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Drug abuse has become a global health problem over the past few years. Opioid abuse increased with an increase in the prescription of opioids for pain management. Many other classes of drugs are also abused and misused like anti-depressants, stimulants, hallucinogens, anti-psychotic, and anticholinergic drugs. One of the major reasons is that patients falsely diagnosed with depression, anxiety, and severe pain are prescribed these drugs, which are likely to be addictive. Abuse-deterrent formulations are one means to control drug abuse and overdose of prescription opioids. In this review, we explained how abuse-deterrent technology works, key ingredients used in abuse-deterrent formulations, a brief about marketed opioid drug products with abuse-deterrent properties, and the stand of regulatory agencies in the approval process of opioid drug products. In the end, it summarized that pharmaceutical industries and the FDA put their efforts into reducing drug abuse by encouraging the development of ADFs. Most available drug product having abuse-deterrent features contains Polyethylene oxide, which degrades at high temperatures. It requires the attention of the researcher to find an alternate ingredient or process to overcome said problem. From a regulatory point of view, only a few regulatory agencies have published their guidance on ADFs. It is important to convey other regulatory organizations' perspectives on ADFs as well.

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The misuse and abuse of opioid analgesics continue to pose a serious public health concern, but for some patients, opioids remain an important analgesic option. Extended-release (ER) opioid formulations are effective for treating chronic pain and are supported by multiple 12-week efficacy studies. ER opioids often contain a high opioid content, and similar to immediate-release (IR) formulations, are subject to abuse, misuse, and diversion. Unintentional misuse may also occur when ER formulations are manipulated for medicinal administration, such as crushing a dose for easier oral intake. As part of a multipronged strategy designed to fight the opioid epidemic, abuse-deterrent formulations (ADFs) were developed to deter misuse, abuse, and diversion of opioids by making manipulation more difficult and nonoral routes of administration less rewarding. Although ADF opioids have been shown to decrease rates of abuse and diversion, they are not equally effective in terms of deterring manipulation for abuse or misuse. Xtampza ER utilizes DETERx technology, which allows it to retain ER characteristics when chewed or crushed, making it the only ER opioid without a boxed warning against these types of manipulation. OxyContin was also developed as an ADF but uses RESISTEC technology, making the tablet hard to crush and viscous in aqueous solutions. ADF utilization has been hampered by patient access issues, including high prices due to lack of insurance coverage. Postmarket real-world studies demonstrate lower rates of abuse, misuse, and diversion for ADF ER opioids compared with non-ADF formulations. However, similar studies comparing abuse-related effectiveness and health care costs for ADF opioids are warranted if clinicians are expected to utilize these potentially safer opioid formulations. These studies would support further education surrounding the benefits and utilization of ADFs and manipulation potential of different ADFs.

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Misuse of prescription opioid drugs is the leading cause of the opioid crisis and overdose-related death. Abuse deterrent formulations (ADFs) have been developed to discourage attempts to tamper with the formulation and alter the ingestion methods. However, abusers develop complex extraction strategies to circumvent the ADF technologies. For comprehensive deterrence of drug abuse, we develop tannic acid nanoparticles (NPs) that protect encapsulated opioids from solvent extraction and thermal challenge (crisping), complementing the existing formulation strategy to deter injection abuse. Here, we develop a hybrid ADF tablet (NP-Tab), consisting of iron-crosslinked tannic acid NPs encapsulating thebaine (model opioid compound), xanthan gum, and chitosan (gel-forming polymers), and evaluate its performance in common abuse conditions. NP-Tab tampered by crushing and suspended in aqueous solvents forms an instantaneous gel, which is difficult to pull or push through a 21-gauge needle. NPs insulate the drug from organic solvents, deterring solvent extraction. NPs also promote thermal destruction of the drug to make crisping less rewarding. However, NP-Tab releases thebaine in the simulated gastric fluid without delay, suggesting that its analgesic effect may be unaffected if consumed orally as prescribed. These results demonstrate that NP-Tab can provide comprehensive drug abuse deterrence, resisting aqueous/organic solvent extraction, injection, and crisping, while retaining its therapeutic effect upon regular usage.

