Emerging trends in Abuse-Deterrent Formulations: Technological insights and Regulatory considerations

2021 ◽  
Vol 18 ◽  
Author(s):  
Dhwani Rana ◽  
Sagar Salave ◽  
Derajram Benival
Keyword(s):  
Drug Abuse ◽  
Severe Pain ◽  
Public Health Problem ◽  
Opioid Overdose ◽  
Opioid Epidemic ◽  
Fda Guidance ◽  
Post Marketing ◽  
Chronic Severe Pain ◽  
Alternative Routes

Background: Opioid medications are an integral part in the management of acute and chronic severe pain. However, non-medical practice of these prescription drug products is emerging as a serious public health problem. To control this opioid epidemic, USFDA is encouraging pharmaceutical companies to develop Abuse Deterrent Formulations (ADFs). Abuse Deterrent Formulations are much more difficult to manipulate and abuse when compared to their conventional formulations. This feature of ADFs is due to their ability to incumber extraction of active ingredients, to prevent administration through alternative routes and making abuse of altered product less rewarding. Objective: The main objective of this review is to abridge different ADFs and various laboratory-based in vitro manipulation and extraction studies, demonstrating that these approved ADFs have capabilities to deter abuse. Methods: The method includes collection of data from different search engines like PubMed, FDA guidance documents, ScienceDirect, Google Patents to get coverage of literature in order to get appropriate information regarding ADFs. Results: Various in vitro studies demonstrate that ADFs are effective in minimizing opioid drug abuse including opioid overdose. However, real impact of these ADFs on reducing the drug abuse can be concluded only after receiving the post marketing data. Conclusion: ADFs are embracing fundamentally different paradigm in management of severe pain. We believe that development of abuse deterrent technologies would shift the architype, deterring multipill abuse and can prove as a breakthrough strategy in controlling this opioid epidemic menace.

scholarly journals Current Impact and Application of AbuseDeterrent Opioid Formulations in Clinical Practice

2017 ◽  
Vol 7 (20;7) ◽  
pp. E1003-E1023
Author(s):  
Hsiang-Yin Chen
Keyword(s):  
Clinical Practice ◽  
New Products ◽  
Opioid Abuse ◽  
Mitigation Strategies ◽  
Time Data ◽  
Routes Of Administration ◽  
Fda Guidance ◽  
Advantages And Disadvantages ◽  
Post Marketing ◽  
Alternative Routes

Background: Abuse-deterrent formulations (ADFs) represent one novel strategy for curbing the potential of opioid abuse. Objective: We aim to compare and contrast the characteristics and applications of current abusedeterrent opioid products in clinical practice. Methods: Literature searches were conducted in databases (Pubmed Medline, International Pharmaceutical Abstracts, Google Scholar) and official reports. Relevant data were screened and organized into: 1) epidemiology of opioid abuse, 2) mitigation strategies for reducing opioid abuse, 3) development of ADFs, and 4) clinical experience with these formulations. Results: Increasing trends of opioid abuse and misuse have been reported globally. There are 5 types of abuse-deterrent opioid products: physical chemical barrier, combined agonist/antagonist, sequestered aversive agent, prodrug, and novel delivery system. The advantages and disadvantages of the 5 options are discussed in this review. A total of 9 products with abuse-deterrent labels have been approved by the Food and Drug Administration (FDA). The rates of abuse, diversion, and overdose deaths of these new products are also discussed. A framework for collecting in-time data on the efficacy, benefit and risk ratio, and cost-effectiveness of these new products is suggested to facilitate their optimal use. Limitations: The present review did not utilize systematic review standards or meta-analytic techniques, given the large heterogeneity of data and outcomes reviewed. Conclusions: ADFs provide an option for inhibiting the abuse or misuse of oral opioid products by hindering extraction of the active ingredient, preventing alternative routes of administration, or causing aversion. Their relatively high costs, uncertain insurance policies, and limited data on pharmacoeconomics warrant collaborative monitoring and assessment by government agencies, pharmaceutical manufacturers, and data analysis services to define their therapeutic role in the future. Key words: Opioid abuse, abuse-deterrent formulations, ADF, post-marketing, FDA guidance, cost impact, abuse liking, physician attitude, generic abuse-deterrent formulation, clinical application

Medicinal Plants and Bioactive Compounds for Diabetes Management: Important Advances for Drug Discovery

2020 ◽  
Vol 26 ◽  
Author(s):  
Kondeti Ramudu Shanmugam ◽  
Bhasha Shanmugam ◽  
Gangigunta Venkatasubbaiah ◽  
Sahukari Ravi ◽  
Kesireddy Sathyavelu Reddy
Keyword(s):  
Herbal Medicine ◽  
Medicinal Plants ◽  
Bioactive Compounds ◽  
Diabetes Management ◽  
Therapeutic Potential ◽  
Public Health Problem ◽  
In Vivo Studies ◽  
Major Public Health Problem

