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2.
AAPS PharmSciTech ; 21(3): 99, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32133549

RESUMO

The objective of the present investigation was to understand the effect of sucrose acetate isobutyrate (SAIB) on abuse-deterrent properties (ADPs) of abuse-deterrent formulations (ADFs) based on Polyox™. SAIB would enhance ADPs of Polyox™-based formulations due to its glassy liquid and hydrophobic properties. Formulations were prepared by granulation followed by compression and heat curing at 90°C. The formulations were evaluated for surface morphology, hardness, manipulation in coffee grinder, particle size distribution, drug (pseudoephedrine hydrochloride) extraction in water, alcohol, 0.1 N HCl, 0.1 N NaOH at room temperature and elevated temperature using microwave and oven, syringeability and injectability, and dissolution. The heat curing of formulations significantly increased the hardness (> 490 N). Addition of SAIB imparted elasticity to formulations and decreased brittleness as indicated by lower values of work done and gradient compared to control formulations. After grinding, about 7.7-25.6% of the powder remained on the sieve (1 mm pore opening), D90 was 53.1-136.7 µm more, and Q (fraction < 500 µm) was 17.8-40.7% less in SAIB-based formulations compared to control formulations. Drug extraction between control and test intact formulations was similar. However, drug extraction was 23.9-42.5% (water), 20.6-26.1% (0.1 N HCl), and 37.4-50.6% (0.1 N NaOH) less in SAIB-based powder cured and uncured formulations compared to control formulations. Dissolution varied from 65.6 ± 4.2 to 97.6 ± 4.0% in 9 h from the formulations. In conclusion, addition of SAIB to Polyox™-based ADFs has synergistic effect on ADPs. This would further decrease potential of drug abuse/misuse by various routes.


Assuntos
Formulações de Dissuasão de Abuso/métodos , Composição de Medicamentos/métodos , Desenvolvimento de Medicamentos/métodos , Sacarose/análogos & derivados , Formulações de Dissuasão de Abuso/tendências , Composição de Medicamentos/tendências , Desenvolvimento de Medicamentos/tendências , Dureza , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/metabolismo , Tamanho da Partícula , Pós , Sacarose/administração & dosagem , Sacarose/química , Difração de Raios X/métodos , Difração de Raios X/tendências
4.
AAPS PharmSciTech ; 21(2): 40, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897805

RESUMO

There is a need to develop in vitro dissolution methods that discriminate for particle size of the manipulated abuse deterrent formulation (ADF) and that can be used for in vivo predictive models since dissolution methods developed for intact formulation might not be suitable for manipulated ones. A vertical diffusion cell (VDC) and United States Pharmacopeia (USP) Apparatus 1, 2, and 4 were evaluated for measuring the dissolution of intact and manipulated metoprolol succinate tablets with abuse deterrent-like properties. These tablets were physically manipulated to produce fine (106-500 µm) and coarse (500-1000 µm) powder samples. The VDC method was not able to discriminate the effect of particle size on drug release with varied stirring rate (200 to 800 rpm), molecular weight cut-off (MWCO, 3-5 kDa to 12-14 kDa) of the diffusion membrane, or composition and ionic strength (0.45% and 0.9%) of receiver medium. Standard and modified USP Apparatus 1 and 2 methods were assessed; however, large variations (RSD > 20%) were observed with USP Apparatus 1 for manipulated product dissolution and floating powder samples caused failure of auto-sampling when using standard USP Apparatus 2. For the USP Apparatus 4 dissolution method, packing configuration (1, 3, 8 layers and blend), ionic strength of dissolution medium (0.017, 0.077, and 0.154 M additional NaCl), and flow rate (4, 8, 16 mL/min) were studied to discriminate the effect of particle size on release. The USP Apparatus 4 dissolution method was optimized by using a packaging configuration of 8 layers with 8 mL/min flow rate which exhibited low variability and complete drug release and it could be used for in vivo predictive models. The dissolution method variables can be optimized for a specific product for desirable reproducibility and discriminatory power when using USP Apparatus 4.


