Abuse-deterrent properties of REMOXY® ER, a high-viscosity extended-release oxycodone formulation

2018 ◽  
Vol 14 (6) ◽  
pp. 429-436 ◽  
Author(s):  
Shawn A. Kucera, PhD ◽  
Michael S. Zamloot, BS ChE ◽  
Michael M. Crowley, PhD ◽  
Lindsay H. Burns, PhD ◽  
Nadav Friedmann, PhD, MD ◽  
...  
Keyword(s):  
Extended Release ◽  
First Generation ◽  
Chemical Properties ◽  
High Viscosity ◽  
Opioid Abuse ◽  
Abuse Potential ◽  
In Vitro Studies ◽  
Opioid Epidemic ◽  
Physical Chemical

Objective: These in vitro studies compared abuse-deterrent properties of REMOXY ER (extended-release oxycodone), a novel, high-viscosity gel formulation, versus the two currently marketed ER oxycodone formulations.Methods: Tampering methods were tailored to each product to maximize oxycodone release with the least complexity, time, and effort, based on the physical/chemical properties of each formulation. Oral abuse was simulated by extracting oxycodone from each manipulated formulation in Common Ingestible Liquids and in Advanced Solvents (not ingestible and requiring additional separation). To simulate injection abuse, oxycodone was extracted from each manipulated formulation in low volumes of injection vehicles, heated or unheated. Inhalation abuse potential was assessed by volatilization.Results: In oral abuse simulations, manipulated REMOXY ER released 2-22 percent of its oxycodone in 20 minutes in five Common Ingestible Liquids, versus 77-85 percent oxycodone released from OxyContin® ER in 5 minutes in four of the five. In six Advanced Solvents, REMOXY ER released 3-37 percent at 20 minutes, versus 55-89 percent released from OxyContin ER at 5 minutes. Minimal oxycodone was extracted from REMOXY ER in five injection vehicles, heated or unheated. In contrast, OxyContin ER released 65-87 percent of its oxycodone within 10 minutes in all vehicles, regardless of heating. Xtampza® ER released 96 percent of its oxycodone in a heated injection vehicle and released 50-60 percent in two unheated injection vehicles. Showing minimal inhalation abuse potential, 9 percent of oxycodone was vaporized from manipulated REMOXY ER at 20 minutes compared to 8.8 percent at 5 minutes for OxyContin ER.Conclusions: In these studies, REMOXY ER demonstrated robust and meaningful abuse-deterrence relative to OxyContin ER and Xtampza ER.Perspective: Abuse-deterrent drugs were intended to help fight opioid abuse. Yet, the persistence of the opioid epidemic indicates that vast improvements in abuse-deterrent technology are sorely needed. A new, high-viscosity, ER oxycodone formulation showed much improved abuse-deterrent properties in simulations of oral, injection, and inhalation abuse, compared to earlier, first-generation formulations.

scholarly journals Insights in Behavior of Variably Formulated Alginate-Based Microcapsules for Cell Transplantation

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Pia Montanucci ◽  
Silvia Terenzi ◽  
Claudio Santi ◽  
Ilaria Pennoni ◽  
Vittorio Bini ◽  
...  
Keyword(s):  
Divalent Cations ◽  
Chemical Properties ◽  
Live Cells ◽  
High Performing ◽  
Physical Chemical ◽  
Degenerative Disorders ◽  
Selection Of ◽  
Better Than

Alginate-based microencapsulation of live cells may offer the opportunity to treat chronic and degenerative disorders. So far, a thorough assessment of physical-chemical behavior of alginate-based microbeads remains cloudy. A disputed issue is which divalent cation to choose for a high performing alginate gelling process. Having selected, in our system, high mannuronic (M) enriched alginates, we studied different gelling cations and their combinations to determine their eventual influence on physical-chemical properties of the final microcapsules preparation,in vitroandin vivo. We have shown that used of ultrapure alginate allows for high biocompatibility of the formed microcapsules, regardless of gelation agents, while use of different gelling cations is associated with corresponding variable effects on the capsules’ basic architecture, as originally reported in this work. However, only the final application which the capsules are destined to will ultimately guide the selection of the ideal, specific gelling divalent cations, since in principle there are no capsules that are better than others.