Background : Diabetes is a major public health problem in the world. It affects each and every part of the human body and also leads to organ failure. Hence, great progress made in the field of herbal medicine and diabetic research. Objectives: Our review will focus on the effect of bioactive compounds of medicinal plants which are used to treat diabetes in India and other countries. Methods: Information regarding diabetes, oxidative stress, medicinal plants and bioactive compounds were collected from different search engines like Science direct, Springer, Wiley online library, Taylor and francis, Bentham Science, Pubmed and Google scholar. Data was analyzed and summarized in the review. Results and Conclusion: Anti-diabetic drugs that are in use have many side effects on vital organs like heart, liver, kidney and brain. There is an urgent need for alternative medicine to treat diabetes and their disorders. In India and other countries herbal medicine was used to treat diabetes. Many herbal plants have antidiabetic effects. The plants like ginger, phyllanthus, curcumin, aswagandha, aloe, hibiscus and curcuma showed significant anti-hyperglycemic activities in experimental models and humans. The bioactive compounds like Allicin, azadirachtin, cajanin, curcumin, querceitin, gingerol possesses anti-diabetic, antioxidant and other pharmacological properties. This review focuses on the role of bioactive compounds of medicinal plants in prevention and management of diabetes. Conclusion: Moreover, our review suggests that bioactive compounds have the potential therapeutic potential against diabetes. However, further in vitro and in vivo studies are needed to validate these findings.

Synthesis and Antifungal Activity of Coumarins Derivatives Against Sporothrix spp.

2018 ◽  
Vol 18 (2) ◽  
pp. 164-171 ◽  
Author(s):  
Luana da S.M. Forezi ◽  
Luana Pereira Borba-Santos ◽  
Mariana F.C. Cardoso ◽  
Vitor F. Ferreira ◽  
Sonia Rozental ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agents ◽  
Sporothrix Schenckii ◽  
Public Health Problem ◽  
Domestic Animals ◽  
Coumarin Derivatives ◽  
Sporothrix Brasiliensis ◽  
Synthetic Routes ◽  
Effective Drugs

Sporotrichosis is a serious public health problem in Brazil that affects human patients and domestic animals, mainly cats. Thus, the search for new antifungal agents is required also due to the emergence and to the lack of effective drugs available in the therapeutic arsenal. The aim of this study was to evaluate the in vitro antifungal profile of two synthetic series of coumarin derivatives against Sporothrix schenckii and Sporothrix brasiliensis. The three-components synthetic routes used for the preparation of coumarin derivatives have proved to be quite efficient and compounds 16 and 17 have been prepared in good yields. The inhibitory activity of nineteen synthetic coumarins derivatives 16a-i and 17a-j were evaluated against Sporothrix spp. yeasts and the most potent compounds were 16b and 17i. However, according to concentrations able to inhibit (minimum inhibitory concentrations) and kill (minimum fungicidal concentrations) the cells, 17i was more effective than 16b against Sporothrix spp. Thus, 17i exhibited good antifungal activity against S. brasiliensis and S. schenckii, suggesting that it is an important scaffold for the development of novel antifungal agents.

Nanoparticles and Its Implications in HIV/AIDS Therapy

2020 ◽  
Vol 17 (4) ◽  
pp. 448-456 ◽  
Author(s):  
Victor B. Oti
Keyword(s):  
Direct Injection ◽  
Oral Intake ◽  
Public Health Problem ◽  
Antiretroviral Drugs ◽  
The Body ◽  
Viral Agent ◽  
Treatment And Prevention ◽  
Prevention And Treatment ◽  
Hiv Aids

The use of Antiretroviral drugs in treating HIV/ AIDS patients has enormously increased their life spans with serious disadvantages. The virus infection still remains a public health problem worldwide with no cure and vaccine for the viral agent until now. The use of nanoparticles (NPs) for the treatment and prevention of HIV/AIDS is an emerging technology of the 21st century. NPs are solid and colloid particles with 10 nm to <1000 nm size range; although, less than 200 nm is the recommended size for nanomedical usage. There are NPs with therapeutic capabilities such as liposomes, micelles, dendrimers and nanocapsules. The particle enters the body mainly via oral intake, direct injection and inhalation. It has been proven to have potentials of advancing the prevention and treatment of the viral agent. Certain NPs have been shown to have selftherapeutic activity for the virus in vitro. Strategies that are novel are emerging which can be used to improve nanotechnology, such as genetic treatment and immunotherapy. In this review, nanoparticles, the types and its characteristics in drug delivery were discussed. The light was furthermore shed on its implications in the prevention and treatment of HIV/AIDS.