Assuntos
Formulações de Dissuasão de Abuso , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Uso Indevido de Medicamentos sob Prescrição/prevenção & controle , Difusão , Metoprolol/administração & dosagem , Metoprolol/química , Modelos Teóricos , Peso Molecular , Tamanho da Partícula , Pós , Solubilidade , Comprimidos
5.
Expert Opin Drug Metab Toxicol ; 16(2): 125-141, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31976778

RESUMO

Introduction: Opioids continue to be used widely for pain management. Widespread availability of prescription opioids has led to opioid abuse and addiction. Besides steps to reduce inappropriate prescribing, exploiting opioid pharmacology to make their use safer is important.Areas covered: This article discusses the pathology and factors underlying opioid abuse. Pharmacokinetic and pharmacodynamic properties affecting abuse liability of commonly abused opioids have been highlighted. These properties inform the development of ideal abuse deterrent products. Mechanisms and cost-effectiveness of available abuse deterrent products have been reviewed in addition to the pharmacology of medications used to treat addiction.Expert opinion: The opioid crisis presents unique challenges to managing pain effectively given the limited repertoire of strong analgesics. The 5-point strategy to combat the opioid crisis calls for better preventive, treatment, and recovery services, better data, better pain management, better availability of overdose-reversing drugs and better research. There is an urgent need to decrease the cost of abuse deterrent opioids which deters their cost-effectiveness. In addition, discovery of novel analgesics, further insight into central and peripheral pain mechanisms, understanding genomic risk profiles for efficient targeted efforts, and education will be key to winning this fight against the opioid crisis.


Assuntos
Analgésicos Opioides/administração & dosagem , Epidemia de Opioides/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Formulações de Dissuasão de Abuso , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/economia , Animais , Análise Custo-Benefício , Overdose de Drogas/tratamento farmacológico , Humanos , Prescrição Inadequada/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Dor/tratamento farmacológico
6.
Int J Pharm ; 577: 119042, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31953084

RESUMO

Prescription opioids have widely been abused as an epidemic. In this research, we developed a drug composition based on the crosslinked carboxymethylcellulose (XCMC) and a drug model that can effectively deter abuse by injection via multiple mechanisms. The anionic nature of the XCMC is responsible for complexing the cationic opioids in aqueous solutions, minimizing the free drug amount accessible for extraction. The crosslinked nature of the polymer is responsible for its swelling and partial containment of the drug solution within the swollen polymer's network, thus minimizing the available volume for subsequent injection. We have shown that XCMC can efficiently interact with cationic drugs in the form of physical blends and chemical complexes in different aqueous solvents, forming abuse-deterrent complexes. The complexation efficiency was affected by the solution pH and ionic strength, as well as the drug to polymer ratio in the formulation. The in vitro dissolution studies were conducted in two stages, the stage I in 0.1 M HCl and the stage II in water and pH 7.5 phosphate buffer. These studies confirmed the proper drug release under the legitimate conditions of use. Therefore, the XCMC polymers have a great potential to be used as deterring agents in developing opioid medications with abuse-deterrent properties.


Assuntos
Formulações de Dissuasão de Abuso/métodos , Analgésicos Opioides/administração & dosagem , Carboximetilcelulose Sódica/química , Analgésicos Opioides/química , Química Farmacêutica , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Concentração Osmolar , Solventes/química , Abuso de Substâncias por Via Intravenosa/prevenção & controle
7.
AAPS PharmSciTech ; 21(3): 86, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31997096

RESUMO

The main goal of the presented work was to understand changes in the microstructure of tablets, as well as the properties of its main component viz. polyethylene oxide (PEO) as a function of sintering. Key polymer variables and sintering conditions were investigated, and sintering-induced increase in tablet tensile strength was evaluated. For the current study, binary-component placebo tablets comprised of varying ratios of PEO and anhydrous dibasic calcium phosphate (DCP) were prepared at two levels of tablet solid fraction. The prepared tablets were sintered in an oven at 80°C at different time points ranging from 10 to 900 min and were evaluated for pore size, tablet expansion (%), and PEO crystallinity. The results showed that for efficient sintering and a significant increase in the tablet tensile strength, a minimum of 50% w/w PEO was required. Moreover, all microstructural changes in tablets were found to occur within 60 min of sintering, with no significant changes occurring thereafter. Sintering also resulted in a decrease in PEO crystallinity, causing changes in polymer ductility. These changes in PEO ductility resulted in tablets with higher tensile strength. Formulation variables such as PEO level and PEO particle size distribution were found to be important influencers of the sintering process. Additionally, tablets with high initial solid fraction and sintering duration of 60 min were found to be optimal conditions for efficient sintering of PEO-based compacts. Finally, prolonged sintering times were not found to provide any additional benefits in terms of abuse-deterrent properties.