Physical-chemical properties and in vitro digestibility of phosphorylated and glycosylated soy protein isolate

LWT ◽  
2021 ◽  
Vol 152 ◽  
pp. 112380
Author(s):  
Jingyuan Liu ◽  
Yangling Wan ◽  
Liuyang Ren ◽  
Mengdi Li ◽  
Ying Lv ◽  
...  
Keyword(s):  
Soy Protein ◽  
Soy Protein Isolate ◽  
Chemical Properties ◽  
Protein Isolate ◽  
In Vitro Digestibility ◽  
Physical Chemical

P–250 Mineral oil with high viscosity improves the stability of pH and osmolality in the human in vitro culture system

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Mestres ◽  
Q Matia-Algué ◽  
A Villamar ◽  
M García-Jiménez ◽  
A Casals ◽  
...  
Keyword(s):  
Embryo Culture ◽  
Culture System ◽  
Chemical Properties ◽  
High Viscosity ◽  
Mineral Oil ◽  
Culture Conditions ◽  
Physico Chemical ◽  
Temperature Loss ◽  
The Stability

Abstract Study question Do commercial mineral oil brands differ in their capacity to stabilize the human embryo culture system, and is this related to the oil’s viscosity? Summary answer While the oils’ viscosity only had minor effects on temperature maintenance, it showed a direct correlation with the stability of pH and osmolality during culture. What is known already Mineral oil is a key component of the in vitro embryo culture system, which stabilizes temperature, pH and osmolality of the media during culture. Its use has been implemented worldwide for several decades and many manufacturers currently produce and commercialize oil intended for human embryo culture. Unfortunately, oil remains as one of the less characterized products in the IVF laboratory due to a lack of standardized nomenclature, production and testing. With differing physico-chemical properties, such as viscosity, oils produced by various manufacturers could behave differently to the same culture conditions and, thus, its use may need to be adjusted accordingly. Study design, size, duration Viscosity was quantified in three high-viscosity (H-V) and three low-viscosity (L-V) oils with a viscosity-meter. The required time for media’s pH to equilibrate using each oil was studied, as well as its subsequent stability outside the incubator for 30min. In-drop temperature was assessed during 15min when taking a dish outside the incubator, and again when putting it back. Additionally, each oil’s capacity to avoid media evaporation was studied with daily osmolality measurements during 7 days. Participants/materials, setting, methods pH equilibration was measured with a continuous pHmeter (Log&Guard, Vitrolife) in 4-well dishes prepared with 600µl of medium and 500µl of oil. For the other experiments, 35mm dishes with 4ml of oil and 20µl media droplets were used. pH stability was assessed after 0, 15 and 30min outside the incubator with a blood-gas-analyzer (epoc,SiemensHelthineers). A fine-gauge thermocouple was used to measure in-drop temperature loss/recovery. Daily osmolality readings were taken with a vapor pressure osmometer (Vapro5600,Wescor). Main results and the role of chance The selected oil samples had a viscosity of 115, 111, 52, 22, 18, and 12cP. The medium’s pH took approximately 12h to completely equilibrate under H-V oils, while it took less than 4h in L-V. Similarly, the rise in pH after 30min on a heated stage outside of the incubator with room atmosphere was 0.03, 0.04, 0.06, 0.13, 0.17, and 0.26, respectively. Dishes were taken out of the incubator and placed on a heated surface. In the first five minutes, the in-drop temperature loss ranged between –0.22 and –0.13oC/min, with no significant differences observed between oil types. However, temperature plateaued at a significantly higher value in L-V oils (36.5oC), compared to H-V brands (36.25–36.1oC; p = 0.0005). By contrast, all samples followed a similar pattern when the dishes were returned to the benchtop incubator, with temperature taking around 7 minutes to completely recover. Some media evaporated in all oil groups during the 7-day culture in a dry benchtop incubator. The linear regression performed to compare the evaporation rate between groups showed a statistically significant correlation between oil viscosity and the rate of evaporation (p < 0.0001), with an osmolality rise ranging between +2.55mmol/kg/day in the most viscous oil and +6.29mmol/kg/day in the least viscous. Limitations, reasons for caution While the selected oils for this study represent a wide range of options in the market, future projects could widen this selection and include additional tests, such as optimized bioassays. Results may vary between centers, and thus each laboratory should test and optimize their culture system with their own settings. Wider implications of the findings: Different oil brands have shown differing physico-chemical properties that have a direct effect on the culture system and the stability of several culture conditions. These results may be of major importance to adapt the settings and methodologies followed in each IVF laboratory according to the type of oil being used. Trial registration number Not applicable