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Opioid misuse is a public health crisis in the United States. In response, the FDA has approved drug products with abuse-deterrent features to reduce the risk of prescription opioid abuse. Abuse-deterrent formulations (ADFs) typically employ physical or chemical barriers or incorporate agonist-antagonist combinations as mechanisms to deter misuse. This study aims to assess the impact of abuse-deterrent properties, specifically ion-exchange resin complexation as a chemical barrier, on a model drug, promethazine hydrochloride (PMZ) tablets. Various formulations were developed through twin-screw wet granulation (TSWG) followed by twin-screw melt granulation (TSMG). In the TSWG process, the drug interacts with the resin through an exchange reaction, forming a drug-resin complex. Additionally, the study explored factors influencing the complex formation between the drug and resin, using the drug loading status as an indicator. DSC and ATR studies were carried out to confirm the formation of the drug-resin complex. Subsequently, hot melt granulation was employed to create a matrix tablet incorporating Kollidon® SR and Kollicoat® MAE 100P, thereby enabling sustained release properties. The drug-resin complex embedded in the matrix effectively deters abuse through methods like smoking, snorting, or parenteral injection, unless the drug can be extracted. In order to assess this, solvent extraction studies were conducted using an FDA-recommended solvents, determining the potential for abuse. Further investigations involved dissolution tests in change-over media, confirming the extended-release properties of the formulation. Results from dissolution studies comparing the ground and intact tablets provided positive evidence of the formulation's effectiveness in deterring abuse. Finally, alcohol-induced dose-dumping studies were conducted in compliance with FDA guidelines, concluding that the formulation successfully mitigates dose dumping in the presence of alcohol.

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To combat opioid abuse, the U.S. Food and Drug Administration (FDA) released a comprehensive action plan to address opioid addiction, abuse, and overdose that included increasing the prevalence of abuse-deterrent formulations (ADFs) in opioid tablets. Polyethylene oxide (PEO) has been widely used as an excipient to deter abuse via nasal insufflation. However, changes in abuse patterns have led to unexpected shifts in abuse from the nasal route to intravenous injection. Case reports identify adverse effects similar to thrombotic thrombocytopenic purpura (TTP) syndrome following the intravenous (IV) abuse of opioids containing PEO excipient. Increased risk of IV opioid ADF abuse compared to clinical benefit of the drug led to the removal of one opioid product from the market in 2017. Because many generic drugs containing PEO are still in development, there is interest in assessing safety consistent with generic drug regulation and unintended uses. Currently, there are no guidelines or in vitro assessment tools to characterize the safety of PEO excipients taken via intravenous injection. To create a more robust excipient safety evaluation tool and to study the mechanistic basis of HMW PEO-induced TMA, a dynamic in vitro test system involving blood flow through a needle model has been developed.

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INTRODUCTION: The 2010 release of an abuse deterrent formulation (ADF) of OxyContin, a brand name prescription opioid, has been cited as a major driver for the reduction in prescription drug misuse and the associated increasing illicit opioid use and overdose rates. However, studies of this topic often do not account for changes in supplies of other prescription opioids that were widely prescribed before and after the ADF OxyContin release, including generic oxycodone formulations and hydrocodone. We therefore sought to compare the impact of the ADF OxyContin release to that of decreasing prescription opioid supplies in West Virginia (WV). METHODS: Opioid tablet shipment and overdose data were extracted from The Washington Post ARCOS (2006-2014) and the WV Forensic Drug Database (2005-2020), respectively. Locally estimated scatterplot smoothing (LOESS) was used to estimate the point when shipments of prescription opioids to WV began decreasing, measured via dosage units and morphine milligram equivalents (MMEs). Interrupted time series analysis (ITSA) was used to compare the impact LOESS-identified prescription supply changes and the ADF OxyContin release had on prescription (oxycodone and hydrocodone) and illicit (heroin, fentanyl, and fentanyl analogues) opioid overdose deaths in WV. Model fit was compared using Akaike Information Criteria (AIC). RESULTS: The majority of opioid tablets shipped to WV from 2006 to 2014 were generic oxycodone or hydrocodone, not OxyContin. After accounting for a 6-month lag from ITSA models using the LOESS-identified change in prescription opioid shipments measured via dosage units (2011 Q3) resulted in the lowest AIC for both prescription (AIC = -188.6) and illicit opioid-involved overdoses (AIC = -189.4), indicating this intervention start date resulted in the preferred model. The second lowest AIC was for models using the ADF OxyContin release as an intervention start date. DISCUSSION: We found that illicit opioid overdoses in WV began increasing closer to when prescription opioid shipments to the state began decreasing, not when the ADF OxyContin release occurred. Similarly, the majority of opioid tablets shipped to the state for 2006-2014 were generic oxycodone or hydrocodone. This may indicate that diminishing prescription supplies had a larger impact on opioid overdose patterns than the ADF OxyContin release in WV.