Assuntos
Formulações de Dissuasão de Abuso , Polietilenoglicóis/química , Comprimidos/química , Resistência à Tração
8.
Int J Pharm ; 569: 118602, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394182

RESUMO

An innovative abuse-deterrent composition was developed to deter the most dangerous route of drug abuse, the intravenous route. The composition is based on a crosslinked sodium starch glycolate (X-SSG) that can effectively complex with cationic drugs in aqueous solutions and minimize the amount of the free drug available for extraction. Furthermore, the crosslinked polymer swells in and entraps a portion of the drug solution by which it reduces the available volume for syringing and subsequent injection. Two deterrent compositions were prepared, a drug-polymer physical blend and a drug-polymer chemical complex. The composition in its complexed form showed greater deterrence capacity than the physical blend except in solvents with ionic moieties, where the deterrence remained almost the same. The studies revealed that the complexation with the drug played a major role in total drug entrapment. Tablets prepared from the drug-polymer complex showed a complete and immediate drug release in 0.1 N HCl within the first 15 min. Moreover, the dissolution studies in the simulated intestinal media ruled out the re-complexation potential between the drug and the polymer. The proposed X-SSG composition provides a desirable drug release in the gastric and intestinal media under the legitimate use while deterring an intravenous abuse.


Assuntos
Formulações de Dissuasão de Abuso , Amido/análogos & derivados , Liberação Controlada de Fármacos , Suco Gástrico/química , Secreções Intestinais/química , Amido/química , Comprimidos
9.
Int J Pharm ; 569: 118629, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31425818

RESUMO

Loperamide, an over the counter anti-diarrheal drug, also infamously referred to as "poor man's methadone". Due to the ease of availability and low price, people/patients abuse it by consuming more than 30 tablets to achieve euphoric effect and to combat opioid withdrawal. But supratherapeutic doses of loperamide result in severe respiratory depression, cardiac dysrhythmia and mortality. To address this issue, we developed a unique and innovative technology to deter multi-dose oral abuse. The concept is to design a tablet which can immediate release loperamide in diarrheic patients (single tablet) while stops loperamide release in case of intentional multi-dose ingestion. Loperamide was molecularly dispersed into gastric soluble cationic polymers - Eudragit® EPO and Kollicoat® Smartseal 100P using hot melt extrusion to obtain filament. Filaments were milled and compressed into tablets ((Eudragit® EPO (SJU1) and Kollicoat® Smartseal (SJU2)) with optimized amount of L-Arginine. Dissolution in 250 mL of Fasted state simulated gastric fluid (FaSSGF) revealed that single tablet of Imodium® (marketed formulation) and SJU1 showed >85% of release within 15 min. Most importantly, in multi-unit dissolution (15 tablets), Imodium® exhibited >90% release but SJU tablets showed <2% of drug release thus demonstrating its ability to deter multi-dose oral abuse.


Assuntos
Formulações de Dissuasão de Abuso , Antidiarreicos/química , Loperamida/química , Administração Oral , Composição de Medicamentos , Liberação Controlada de Fármacos , Tecnologia de Extrusão por Fusão a Quente , Concentração de Íons de Hidrogênio , Comprimidos
11.
Adv Ther ; 36(9): 2394-2401, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31278694

RESUMO

INTRODUCTION: Food can alter the pharmacokinetics of certain abuse-deterrent formulations. Morphine ARER is an oral abuse-deterrent formulation of ER morphine sulfate tablets formulated with physical and chemical properties that contribute to the abuse-deterrent aspects of the drug. This study compared the relative bioavailability of Morphine ARER in the presence and absence of food. METHODS: This was a randomized, single-dose, two-treatment, crossover study in which healthy adults received Morphine ARER 100 mg under fasting and fed conditions. Subjects were given naltrexone 50 mg to limit opioid effects. Plasma concentrations of morphine and its active metabolite morphine-6-glucuronide (M6G) were obtained up to 48 h post-dose; area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUC0-∞), maximum observed plasma concentration (Cmax) and time to Cmax (Tmax) were calculated. Safety was evaluated by observation or report of adverse events, which were monitored during the treatment periods. RESULTS: Of 28 enrolled subjects, 27 completed all treatments; 1 subject in the fasted group withdrew voluntarily. Under fed conditions, the Cmax for morphine was 33% higher (44.78 vs. 33.30 ng/ml for fed and fasted conditions, respectively) and the median Tmax was 30 min longer than under fasted conditions. The overall morphine exposure (AUC0-∞) was similar for fed (440.6 ng · h/ml) vs. fasted conditions (395.1 ng · h/ml). For M6G, the Cmax and AUC0-∞ were similar under both conditions, and the median Tmax for M6G was 60 min longer under fed conditions. Common adverse events were somnolence and nausea. CONCLUSION: Morphine ARER can be administered without regard to food. Plain language summary available for this article. FUNDING: Inspirion Delivery Sciences, LLC.