scholarly journals Screening a library of 1600 adamantyl ureas for anti-Mycobacterium tuberculosis activity in vitro and for better physical chemical properties for bioavailability

2012 ◽  
Vol 20 (10) ◽  
pp. 3255-3262 ◽  
Author(s):  
Michael S. Scherman ◽  
Elton J. North ◽  
Victoria Jones ◽  
Tamara N. Hess ◽  
Anna E. Grzegorzewicz ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Chemical Properties ◽  
Physical Chemical ◽  
Tuberculosis Activity

Comparative evaluation of the biocompatible and physical–chemical properties of poly(lactide-co-glycolide) and polydopamine as coating materials for bacterial cellulose

2019 ◽  
Vol 7 (4) ◽  
pp. 630-639 ◽  
Author(s):  
Lai C. ◽  
S. J. Zhang ◽  
L. Y. Sheng ◽  
T. F. Xi
Keyword(s):  
Bacterial Cellulose ◽  
Comparative Evaluation ◽  
Chemical Properties ◽  
Tissue Reaction ◽  
Cell Behavior ◽  
Coating Materials ◽  
Physical Chemical ◽  
Surface Performance

The aim of this study was to investigate the influence of poly(lactide-co-glycolide) (PLGA) and polydopamine (PDA) as coating materials on the tensile strength, surface performance, in vitro cell behavior and the in vivo material-tissue reaction of bacterial cellulose (BC) membranes.

Fabrication of Extended Release Tablets of Pramipexole: In-vitro Studies

2017 ◽  
Vol 8 (2) ◽  
pp. 115-120 ◽  
Author(s):  
Kambham Venkateswarlu ◽  
Heerasingh Thakur ◽  
Thumati Nagendra Bhaskar Babu
Keyword(s):  
Extended Release ◽  
In Vitro Studies

About Mechanisms of Biological Activity of the Nano- and Microparticles of Natural Minerals in the Experiment

10.12737/2753 ◽  
2013 ◽  
Vol 20 (4) ◽  
pp. 160-165
Author(s):  
Сергиевич ◽  
A. Sergievich ◽  
Чайка ◽  
Vladimir Chayka ◽  
Голохваст ◽  
...  
Keyword(s):  
Biological Activity ◽  
Biological Effects ◽  
Chemical Properties ◽  
Functional Condition ◽  
World Science ◽  
Natural Minerals ◽  
Physical Chemical ◽  
Physical And Chemical

There are both in the domestic and the world science a discussion about the biological activity of water-insoluble solid microparticles technogenous and natural. These interactions are studied in the context of the professional pathology, hygiene and nanotoxicology. The purpose of this research was to study the mechanisms of action of particles of natural minerals of various sizes on biological systems. The paper is based on the applied modern methods which allow to determine the degree of interaction of microelements with the functional systems of the organism. Analysis of the results showed that the application of these methods has a number of shortcomings in the experiments in vivo and in vitro, associated with the physical and chemical features of zeolites. It is established that under cultivation in 6- and 24-hole tablets, the zeolite in a dose of 50 mg/ml covers all the cells attached to the glass. In the fields of view of the cells are practically invisible. Thus, an assessment of toxic effects or functional condition of the cells is not possible. Zeolite being water-insoluble compound wich is not subjected to the pipetting. At the delete zeolite of culture, there is practically full elimination of cells from the hole. Accumulation of the primary information about the biological effects of nano - and microparticles is extremely important. This allows the authors to make some conclusions, but the decision of a question on the mechanism of biological activity, especially the prediction of some properties of particles without the study of physical-chemical properties of the particles isn´t possible.

