An in vitro approach for evaluating the oral abuse deterrence of solid oral extended-release opioids with properties intended to deter abuse via chewing.

The introduction of prescription opioids with abuse-deterrent (AD) properties to the marketplace has created a need for new testing methodologies to evaluate the performance of potentially abuse-deterrent opioid products. Drug abusers may attempt to chew solid oral extended-release (ER) opioids prior to ingestion to bypass the ER mechanism of the formulation to achieve euphoria. In the present study, a chewing apparatus was utilized to develop an in vitro chewing method for Hysingla ER tablets, a prescription opioid with labeling describing abuse deterrence via the oral route when chewed. Simulated chewing of Hysingla resulted in initially faster drug release during chewing while subsequent dissolution testing demonstrated that the masticated tablets still maintained ER properties. The degree of mastication and corresponding drug release were influenced by the compression gap and the resulting chewing forces. Simulated chewing followed by dissolution testing with different strengths of Hysingla indicated similar AD performance across strengths. By contrast, an opioid product with labeling that does not describe abuse-deterrent properties showed lower resistance to chewing resulting in higher drug release. The results of the present study suggest that the chewing methodology evaluated in this work may provide a useful in vitro tool for the comparative evaluation of AD properties.

Effects of Dissolution Medium pH and Simulated Gastrointestinal Contraction on Drug Release From Nifedipine Extended-Release Tablets.

In contrast to nifedipine matrix-based extended-release dosage forms, the osmotic pump drug delivery systems have a zero-order drug release independent of external variables such as pH, agitation rate, and dissolution media. The objective of this study focuses on the in vitro evaluation of the mechanical properties of osmotic pump and polymer matrix-based formulations in dissolution media, and the potential impacts that media pH and simulated gastrointestinal contraction have on drug release. Two strengths of osmotic pump product A and polymer matrix-based product B were used in this study. An in-house system was developed with the capability of applying mechanical compression and monitoring mechanical properties of sample during dissolution testing. A United States Pharmacopeia or an in-house apparatus was used for dissolution testing under various conditions. Compared to the product A, the mechanical properties of the product B change significantly at various pHs and mechanical compressions. The results suggest that polymer matrix-based products bear a risk of formulation-related interactions with the gastrointestinal tract during in vivo drug dissolution, especially in the case of concomitant pH and gastric contractile changes. Modified dissolution testing devices may help formulation scientists in product development and provide regulatory agencies with an additional metric for quality assurance of drug products.

Mixed and Matched Metallo-Nanotexaphyrin for Customizable Biomedical Imaging.

The discovery and synthesis of multifunctional organic building blocks for nanoparticles have remained challenging. Texaphyrin macrocycles are multifunctional, all-organic compounds that possess versatile metal-chelation capabilities and unique theranostics properties for biomedical applications. Unfortunately, there are significant difficulties associated with the synthesis of texaphyrin-based subunits capable of forming nanoparticles. Herein, the detailed synthesis of a texaphyrin-phospholipid building block is reported via a key 1,2-dinitrophenyl-phospholipid intermediate, along with stable chelation of two clinically relevant metal ions into texaphyrin-lipid without compromising their self-assembly into texaphyrin nanoparticles or nanotexaphyrin. A postinsertion methodology to quantitatively insert a variety of metal-ions into preformed nanotexaphyrins is developed and employed to synthesize a structurally stable, mixed 111 indium-manganese-nanotexaphyrin for dual modal single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). In vivo dual SPECT/MRI imaging of 111 In-Mn-nanotexaphyrins in an orthotopic prostatic PC3 mouse model demonstrates complementary signal enhancement in the tumor with both modalities at 22 h post intravenous administration. This result highlights the utility of hybrid metallo-nanotexaphyrins to achieve sensitive and accurate detection of tumors by accommodating multiple imaging modalities. The power of this mixed and matched metallo-nanotexaphyrin strategy can be unleashed to allow a diverse range of multifunctional biomedical imaging.