Assuntos
Analgésicos Opioides/farmacocinética , Derivados da Morfina/farmacocinética , Morfina/farmacocinética , Naltrexona/farmacocinética , Formulações de Dissuasão de Abuso , Adulto , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/sangue , Área Sob a Curva , Disponibilidade Biológica , Estudos Cross-Over , Preparações de Ação Retardada/farmacocinética , Jejum/sangue , Feminino , Interações Alimento-Droga , Humanos , Masculino , Morfina/administração & dosagem , Morfina/sangue , Derivados da Morfina/sangue , Naltrexona/administração & dosagem , Naltrexona/sangue , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/sangue , Antagonistas de Entorpecentes/farmacocinética , Período Pós-Prandial
12.
Regul Toxicol Pharmacol ; 108: 104433, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31362032

RESUMO

PF614, a novel trypsin activated abuse protection (TAAP) prodrug of oxycodone, is being studied as chronic pain analgesic with extended release and abuse resistant properties. A series of nonclinical safety studies were conducted to support PF614 introduction to clinical trials. Ames assays (PF614 and its metabolites), comet assay (PF614 ≤ 50 mg/kg/day oral gavage in rats) and micronucleus assay (PF614 ≤ 175 mg/kg/day oral gavage in rats) were negative. hERG assay IC50 for PF614 was ≥300 µM. PF614 (0.1 and 10 µM) showed a low permeability in Caco-2 cells (≤1.17 x 10-6 cm/s) and was not a P-gp or BCRP substrate or inhibitor. The mean percent unbound PF614 among all concentrations in plasma ranged from 91.2 to 98.4, 79.4 to 100, and 52.9-79.9% in rat, dog, and human, respectively. Also, PF614 was metabolically stable in rat, dog, and human hepatocytes with no metabolites identified. Safety pharmacology study in dog indicated moderately lower heart rate at ≥ 2 mg/kg oral gavage doses. Toxicity studies of PF614 in rat and dog with daily oral doses of 25 and 18 mg/kg, respectively, for 14 Days were well tolerated with favorable safety profile supporting its further clinical evaluation.


Assuntos
Formulações de Dissuasão de Abuso , Analgésicos Opioides/toxicidade , Oxicodona/toxicidade , Pró-Fármacos/toxicidade , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Células CACO-2 , Cães , Eletrocardiografia/efeitos dos fármacos , Feminino , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Masculino , Testes de Mutagenicidade , Proteínas de Neoplasias/metabolismo , Ratos , Regulador Transcricional ERG/metabolismo , Tripsina
13.
Value Health ; 22(4): 416-422, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30975392

RESUMO

OBJECTIVE: Opioid abuse is a significant public health problem in the United States. We evaluate the clinical effectiveness and economic impact of abuse-deterrent formulations (ADF) of opioids relative to non-ADF opioids in preventing abuse. METHODS: We developed a cost-effectiveness model simulating 2 cohorts of 100 000 noncancer, chronic-pain patients newly prescribed either ADF or non-ADF extended-release (ER) opioids and followed them over 5 years, tracking new events of opioid abuse and opioid-related overdose deaths in addition to tracking 5-year cumulative costs of therapeutic use and abuse of ADF and non-ADF opioids. Patients in each cohort entered the model for therapeutic opioid use from where they could continue in that pathway, discontinue opioid use, or abuse opioids or die of opioid overdose-related or unrelated causes. In addition, one-way sensitivity and scenario analysis were conducted. RESULTS: Over a 5-year time period, using ADF opioids prevented an additional 2300 new cases of opioid abuse at an additional cost of approximately $535 million to the healthcare sector. Threshold analyses showed that a 40% decrease in ADF opioid costs was required to attain cost neutrality between the 2 cohorts, whereas a 100% effectiveness in abuse reduction still did not result in cost neutrality. A 43% decrease in diversion with ADFs relative to non-ADFs was required to attain cost neutrality. Including a societal perspective produced results directionally similar to the base-case analysis findings. CONCLUSION: ADF opioids have the potential to prevent new cases of opioid abuse, but at substantially higher costs to the health system.