Influence of lecithin on some physical chemical properties of poloxamer gels: rheological, microscopic and in vitro permeation studies

1999 ◽  
Vol 193 (1) ◽  
pp. 49-55 ◽  
Author(s):  
M.Vitória L.B Bentley ◽  
Juliana M Marchetti ◽  
Nágila Ricardo ◽  
Ziad Ali-Abi ◽  
John H Collett
Keyword(s):  
Chemical Properties ◽  
Physical Chemical ◽  
In Vitro Permeation ◽  
Permeation Studies

scholarly journals MON-LB60 Prolactin Response to Metformin in Cabergoline-Resistant Prolactinomas: A Prospective Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Luiz Henrique Corrêa Portari ◽  
Silvia Regina Correa-Silva ◽  
Julio Abucham
Keyword(s):  
Extended Release ◽  
Prolactin Secretion ◽  
In Vitro Studies ◽  
Metformin Treatment ◽  
Fasting Glycemia ◽  
Prolactin Response ◽  
A Prospective Study

Abstract Introduction: Prolactinomas are the most frequent pituitary-secreting tumors. Medical therapy with cabergoline (CAB), a dopamine agonist (DA), is the first line treatment, but 10% of prolactinomas are resistant to CAB. Recently, in vitro studies have shown anti-tumoral activity of metformin and other biguanids in human prolactinomas1, which prompted us to investigate that possibility in vivo. Aim: To evaluate the effect of metformin (MET) on Prolactin (PRL) secretion in patients with CAB resistant prolactinomas. Design and Setting: Prospective interventional study in a single referral center. Subjects: Ten patients (7 M; mean age: 44 ± 12y) with CAB resistant (PRL: 148 ± 125ng/ml; range: 38 - 386) prolactinomas (all macroadenomas) and metabolic syndrome on maximally tolerated CAB doses (4.3 ± 1.2 mg/week; range: 2.0-7.0) for ≥ 6 months (45 ± 39mo; range: 6-120). Intervention: Oral extended release metformin (p.o.) was prescribed according to patient’s tolerance (mean dose: 1.3 ± 0.4 g; range: 1.0-2.0). Main Outcome Measurements: Serum PRL (Elecsys, Roche, Indianapolis, USA), body weight (BW), fasting glycemia (FG) and HbA1C were evaluated before and at two time points during metformin treatment (30-60 and 120-180 days). Results: BW, FG, and/or HbA1C reductions were observed in 9/10 patients and mean FG decreased significantly (P=0.04). No significant changes were observed in serum PRL levels during metformin treatment [134 ± 124 ng/ml vs 138 ± 132 ng/ml vs 144 ± 129 ng/ml, before, at 30-60 days and at 120-180 days, respectively (P=0.499, mixed-effects analysis with the Geisser-Greenhouse correction)]. Individually, two patients exhibited a ≥ 50% decrease in PRL levels at a single timepoint (one at 30-60 days, with a further increase at 120-180 days and the other at 120-180 days). Conclusion: Metformin, at usual doses, did not inhibit prolactin secretion in patients with cabergoline-resistant prolactinomas. The discrepancy between our results and in vitro studies is not clear, but may be related to the much higher concentrations of metformin used in vitro1 as compared to the serum concentrations observed in patients during metformin treatment2. References: 1Gao J et al. Metformin inhibits growth and prolactin secretion of pituitary prolactinoma cells and xenografts. J Cell Mol Med. 2018 22:6368-79; 2 Frid A et al. Novel assay of metformin levels in patients with type 2 diabetes and varying levels of renal function: clinical recommendations. Diabetes Care 2010 33:1291-3.

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