Commercial Fishing as an Occupational Determinant of Opioid Overdoses and Deaths of Despair in Two Massachusetts Fishing Ports, 2000–2014

2021 ◽  
pp. 104829112110234
Author(s):  
Scott Fulmer ◽  
Shruti Jain ◽  
David Kriebel
Keyword(s):  
United States ◽  
Cause Of Death ◽  
Death Certificate ◽  
The United States ◽  
Opioid Overdose ◽  
Commercial Fishing ◽  
Opioid Epidemic ◽  
Death Certificate Data ◽  
Deaths Of Despair

The opioid epidemic has had disproportionate effects across various sectors of the population, differentially impacting various occupations. Commercial fishing has among the highest rates of occupational fatalities in the United States. This study used death certificate data from two Massachusetts fishing ports to calculate proportionate mortality ratios of fatal opioid overdose as a cause of death in commercial fishing. Statistically significant proportionate mortality ratios revealed that commercial fishermen were greater than four times more likely to die from opioid poisoning than nonfishermen living in the same fishing ports. These important quantitative findings suggest opioid overdoses, and deaths to diseases of despair in general, deserve further study in prevention, particularly among those employed in commercial fishing.

scholarly journals Microwave-Assisted Synthesis of (Piperidin-1-yl)quinolin-3-yl)methylene)hydrazinecarbothioamides as Potent Inhibitors of Cholinesterases: A Biochemical and In Silico Approach

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 656
Author(s):  
Rubina Munir ◽  
Muhammad Zia-ur-Rehman ◽  
Shahzad Murtaza ◽  
Sumera Zaib ◽  
Noman Javid ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Critical Role ◽  
Public Health Problem ◽  
Microwave Assisted Synthesis ◽  
Major Public Health Problem ◽  
Spectroscopic Techniques ◽  
Dual Inhibitor ◽  
Microwave Assisted ◽  
Ic50 Values

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, characterized by central cognitive dysfunction, memory loss, and intellectual decline poses a major public health problem affecting millions of people around the globe. Despite several clinically approved drugs and development of anti-Alzheimer’s heterocyclic structural leads, the treatment of AD requires safer hybrid therapeutics with characteristic structural and biochemical properties. In this endeavor, we herein report a microwave-assisted synthesis of a library of quinoline thiosemicarbazones endowed with a piperidine moiety, achieved via the condensation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes and (un)substituted thiosemicarbazides. The target N-heterocyclic products were isolated in excellent yields. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). Anti-Alzheimer potential of the synthesized heterocyclic compounds was evaluated using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vitro biochemical assay results revealed several compounds as potent inhibitors of both enzymes. Among them, five compounds exhibited IC50 values less than 20 μM. N-(3-chlorophenyl)-2-((8-methyl-2-(piperidin-1-yl)quinolin-3-yl)methylene)hydrazine carbothioamide emerged as the most potent dual inhibitor of AChE and BChE with IC50 values of 9.68 and 11.59 μM, respectively. Various informative structure–activity relationship (SAR) analyses were also concluded indicating the critical role of substitution pattern on the inhibitory efficacy of the tested derivatives. In vitro results were further validated through molecular docking analysis where interactive behavior of the potent inhibitors within the active pocket of enzymes was established. Quinoline thiosemicarbazones were also tested for their cytotoxicity using MTT assay against HepG2 cells. Among the 26 novel compounds, there were five cytotoxical and 18 showed proliferative properties.

scholarly journals In Vitro and In Silico Anti-Arboviral Activities of Dihalogenated Phenolic Derivates of L-Tyrosine

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3430
Author(s):  
Vanessa Loaiza-Cano ◽  
Laura Milena Monsalve-Escudero ◽  
Manuel Pastrana Restrepo ◽  
Diana Carolina Quintero-Gil ◽  
Sergio Andres Pulido Muñoz ◽  
...  
Keyword(s):  
Cell Line ◽  
Viral Protein ◽  
In Silico ◽  
Public Health Problem ◽  
Cellular Proteins ◽  
Vero Cell Line ◽  
Viral Particles ◽  
Pre Treatment ◽  
Line Infection

