Garmise Robert J, Mar Kevin, Crowder Timothy M, Hwang C Robin, Ferriter Matthew, Huang Juan, Mikszta John A, Sullivan Vincent J, Hickey Anthony J
School of Pharmacy, University of North Carolina at Chapel Hill, CB# 7360 Kerr Hall Room 1310, 27599, Chapel Hill, NC.
Becton Dickinson Technologies, 27709, Research Triangle Park, NC.
AAPS PharmSciTech. 2006 Mar;7(1):E131-E137. doi: 10.1208/pt070119. Epub 2017 Mar 8.
The purpose of this research was to prepare a dry powder vaccine formulation containing whole inactivated influenza virus (VIIV) and a mucoadhesive compound suitable for nasal delivery. Powders containing WIIV and either lactose or trehalose were produced by lyophilization. A micro-ball mill was used to reduce the lyophilized cake to sizes suitable for nasal delivery. Chitosan flakes were reduced in size using a cryo-milling technique. Milled powders were sieved between 45 and 125 μm aggregate sizes and characterized for particle size and distribution, morphology, and flow properties. Powders were blended in the micro-ball mill without the ball. Lyophilization followed by milling produced irregularly shaped, polydisperse particles with a median primary particle diameter of ≈21 μm and a yield of ≈37% of particles in the 45 to 125 μm particle size range. Flow properties of lactose and trehalose powders after lyophilization followed by milling and sieving were similar. Cryo-milling produced a small yield of particles in the desired size range (<10%). Lyophilization followed by milling and sieving produced particles suitable for nasal delivery with different physicochemical properties as a function of processing conditions and components of the formulation. Further optimization of particle size and morphology is required for these powders to be suitable for clinical evaluation.
本研究的目的是制备一种含有全灭活流感病毒（VIIV）和适用于鼻腔给药的粘膜粘附化合物的干粉疫苗制剂。通过冻干法制备含有VIIV以及乳糖或海藻糖的粉末。使用微型球磨机将冻干饼研磨至适合鼻腔给药的尺寸。采用低温研磨技术减小壳聚糖薄片的尺寸。将研磨后的粉末筛分为聚集体尺寸在45至125μm之间的粉末，并对其粒度和分布、形态及流动性质进行表征。在无球的微型球磨机中混合粉末。冻干后再进行研磨得到形状不规则、多分散的颗粒，其初级颗粒直径中值约为21μm，在45至125μm粒径范围内颗粒产率约为37%。冻干后再进行研磨和筛分的乳糖和海藻糖粉末的流动性质相似。低温研磨在所需尺寸范围内（<10%）颗粒产率较低。冻干后再进行研磨和筛分得到适合鼻腔给药的颗粒，其物理化学性质因加工条件和制剂成分而异。为使这些粉末适合临床评估，需要进一步优化粒度和形态。
