Oxycodone Hydrochloride/Niacin

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.

Concomitant intake of alcoholic beverages with sustained-release oral formulations may potentially lead to dose dumping. Alcohol-resistance testing is currently a requirement for the manufacturers by regulatory authorities. Silk fibroin produced by silkworm Bombyx mori is suggested in this work as a potential alternative to a narrow spectrum of alcohol-resistant excipients. Oxycodone HCl, tramadol HCl, and flurbiprofen were selected as model drugs and formulated with regenerated silk fibroin either in the form of an amorphous solid dispersion or as a physical mixture and compressed into tablets. Preliminary compactability and tampering-resistance studies were performed. The ethanol-resistance was tested in media containing 5%, 10%, 20%, or 40% (v/v) ethanol concentration. Drug release profiles were compared using f₂ similarity factor. Good mechanical tampering-resistance (tensile strength of 14.6 MPa at 400 MPa compression pressure) was obtained for tablets compressed from physical mixture. Tablets compressed from amorphous solid dispersion had lower tensile strength (2.2 MPa) but showed chemical tampering-resistance to extraction by pure ethanol (7.1% of oxycodone HCl after 24 h). Drug release is controlled predominantly by swelling and diffusion. With an increasing ethanol concentration in release medium, the tablets swelled less, resulting in a slower release. This trend was similar for all tested drugs and for both physical states formulations. No dose dumping occurred in the presence of ethanol; therefore, silk fibroin could be considered as an alternative alcohol-resistant excipient for sustained release application.