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OBJECTIVE: We offer an overview of ADHD research using mouse models of nicotine exposure. METHOD: Nicotine exposure of C57BL/6 or Swiss Webster mice occurred during prenatal period only or during the prenatal and the pre-weaning periods. Behavioral, neuroanatomical and neurotransmitter assays were used to investigate neurobiological mechanisms of ADHD and discover candidate ADHD medications. RESULTS: Our studies show that norbinaltorphimine, a selective kappa opioid receptor antagonist is a candidate novel non-stimulant ADHD treatment and that a combination of methylphenidate and naltrexone has abuse deterrent potential with therapeutic benefits for ADHD. Other studies showed transgenerational transmission of ADHD-associated behavioral traits and demonstrated that interactions between untreated ADHD and repeated mild traumatic brain injury produced behavioral traits not associated with either condition alone. CONCLUSION: Preclinical models contribute to novel insights into ADHD neurobiology and are valuable tools for drug discovery and translation to benefit humans with ADHD.

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Chronic pain is a byproduct of many diseases and conditions. Along with long-term opioid medication use in chronic pain management, misuse of this vital medication has been a topic of much debate over the last two decades. Abuse-deterrent formulations play a critical role in comprehensive opioid risk management strategies, limiting the attractiveness and drug-liking qualities of an opioid drug by limiting their bioavailability, making abuse of the tampered opioid medication less appealing or rewarding, or impeding the extraction of the opioid drug and thus impeding the administration of the opioid formulation via alternative routes. The present article covers various regulatory actions, expectations in abuse-deterrent formulation approval, and emerging opioid abuse-deterrent formulation strategies, such as incorporating physical barriers, chemical barriers, aversion agents, pH modulating release properties, novel delivery systems, agonist/antagonist combinations, and prodrugs, as potential approaches to encountering the crisis of the opioid abuse epidemic. Looking at the severity of the opioid crisis across the globe now is the right time for various regulatory agencies to come under one roof to save society from the opioid epidemic, define the policy on how and when to prescribe opioid formulations to patients, perform abuse risk assessments, and make more efforts to approve only abusedeterrent opioid medication.

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Abuse-deterrent formulations (ADFs) refer to formulation technologies aiming to deter the abuse of prescription drugs by making the dosage forms difficult to manipulate or extract the opioids. Assessments are required to evaluate the performance of the drugs through different routes including injection, ingestion, and insufflation and also when the drugs are manipulated. Chewing is the easiest and most convenient way to manipulate the drugs and deserves investigation. Chewing is one of the most complex bioprocesses, where the ingested materials are subject to periodic tooth crushing, mixed through the tongue, and lubricated and softened by the saliva. Inter- and intra-subject variations in chewing patterns may result in different chewing performances. The purpose of this study is to use a chewing simulator to assess the deterrent properties of tablets made of polyethylene oxide (PEO). The simulator can mimic human molar grinding with variable chewing parameters including molar trajectory, chewing frequency, and saliva flow rate. To investigate the effects of these parameters, the sizes of the chewed tablet particles and the chewing force were measured to evaluate the chewing performance. Thirty-four out of forty tablets were broken into pieces. The results suggested that the simulator can chew the tablets into smaller particles and that the molar trajectory and saliva flow rate had significant effect on reducing the size of the particles by analysis of variance (ANOVA) while the effect of chewing frequency was not clear. Additionally, chewing force can work as an indicator of the chewing performance.

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Aims: Xtampza® ER (Collegium Pharmaceutical, MA, USA) is an abuse-deterrent formulation (ADF) of oxycodone intended to deter tampering for use by unintended routes of administration. We assessed whether Xtampza ER exposures were less likely to result in severe medical outcomes relative to other opioid analgesic exposures. Materials & methods: Exposures reported to participating poison centers between 2016 and 2021 inclusive that were followed to a known medical outcome were analyzed. Xtampza ER was compared with other ADF opioids, non-ADF extended-release opioids, single-entity oxycodone immediate-release, unspecified oxycodone and unspecified morphine. Results & conclusion: No Xtampza ER exposures involved unintended routes of administration. Xtampza ER exposures were less likely to be abuse, misuse or suspected suicidal, and medical outcomes were less severe than comparators.

