨酸均能有效提高喷雾干燥海藻糖制剂的雾化性能并减轻湿气导致的雾化性能下降。当以相同的浓度掺入制剂中时，L-异亮氨酸被证明在L-亮氨酸方面具有优异的水分保护作用。
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