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.
Keywords: dissolution; drug loss; milling; opioids; polyethylene oxide (PEO).
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