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High molar mass polyethylene oxide (HM-PEO) is commonly used to enhance the mechanical strength of solid oral opioid drug products to deter abuse. Because the properties of PEO depend on molar mass distribution, accurately determining the molar mass distribution is a necessary part of understanding PEO's role in abuse-deterrent formulations (ADF). In this study, an asymmetrical flow field-flow fractionation (AF4) analytical procedure was developed to characterize PEO polymers with nominal molar masses of 1, 4 or 7 MDa as well as those from in-house prepared placebo ADF. The placebo ADF were manufactured using direct compress or hot-melt-extrusion methods, and subjected to physical manipulation, such as heating and grinding before measurement by AF4 were performed. The molar mass distribution characterized by AF4 revealed that PEO was sensitive to thermal stress, exhibiting decreased molar mass with increased heat exposure. The optimized AF4 method was deemed suitable for characterizing HM-PEO, offering adequate dynamic separation range for PEO with molar mass from 100 kDa to approximately 10 MDa.

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OBJECTIVE: Original brand extended-release (ER) oxycodone tablets (OC) for oral use were reformulated (ORF) with abuse-deterrent properties (ADP) against inhalation and injection routes in August 2010. This product transition provided an opportunity to compare "before and after" reformulation abuse trends. Our goal was to assess the change in abuse of brand oxycodone ER from before and after introduction of ORF. METHODS: Change in self-reported non-oral "OxyContin" abuse in the previous 30 days during two years pre- and four years post-reformulation was assessed among adults evaluated for substance use and treatment planning using the Addiction Severity Index-Multimedia Version (ASI-MV). Comparator opioids were used to provide a frame of reference for changes in abuse due to competing population-level opioid abuse interventions and other factors unrelated to the reformulation. A proportion (PR) and abuse report dispensing ratio (ARDR) are reported because a single measure of abuse has not been identified that can optimally describe opioid abuse or changes in opioid abuse. RESULTS: Interrupted time-series analyses indicated an immediate decline in non-oral abuse measures post-reformulation (PR = -52.1%; ARDR = -32.2%). Significant decreases from pre- to post-reformulation in non-oral abuse overall were observed (PR [95% CI] = -30.7% [-46.9%, -9.5%]; ARDR = -29.3% [-37.5%, -20.1%]). Comparator opioids did not demonstrate similar trends over the period. CONCLUSIONS: Methodology applied in this study suitably assessed the effectiveness of an ADP product. Among individuals assessed for substance use, a differential decline in non-oral abuse of brand ER oxycodone was observed since introduction of ORF.

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Although opioids are useful narcotic analgesics in clinical settings, their misuse and addiction in the United States of America and other countries are rapidly increasing. Therefore, the development of abuse-deterrent formulations is an urgent issue. We herein investigated how to select the ratio of an opioid and the opioid receptor antagonist, naloxone in abuse-deterrent formulations for mice. The conditioned place preference (CPP) test was used to evaluate the rewarding effects of abused drugs. The opioids morphine (30 µmol/kg), oxycodone (3 µmol/kg), fentanyl (0.4 µmol/kg), and buprenorphine (0.5 µmol/kg) significantly induced place preference in mice. We also examined the optimal ratio of naloxone and opioids to inhibit the rewarding effects of the latter. Naloxone (3-5 µmol/kg) effectively inhibited place preference induced by the opioids tested. We calculated theoretical drug doses that exerted the same pharmacodynamic effects based on two parameters: µ-opioid receptor binding affinity and blood-brain barrier (BBB) permeability. Theoretical doses were very close to the drug doses at which mice showed place preference. Therefore, the CPP test is useful as a behavioral method for evaluating abuse-deterrent formulations of opioids mixed with an antagonist. The ratio of naloxone with opioids, at which mice did not show place preference, may be an effective index for developing abuse-deterrent formulations. Ratios may be calculated for other opioids based on µ-opioid receptor binding affinity and BBB permeability.

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Opioid medications play a vital role in treating moderate to severe pain. Unfortunately, many drug misusers and abusers attempt to alter the formulations or properties of these drugs by manipulation, (e.g., crushing, chewing, smoking, snorting, injecting). The intravenous (IV) route is most dangerous to abusers, as the drugs directly enter the circulatory system and produce intense euphoria. To obtain a full understanding of the impact of syringe factors (e.g., needle gauge size, needle length, syringe barrel size), on the ease of injection, we undertook a comprehensive assessment of syringeability and injectability of manipulated abuse-deterrent formulations (ADFs). A texture analyzer-based testing method was developed for the measurement of the resistance force of pulling, holding, and pushing phases of injections. Results showed that the finer needle gauge sizes required higher injection force to withdraw drug solutions. In addition, the syringed liquid volume was highly dependent on needle gauge size, holding time, and sample viscosity. In most cases, a lower needle gauge number and a longer holding time increased the syringed volume. Needle length was highly correlated to injection force (R2 = 0.99). Using longer needles to inject drug solution requires greater force. Furthermore, large barrel size was correlated to pushing force (R2 = 0.99); thus, increasing the difficulty of pushing the plunger of a large syringe with one hand. Finally, relationships between injection force, sample viscosity, and testing conditions were elucidated using a mathematical model, which could be used in the future to assess and predict injection force of solution samples.