Assuntos
Formulações de Dissuasão de Abuso/economia , Analgésicos Opioides/economia , Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Dor Crônica/economia , Custos de Medicamentos , Transtornos Relacionados ao Uso de Opioides/economia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Uso Indevido de Medicamentos sob Prescrição/economia , Uso Indevido de Medicamentos sob Prescrição/prevenção & controle , Formulações de Dissuasão de Abuso/efeitos adversos , Analgésicos Opioides/efeitos adversos , Dor Crônica/epidemiologia , Análise Custo-Benefício , Composição de Medicamentos , Humanos , Incidência , Modelos Econômicos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
14.
Am J Drug Alcohol Abuse ; 45(4): 377-384, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30990363

RESUMO

Background: Extended-release (ER) morphine formulations are commonly manipulated for non-oral routes of administration, particularly via injection. Morphine ARER, an abuse-deterrent formulation of ER morphine, has both physical and chemical properties that deter abuse. Objectives: To assess the syringeability of morphine ARER using in vitro laboratory studies. Methods: Intact, cut, or crushed morphine ARER tablets were incubated in 1, 5, or 10 mL of room temperature or 90°C water for 1, 5, 10, or 30 min of agitation. Crushed ER morphine tablets were assessed in 10 mL room temperature water. The difficulty to draw the mixture into a syringe was assessed on a scale of 1 (very easy) to 10 (impossible). If the prepared mixture was syringeable, released morphine was measured analytically. Results: Crushed and cut morphine ARER tablets formed a viscous material when subjected to a liquid environment and were rated as "impossible to syringe" in ≤5 mL water and were slightly syringeable in 10 mL water. In contrast, all syringeability tests of crushed ER morphine were rated as "very easy to syringe". After 30 min in room temperature water, crushed ER morphine released 75% morphine whereas intact, cut, and crushed morphine ARER tablets released a maximum of 12%, 12%, and 5% of the total morphine content. Heating extractions resulted in increased morphine release. Conclusion: The difficulty to syringe morphine ARER when manipulated suggests that morphine ARER has abuse-deterrent properties that may deter intravenous abuse.


Assuntos
Formulações de Dissuasão de Abuso , Preparações de Ação Retardada/química , Morfina/química , Seringas , Viscosidade , Administração Intravenosa/instrumentação , Comprimidos
15.
Neuropharmacology ; 158: 107619, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31029588

RESUMO

Pain remains a global health challenge. For decades, clinicians have been primarily relying on µ-opioid receptor (MOR) agonists and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management. MOR agonists remain the most efficacious analgesics available; however, adverse effects related to MOR agonists use are severe which often lead to forced drug discontinuation and inadequate pain relief. The recent opioid overdose epidemic urges the development of safer analgesics. Combination therapy is a well-established clinical pharmacotherapeutic strategy for the treatment of various clinical disorders. The combination of MOR agonists with non-MOR agonists may increase the analgesic potency of MOR agonists, reduce the development of tolerance and dependence, reduce the diversion and abuse, overdose, and reduce other clinically significant side effects associated with prolonged opioid use such as constipation. Overall, the combination therapy approach could substantially improve the therapeutic profile of MOR agonists. This review summarizes some recent developments in this field. This article is part of the Special Issue entitled 'New Vistas in Opioid Pharmacology'.


Assuntos
Analgésicos não Entorpecentes/uso terapêutico , Analgésicos Opioides/uso terapêutico , Manejo da Dor/métodos , Formulações de Dissuasão de Abuso , Combinação de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Tolerância a Medicamentos , Humanos , Receptores de Imidazolinas/agonistas , Morfinanos , Antagonistas de Entorpecentes , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Polietilenoglicóis , Desvio de Medicamentos sob Prescrição , Receptores Opioides mu/agonistas
16.
Drug Alcohol Depend ; 198: 13-20, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30861390