Despite the serious public health problem represented by the diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses, there are still no specific licensed antivirals available for their treatment. Here, we examined the potential anti-arbovirus activity of ten di-halogenated compounds derived from L-tyrosine with modifications in amine and carboxyl groups. The activity of compounds on VERO cell line infection and the possible mechanism of action of the most promising compounds were evaluated. Finally, molecular docking between the compounds and viral and cellular proteins was evaluated in silico with Autodock Vina®, and the molecular dynamic with Gromacs®. Only two compounds (TDC-2M-ME and TDB-2M-ME) inhibited both ZIKV and CHIKV. Within the possible mechanism, in CHIKV, the two compounds decreased the number of genome copies and in the pre-treatment strategy the infectious viral particles. In the ZIKV model, only TDB-2M-ME inhibited the viral protein and demonstrate a virucidal effect. Moreover, in the U937 cell line infected with CHIKV, both compounds inhibited the viral protein and TDB-2M-ME inhibited the viral genome too. Finally, the in silico results showed a favorable binding energy between the compounds and the helicases of both viral models, the NSP3 of CHIKV and cellular proteins DDC and β2 adrenoreceptor.

scholarly journals The gut at war: the consequences of enteropathogenic Escherichia coli infection as a factor of diarrhea and malnutrition

2000 ◽  
Vol 118 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Ulysses Fagundes-Neto ◽  
Isabel Cristina Affonso Scaletsky
Keyword(s):  
Escherichia Coli ◽  
Diarrheal Disease ◽  
Driving Forces ◽  
Public Health Problem ◽  
Clinical Aspects ◽  
Small Intestinal Mucosa ◽  
Enteropathogenic Escherichia Coli ◽  
Important Public Health Problem ◽  
The Impact

Diarrheal disease is still the most prevalent and important public health problem in developing countries, despite advances in knowledge, understanding, and management that have occurred over recent years. Diarrhea is the leading cause of death in children under 5 years of age. The impact of diarrheal diseases is more severe in the earliest periods of life, when taking into account both the numbers of episodes per year and hospital admission rates. This narrative review focuses on one of the major driving forces that attack the host, namely the enteropathogenic Escherichia coli (EPEC) and the consequences that generate malnutrition in an early phase of life. EPEC serotypes form dense microcolonies on the surface of tissue-culture cells in a pattern known as localized adherence (LA). When EPEC strains adhere to epithelial cells in vitro or in vivo they cause characteristic changes known as Attaching and Effacement (A/E) lesions. Surface abnormalities of the small intestinal mucosa shown by scanning electron microscopy in infants with persistent diarrhea, although non-specific, are intense enough to justify the severity of the clinical aspects displayed in a very young phase in life. Decrease in number and height of microvilli, blunting of borders of enterocytes, loss of the glycocalyx, shortening of villi and presence of a mucus pseudomembrane coating the mucosal surface were the abnormalities observed in the majority of patients. These ultrastructural derangements may be due to an association of the enteric enteropathogenic agent that triggers the diarrheic process and the onset of food intolerance responsible for perpetuation of diarrhea. An aggressive therapeutic approach based on appropriate nutritional support, especially the utilization of human milk and/or lactose-free protein hydrolyzate-based formulas and the adequate correction of the fecal losses, is required to allow complete recovery from the damage caused by this devastating enteropathogenic agent.

Antioxidant, Antiprotoscolices Activity of Ethanolic Extracts of Some Medicinal Plants Against Echinococcus granulosus as Eco-friendly System

2021 ◽  
Vol 18 (4) ◽  
pp. 87-94
Author(s):  
Amer Abed ◽  
Orooba Ibrahim
Keyword(s):  
Medicinal Plants ◽  
Echinococcus Granulosus ◽  
Parasitic Infection ◽  
Public Health Problem ◽  
Good Alternative ◽  
Thymus Vulgaris ◽  
Mentha Spicata ◽  
Time Dependent Effect ◽  
Promising Source

The principal objective of the study is to investigate the use of Mentha spicata, Thymus vulgaris and Ocimum basilicum as a good alternative option to Antiprotoscolices in-vitro. Hydatid disease, a zoonotic parasitic infection caused by Echinococcus granulosus, an important economic and human public health problem with a wide geographical distribution. Fertile hydatid cysts were collected from livestock and the viability of the protoscolices was confirmed. Protoscolices were subjected to four different concentrations of organic extracts (12.5, 25, 50 and 75 mg/ml) for 10, 20 and 30 min. Each extract was investigated and viability of the protoscolices was tested using 0.1% eosin staining. The highest efficacy was by T. vulgaris, M. spicata (100%), and O. basilicum (98.8%) respectively, after exposure of 20 minutes at 75 mg/ml, that lead to the significant reduction in the viability of protoscolices. The extract had time-dependent effect. Phytochemical were identified qualitatively and weighted quantitatively, that help in the identification of bioactive compounds involved in selective action on the protoscolices tegument layer. In conclusion, all the selected medicinal plants could be a promising source of potent antiprotoscolices effect. The mechanism by which plant extracts killed protoscolices and also their safety for living cells are unclear and need to be investigated further.

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