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Intravenous administration of abuse-deterrent opioid products poses high safety risks, in part due to the presence of high molecular weight polymeric excipients. Previous in vivo studies in animal models have shown that the higher molecular weight (Mw) polymeric excipients like polyethylene oxide (PEO) were directly linked to such adverse responses as intravenous hemolysis and kidney damage. PEO polymers have been widely used in abuse-deterrent formulations (ADF) of opioid products, adding to concerns over the general safety of the opioid category due to the unknown safety risk from abuse via unintended routes. The current study focused on the determination of the critical overlap concentration (c*) at various PEO molecular weights to aid in explaining differences in observed adverse responses from previous animal studies on the intravenous administration of PEO solutions. Adverse in vivo responses may be related to the viscoelastic regime of the polymer solution, which depends not only on Mw but also on concentration. Having a localized polymer concentration in the blood above the c*, i.e., the transition from the dilute to semi-dilute entangled viscoelastic regime, may influence the flow behavior and interactions of cells in the blood. The relationship of c* to this combination of physical, chemical, and rheological effects is a possible driving force behind adverse in vivo responses.

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El consumo de analgésicos opioides ha experimentado un vertiginoso ascenso en las últimas décadas a nivel mundial. Este elevado consumo está relacionado con el aumento del número de prescripciones de opioides para el tratamiento del dolor crónico y por el aumento de la dependencia a opioides. Los analgésicos opioides tienen una corta duración de acción, siendo necesarias múltiples administraciones para obtener analgesia prolongada. El empleo de formulaciones de liberación prolongada permite espaciar los intervalos posológicos y estabilizar las concentraciones máximas de fármaco en sangre, favoreciendo el cumplimiento terapéutico y reduciendo el riesgo de desarrollar adicción. Sin embargo, estas formulaciones llevan dosis más altas de analgésicos opioides que las hacen más susceptibles de ser alteradas. Así, los avances en tecnología farmacéutica más recientes se han orientado hacia la aplicación de recursos tecnológicos disuasorios de su utilización por vías de administración alternativas con fines no terapéuticos. A su vez, los sistemas de liberación modificada también juegan un papel esencial en el tratamiento de la adicción a opioides: con el desarrollo de sistemas de administración parenteral capaces de prolongar la liberación de opioides durante meses se consigue superar una de las mayores dificultades para alcanzar el éxito del tratamiento en este tipo de pacientes como es el cumplimiento terapéutico. En este artículo se realiza una revisión bibliográfica de los diferentes sistemas de liberación prolongada de opioides que se encuentran actualmente autorizados en Europa y/o en Estados Unidos para el tratamiento del dolor y de la dependencia a opioides. (AU)

The consumption of opioid analgesics has increased drastically in the last decades worldwide. This high consumption is linked with a surge in the number of opioid prescriptions for the treatment of chronic pain and a surge in opioid misuse and addiction. Opioid analgesics have a short duration of action, making necessary frequent administrations to provide extended analgesia. The use of prolonged-release formulations enables dosing intervals to be spaced out and drug blood levels to be stabilized, improving therapeutic compliance, and reducing the likelihood of developing addiction. However, these formulations contain higher doses of opioid analgesics which make them more susceptible to be manipulated. Hence, the most recent advances in pharmaceutical technology have been oriented towards the application of abuse deterrent technologies aiming to prevent their administration through alternative routes. Moreover, prolonged- release systems also play an essential role in the treatment of opioid addictions with the development of parenteral dosage forms capable of prolonging opioid release for months that help overcome one of the most important drawbacks in achieving treatment success, namely, patient compliance. We review herein the different prolonged-release opioid dosage forms currently approved in Europe and/or the United States for the treatment of pain and opioid dependence. (AU)

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PURPOSE OF REVIEW: Appropriate use of opioid analgesics is a key concern within the field of pain medicine. Several methods exist to discourage abuse and facilitate effective treatment regimens. Pill counting is often cited as one such method and frequently employed in varying fashions within clinical practice. However, to date, there is no published review of the evidence to support this practice. This was a comprehensive review of the available literature that was conducted with analysis of the efficacy and practical application of pill counting during treatment of chronic pain conditions. RECENT FINDINGS: There is paucity in data regarding pill count importance in pain management. Pill count is a very important tool to monitor compliance of opioids use which in turn can prevent several complications associated with opioid misuse. Pill counting may be used in conjunction with other abuse deterrents, although increased support for this practice requires standardized methods of pill counting and further analysis of its effectiveness.

