A method to reproducibly mill abuse deterrent oxycodone hydrochloride (HCl) extended release (ER) tablets was developed for a nasal insufflation pharmacokinetic (PK) study. Several comminution methods were explored before determining that a conical mill resulted in controlled milling of tablets to a size range equal to or below 1000 μm. However, milling resulted in significant loss of oxycodone from abuse deterrent oxycodone HCl ER tablets compared to minimal oxycodone loss from oxycodone HCl immediate release (IR) tablets. Characterization of milled tablet powder showed that loss of oxycodone was not attributed to analytical procedures or oxycodone phase change during high intensity milling processes. The content uniformity of oxycodone in the milled tablet powder varied when ER and IR tablets were milled to a particle size distribution equal to or below 500 μm but did not vary when particles were sized above 500 µm to equal to or below 1000 μm. In addition, the initial excipient weight to drug substance weight ratio impacted the amount of oxycodone lost from the respective formulation. However, dissolution demonstrated that when oxycodone HCl ER tablets are milled, differences in excipient weight to drug substance weight ratio and particle size distribution of milled tablets did not result in significantly different release of oxycodone.

开发了一种可重复研磨抑制滥用盐酸羟考酮 (HCl) 缓释 (ER) 片剂的方法，用于鼻腔吹入药代动力学 (PK) 研究。在确定锥形研磨机可将片剂受控研磨至等于或小于 1000 μm 的尺寸范围之前，探索了几种粉碎方法。然而，与盐酸羟考酮速释 (IR) 片剂的最小羟考酮损失相比，研磨导致羟考酮因滥用威慑盐酸羟考酮缓释片而显着损失。研磨的片剂粉末的表征表明，羟考酮的损失不是由于分析程序或高强度研磨过程中羟考酮的相变造成的。当 ER 和 IR 片剂被研磨至等于或低于 500 μm 的粒度分布时，研磨后的片剂粉末中羟考酮的含量均匀度会发生变化，但当颗粒被研磨至高于 500 μm 至等于或低于 1000 μm 时，羟考酮的含量均匀度没有变化。此外，初始赋形剂重量与药物物质的重量比影响从相应制剂中损失的羟考酮的量。然而，溶出度表明，当研磨盐酸羟考酮缓释片时，赋形剂重量与药物物质重量比的差异和研磨片剂的粒度分布不会导致羟考酮释放的显着差异。初始赋形剂重量与药物物质重量比影响从相应制剂中损失的羟考酮的量。然而，溶出度表明，当研磨盐酸羟考酮缓释片时，赋形剂重量与药物物质重量比的差异和研磨片剂的粒度分布不会导致羟考酮释放的显着差异。初始赋形剂重量与药物物质重量比影响从相应制剂中损失的羟考酮的量。然而，溶出度表明，当研磨盐酸羟考酮缓释片时，赋形剂重量与药物物质重量比的差异和研磨片剂的粒度分布不会导致羟考酮释放的显着差异。