RESUMO

INTRODUCTION: Behavioral economics provides a framework for quantifying drug abuse potential that can inform public health risk, clinical treatment, and research. Hypothetical purchase task (HPT) questionnaires may provide a low-cost and sensitive method by which to measure and predict the appeal of pharmaceutical drugs that differ by formulation. However, the validity of this type of analysis must be empirically established by comparing the "essential value" (EV) of different drugs across subgroups. PROCEDURES: This pilot study used HPT assessments and the Exponential Model of Demand to quantify the EV of opioid medications-specifically, easily tampered formulations versus (vs.) abuse-deterrent formulations-in patients with a history of opioid abuse. MAIN FINDINGS: Participants had more inelastic demand for opioid pills than for cigarettes and alcohol. Participants with experience manipulating pills (M group) had more inelastic demand for standard pills vs. participants with no manipulation experience (NM group), and the M group had a more elastic demand for the abuse-deterrent opioid pill than for the standard pill. There was no effect of formulation in the NM group and there was no difference in demand elasticity for abuse-deterrent pills between the two groups. There was a positive correlation between the EVs of different drugs, and between some behavioral economic indices and treatment variables. CONCLUSIONS: Our results suggest that HPTs may provide a sensitive measure of abuse potential that can distinguish between different formulations in at-risk populations.


Assuntos
Formulações de Dissuasão de Abuso/economia , Formulações de Dissuasão de Abuso/psicologia , Analgésicos Opioides/economia , Transtornos Relacionados ao Uso de Opioides/psicologia , Adulto , Economia Comportamental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco , Inquéritos e Questionários
17.
Annu Rev Biomed Eng ; 21: 61-84, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-30786212

RESUMO

Prescription opioid medications have seen a dramatic rise in misuse and abuse, leading regulators and scientists to develop policies and abuse-deterrent technologies to combat the current opioid epidemic. These abuse-deterrent formulations (ADFs) are intended to deter physical and chemical tampering of opioid-based products, while still providing safe and effective delivery for therapeutic purposes. Even though formulations with varying abuse-deterrent technologies have been approved, questions remain about their effectiveness. While these formulations provide a single means to combat the epidemic, a greater emphasis should be placed on formulations for treatment of addiction and overdose to help those struggling with opioid dependence. This article analyzes various ADFs currently in clinical use and explores potential novel systems for treatment of addiction and prevention of overdose.


Assuntos
Analgésicos Opioides/efeitos adversos , Sistemas de Liberação de Medicamentos , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/terapia , Manejo da Dor/tendências , Dor/tratamento farmacológico , Uso Indevido de Medicamentos sob Prescrição/prevenção & controle , Formulações de Dissuasão de Abuso , Aprovação de Equipamentos , Formas de Dosagem , Aprovação de Drogas , Composição de Medicamentos , Rotulagem de Medicamentos , Humanos , Naltrexona/administração & dosagem , Manejo da Dor/métodos , Medicamentos sob Prescrição , Estados Unidos , United States Food and Drug Administration
20.
Pain Pract ; 19(4): 443-454, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30597739

RESUMO

Providers who treat patients with chronic pain face a dual challenge: providing adequate access to opioid therapies for appropriate pain management while adopting strategies to minimize the risk for abuse. Commonly prescribed opioids have substantial abuse potential when administered intravenously, and extended-release (ER)/long-acting (LA) opioids may be targeted for IV abuse because of the higher per-dose medication level. The consequences of IV opioid abuse are severe and increase the risks for adverse outcomes, including mortality due to acute health events, serious infections, and deep vein thrombosis, to name a few. To reduce the potential for abuse of prescription opioids by both recreational and experienced drug abusers, abuse-deterrent formulations (ADFs) of opioid medications employ either physical/chemical barriers or agonist-antagonist combinations. Here we review the development and use of opioid ADFs as a harm-reduction strategy, and their potential for mitigating IV opioid abuse. The approved ER/LA opioids with ADF labeling in the United States include formulations of oxycodone, hydrocodone, and morphine. Findings from in vitro laboratory tests of abuse deterrence for opioid ADFs are described herein, as are data from human abuse potential studies for IV abuse of those ADF products, for which such studies are feasible (ie, abuse-deterrent agonist-antagonist formulations). The available ADF opioids may decrease both the attractiveness and the feasibility of IV abuse. The adoption of ADF opioids represents one tactic for providing access to needed medication for patients with chronic pain, while potentially reducing the risk for opioid abuse, in a comprehensive effort to combat the opioid epidemic.


Assuntos
Formulações de Dissuasão de Abuso/métodos , Analgésicos Opioides/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Manejo da Dor/métodos , Dor Crônica/tratamento farmacológico , Preparações de Ação Retardada/administração & dosagem , Composição de Medicamentos , Humanos , Manejo da Dor/efeitos adversos , Estados Unidos
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