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Introduction: Poly(ethylene oxide) (PEO) is the most common polymer used in commercial abuse-deterrent tablets. Due to its vulnerability to high-temperature manipulation, we investigated abuse-deterrent capability and the toxicity of this polymer upon thermal treatments at 80°C and 180°C for 1 hour. Methods: Tablets (200 mg PEO and 300 mg Avicel®) were directly compressed under 2000 lb. The thermally manipulated PEOs were evaluated for their viscosity, crushability, structural changes, and cell toxicity. Results: Our findings showed that 180°C-treated tablets underwent some degrees of oxidative degradation with profound toxicity in both mesenchymal stem cells and MG63 cells. The 180°C-treated tablets exhibited almost no resistance against crushing and were prone to abuse. While thermal processing of PEO at around its melting temperature is a common approach to enhance crush resistance of its dosage forms, thermal manipulation at close to the PEO's oxidation temperature can lead to structural changes, dramatic loss of crush and extraction resistance, and significant cell toxicity. Conclusion: Similar to the low molecular weight PEO, when thermally manipulated at its thermo-oxidative temperature, the high molecular weight PEO loses its deterrence performance and causes severe cell toxicity.

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Pharmaceutical opioid dosage forms are commonly misused via an oral route in non-manipulated form, i.e., overdose in intact form, or manipulated form, i.e., after crushing the dosage form, and also via the non-oral route in manipulated form, particularly the parenteral or nasal route. To assess the self-regulated anti-overdose property, crushing strength, extractability, and syringeability of the developed drug delivery system by in vitro laboratory studies. Tapentadol HCl drug particulates fabricated using different polymers were assessed for extractability studies in 25 ml of water at room temperature (RT) and at > 90°C. Crushing strength was assessed by grinding the drug particulates in a mortar and pestle and a coffee grinder for 1 min. For syringeability, an attempt was made to withdraw the drug mixture using a 1 ml insulin syringe for 1 min. To assess the self-regulated anti-overdose property, in vitro dissolution testing on a single-capsule per dissolution vessel (normal condition) and four-capsules per dissolution vessel (overdose condition) was performed. POLYOX, Natrosol, and Blanose-containing drug particles retarded drug extraction by > 80% at RT and > 90°C. After 1 min of grinding in a mortar and pestle and a coffee grinder, crushed POLYOX-containing drug particulates were retained at > 99% on the ASTM-170# screen. The attempt to withdraw the viscous mixture of drug formulation prepared with 5 ml of water for 1 min using a 1 ml insulin syringe was unsuccessful. In dissolution studies, more than 90% of the drug was released in normal conditions, and more than 90% of the drug was retarded in overdose conditions. In vitro laboratory studies demonstrate that the developed self-regulated anti-overdose crush-resistant drug delivery system may deter misuse via oral and non-oral routes.

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Opioids are commonly prescribed across the United States (US) for pain relief, despite their highly addictive nature that often leads to abuse and overdose deaths. Abuse deterrent formulations (ADFs) for prescription opioids make the non-therapeutic use of these drugs more difficult and less satisfying. Although approximately one-third of surveyed abusers in the US reported smoking opioids, to our knowledge, no commercialized ADF effectively prevents opioid smoking. Here, we report a novel approach to deter smoking of a model prescription opioid drug, thebaine (THB), by using polymer blend microspheres (MS) comprising polylactic acid (PLA) and polycaprolactone (PCL). We utilized high-performance liquid chromatography (HPLC) and thermogravimetric analysis (TGA) to test the ability of PLA-PCL MS to limit the escape of vaporized THB. Additionally, we compared the abuse-deterrent potential of PLA-PCL MS to that of activated carbon (AC) and mesoporous silica (MPS), two materials with excellent drug-adsorbing properties. Our MS formulation was effective in reducing the amount of both active drug and thermal degradation products in the vapor generated upon heating of THB. These results support that PLA-PCL microspheres can be co-formulated in a tablet with common prescription opioids to deter their abuse via the smoking route.

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