Wong Joseph, Papadopoulos Pavlos, Werling Jane, Rebbeck Christine, Doty Mark, Kipp James, Konkel Jamie, Neuberger Damian
Scientific Affairs, BioPharma Solutions, Baxter Healthcare Corporation, Round Lake, IL 60073, USA.
PDA J Pharm Sci Technol. 2006 Sep-Oct;60(5):302-13.
The purpose of this study is to assess the impact of real refractive indices, using different itraconazole suspensions, on the associated particle size distributions. Instrumental particle size measurement remains the practical option for determining the particle size distribution of a suspension. In this study, the suspension particle size distribution was measured by static light scattering, which requires knowledge of both the real and imaginary components of the complete refractive index. The real refractive indices of micronized itraconazole raw material, as well as vacuum-dried itraconazole suspension samples obtained from different formulations, polymorphs, manufacturing methods and particle size distributions, were determined using the Becke line method. Identical samples were analyzed by two contract laboratories in order to assess consistency. For the static light scattering equipment used in this study, the complete relative refractive index (RRI = n(particte) / n(dispersant) - ik) input required for software calculation is denoted by a refractive index kernel (RRI input) comprising a relative real component and an imaginary component. The reported real refractive indices for the itraconazole raw material as well as vacuum dried itraconazole suspension samples were different, ranging from 1.608 to 1.65 (selected kernel range of 120A010I to 124A010I). The imaginary component of itraconazole suspension was determined in a previous study to be 010I. The average real refractive index was calculated to be 1.62 (122A010I). The particle size distributions obtained using 120A010I and 124A010I were in good agreement with one generated using 122A010I. Therefore, itraconazole suspensions that were produced using different manufacturing methods/formulations or exhibited different particle size distributions/polymorphic forms may use 122A010I in determining particle size distribution. The particle size distributions determined using RRI input outside the range of 120A010I to 124A010I may not be reliable. However, it is recommended that similar investigations be conducted for other drug suspensions on a case-by-case basis.
本研究的目的是评估使用不同伊曲康唑悬浮液时，实际折射率对相关粒径分布的影响。仪器粒度测量仍然是确定悬浮液粒径分布的实用方法。在本研究中，通过静态光散射测量悬浮液的粒径分布，这需要完整折射率的实部和虚部的知识。使用贝克线法测定了微粉化伊曲康唑原料以及从不同配方、多晶型、制造方法和粒径分布获得的真空干燥伊曲康唑悬浮液样品的实际折射率。两个合同实验室对相同样品进行了分析，以评估一致性。对于本研究中使用的静态光散射设备，软件计算所需的完整相对折射率（RRI = n(颗粒)/n(分散剂) - ik）输入由包含相对实部和虚部的折射率内核（RRI输入）表示。报道的伊曲康唑原料以及真空干燥伊曲康唑悬浮液样品的实际折射率不同，范围为1.608至1.65（选定内核范围为120A010I至124A010I）。在先前的一项研究中确定伊曲康唑悬浮液的虚部为010I。计算得出平均实际折射率为1.62（122A010I）。使用120A010I和124A010I获得的粒径分布与使用122A010I生成的粒径分布高度一致。因此，使用不同制造方法/配方生产的或表现出不同粒径分布/多晶型形式的伊曲康唑悬浮液在确定粒径分布时可使用122A010I。使用120A010I至124A010I范围之外的RRI输入确定的粒径分布可能不可靠。然而，建议针对其他药物悬浮液逐案进行类似研究。
