scholarly journals A Literature Review of the Physicochemical, Physiological and Pharmaceutical Considerations in GIT Absorption of Drugs.

2017 ◽  
Vol II (I) ◽  
pp. 18-33
Author(s):  
Rabia Mazhar ◽  
Fariah Qaise ◽  
Sana Ali Zahra ◽  
Syeda Komal Fatima ◽  
Imran Khan
Keyword(s):  
Drug Development ◽  
Drug Absorption ◽  
Oral Route ◽  
Physiological Factors ◽  
New Drug ◽  
Physico Chemical ◽  
Key Factor ◽  
New Drug Development

Oral route of drug administration is the most common among all routes and hence their pharmacokinetic and pharmacodynamic factors are substantial to study. Among such factors, GIT absorption is the key factor in new drug development affecting the efficacy as well as safety of the drug. Different protocols have now been developed for the usage of in vitro also the in vivo as well as in situ methods in drug absorption determination. In this article, different mechanisms like passive diffusion, pore transport, ionic-mediated transport, endocytosis and other mechanisms involved in drug absorption will be explained. Moreover, different factors i.e. physico-chemical, pharmaceutical and physiological factors that affect drug absorption have been summarized as they play a significant role in the research studies for new drug development. Different absorption determining methods are also discussed.

A physiologically based biopharmaceutical analysis of zolpidem

2021 ◽  
Author(s):  
◽  
Rafael Leal Monteiro Paraiso
Keyword(s):  
Drug Development ◽  
Drug Absorption ◽  
Oral Absorption ◽  
Food Effect ◽  
Simulation Software ◽  
Oral Drug ◽  
Oral Drug Absorption ◽  
Physiologically Based

Computational oral absorption models, in particular PBBM models, provide a powerful tool for researchers and pharmaceutical scientists in drug discovery and formulation development, as they mimic and can describe the physiologically processes relevant to the oral absorption. PBBM models provide in vivo context to in vitro data experiments and allow for a dynamic understanding of in vivo drug disposition that is not typically provided by data from standard in vitro assays. Investigations using these models permit informed decision-making, especially regarding to formulation strategies in drug development. PBBM models, but can also be used to investigate and provide insight into mechanisms responsible for complex phenomena such as food effect in drug absorption. Although there are obviously still some gaps regarding the in silico construction of the gastrointestinal environment, ongoing research in the area of oral drug absorption (e.g. the UNGAP, AGE-POP and InPharma projects) will increase knowledge and enable improvement of these models. PBBM can nowadays provide an alternative approach to the development of in vitro–in vivo correlations. The case studies presented in this thesis demonstrate how PBBM can address a mechanistic understanding of the negative food effect and be used to set clinically relevant dissolution specification for zolpidem immediate release tablets. In both cases, we demonstrated the importance of integrating drug properties with physiological variables to mechanistically understand and observe the impact of these parameters on oral drug absorption. Various complex physiological processes are initiated upon food consumption, which can enhance or reduce a drug’s dissolution, solubility, and permeability and thus lead to changes in drug absorption. With improvements in modeling and simulation software and design of in vitro studies, PBBM modeling of food effects may eventually serve as a surrogate for clinical food effect studies for new doses and formulations or drugs. Furthermore, the application of these models may be even more critical in case of compounds where execution of clinical studies in healthy volunteers would be difficult (e.g., oncology drugs). In the fourth chapter we have demonstrated the establishment of the link between biopredictive in vitro dissolution testing (QC or biorelevant method) PBBM coupled with PD modeling opens the opportunity to set truly clinically relevant specifications for drug release. This approach can be extended to other drugs regardless of its classification according to the BCS. With the increased adoption of PBBM, we expect that best practices in development and verification of these models will be established that can eventually inform a regulatory guidance. Therefore, the application of Physiologically Based Biopharmaceutical Modelling is an area with great potential to streamline late-stage drug development and impact on regulatory approval procedures. Freie Schlagwörter / Tags

scholarly journals Drug Absorption Parameters Obtained Using the Isolated Perfused Rat Lung Model Are Predictive of Rat In Vivo Lung Absorption

2020 ◽  
Vol 22 (3) ◽  
Author(s):  
Johanna Eriksson ◽  
Erik Sjögren ◽  
Hans Lennernäs ◽  
Helena Thörn
Keyword(s):  
Drug Development ◽  
Drug Absorption ◽  
Ex Vivo ◽  
Lung Model ◽  
Pharmacokinetic Data ◽  
Rat Lung ◽  
Time Profiles ◽  
Input Parameters

AbstractThe ex vivo isolated perfused rat lung (IPL) model has been demonstrated to be a useful tool during drug development for studying pulmonary drug absorption. This study aims to investigate the potential use of IPL data to predict rat in vivo lung absorption. Absorption parameters determined from IPL data (ex vivo input parameters) in combination with intravenously determined pharmacokinetic data were used in a biopharmaceutics model to predict experimental rat in vivo plasma concentration-time profiles and lung amount after inhalation of five different inhalation compounds. The performance of simulations using ex vivo input parameters was compared with simulations using in vitro input parameters, to determine whether and to what extent predictability could be improved by using input parameters determined from the more complex ex vivo model. Simulations using ex vivo input parameters were within twofold average difference (AAFE < 2) from experimental in vivo data for all compounds except one. Furthermore, simulations using ex vivo input parameters performed significantly better than simulations using in vitro input parameters in predicting in vivo lung absorption. It could therefore be advantageous to base predictions of drug performance on IPL data rather than on in vitro data during drug development to increase mechanistic understanding of pulmonary drug absorption and to better understand how different substance properties and formulations might affect in vivo behavior of inhalation compounds.

scholarly journals Amygdalin as a Plant-Based Bioactive Constituent: A Mini-Review on Intervention with Gut Microbiota, Anticancer Mechanisms, Bioavailability, and Microencapsulation

Proceedings ◽  
2020 ◽  
Vol 61 (1) ◽  
pp. 15
Author(s):  
Hassan Barakat
Keyword(s):  
Gut Microbiota ◽  
Oral Route ◽  
Oral Dosage ◽  
Intravenous Route ◽  
Key Factor ◽  
Bitter Almond ◽  
Cancerous Cells ◽  
Bioactive Constituent

Amygdalin—a plant-based bioactive constituent particularly abundant in bitter almond has been identified as featuring the cyanogenic glycoside chemical organic compound which was originally intended to be a medication for cancer treatment once hydrolyzed to hydrogen cyanide (HCN). Unfortunately, studies have revealed that HCN can similarly affect normal cells, rendering it harming the human body. Both in vivo and in vitro investigations are extremely controversial and make its use unsafe. An updated substantial review on the source, structure, intervention with gut microbiota, anticancer therapy, bioavailability, and microencapsulation of amygdalin was summarized. Amygdalin provided anti-tumor, anti-fibrotic, anti-atherosclerosis, anti-inflammatory, immunomodulatory, analgesic, ameliorating digestive and reproductive systems, and enhancing neurodegeneration as well as myocardial hypertrophy. Studies confirmed the toxicity of amygdalin produced by its HCN after oral ingestion. However, the intravenous route of administration was much less toxic than the oral route and can be avoided with an oral dosage ranging from 0.6 to 1 g daily. The diversity of gut consortium is a key factor in inducing toxicity by amygdalin. Indeed, there is no guaranteed way to point out the microbial consortium for each person and provide a safe oral dosage. Recently, the encapsulating of amygdalin using alginate–chitosaninanoparticles (ACNPs) as transporter was investigated. As an active drug delivery mechanism for regulated and constant release of amygdalin with its enhanced cytotoxic effect on cancerous cells, biocompatible and biodegradable ACNPs can be applied while protectinginormal cells and tissues. In conclusion, still unproven and conflicting facts give way to a broad avenue of researchifor a compound that could potentially be the next stage of cancer therapy.

THYROID STIMULATORS AND THYROID STIMULATION

1971 ◽  
Vol 66 (3) ◽  
pp. 558-576 ◽  
Author(s):  
Gerald Burke
Keyword(s):  
Regulatory System ◽  
Control Site ◽  
Thyroid Cell ◽  
Primary Control ◽  
Physico Chemical ◽  
Site Of Action ◽  
Long Acting

ABSTRACT A long-acting thyroid stimulator (LATS), distinct from pituitary thyrotrophin (TSH), is found in the serum of some patients with Graves' disease. Despite the marked physico-chemical and immunologic differences between the two stimulators, both in vivo and in vitro studies indicate that LATS and TSH act on the same thyroidal site(s) and that such stimulation does not require penetration of the thyroid cell. Although resorption of colloid and secretion of thyroid hormone are early responses to both TSH and LATS, available evidence reveals no basic metabolic pathway which must be activated by these hormones in order for iodination reactions to occur. Cyclic 3′, 5′-AMP appears to mediate TSH and LATS effects on iodination reactions but the role of this compound in activating thyroidal intermediary metabolism is less clear. Based on the evidence reviewed herein, it is suggested that the primary site of action of thyroid stimulators is at the cell membrane and that beyond the(se) primary control site(s), there exists a multifaceted regulatory system for thyroid hormonogenesis and cell growth.

Nanodrugs as a new approach in therapy of cardiovascular diseases and cancer with tumor-associated angiogenesis

2020 ◽  
Vol 28 ◽  
Author(s):  
Justyna Hajtuch ◽  
Karolina Niska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Controlled Drug Release ◽  
Biological Properties ◽  
Comprehensive Information ◽  
Conventional Drug ◽  
Key Factor ◽  
Functionalized Materials

Background: Cancer along with cardiovascular diseases are globally defined as leading causes of death. Importantly, some risk factors are common to these diseases. The process of angiogenesis and platelets aggregation are observed in cancer development and progression. In recent years, studies have been conducted on nanodrugs in these diseases that have provided important information on the biological and physicochemical properties of nanoparticles. Their attractive features are that they are made of biocompatible, well-characterized and easily functionalized materials. Unlike conventional drug delivery, sustained and controlled drug release can be obtained by using nanomaterials. Methods: In this article, we review the latest research to provide comprehensive information on nanoparticle-based drugs for the treatment of cancer, cardiovascular disease associated with abnormal haemostasis, and the inhibition of tumorassociated angiogenesis. Results: The results of the analysis of data based on nanoparticles with drugs confirm their improved pharmaceutical and biological properties, which gives promising antiplatelet, anticoagulant and antiangiogenic effects. Moreover, the review included in vitro, in vivo research and presented nanodrugs with chemotherapeutics approved by Food and Drug Administration. Conclusion: By the optimization of nanoparticles size and surface properties, nanotechnology are able to deliver drugs with enhanced bioavailability in treatment of cardiovascular disease, cancer and inhibition of cancer-related angiogenesis. Thus, nanotechnology can improve the therapeutic efficacy of the drug, but there is a need for a better understanding of the nanodrugs interaction in the human body, because this is a key factor in the success of potential nanotherapeutics.

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