Oral relative bioavailability of Dichlorodiphenyltrichloroethane (DDT) in contaminated soil and its prediction using in vitro strategies for exposure refinement

2021 ◽

Vol 9 ◽

pp. 2050313X2110349

Author(s):

Brett D Edwards ◽

Ranjani Somayaji ◽

Dina Fisher ◽

Justin C Chia

Keyword(s):

Case Report ◽

Chronic Lung Disease ◽

Contaminated Soil ◽

Lung Abscess ◽

Immunocompetent Individual ◽

First Case ◽

Antimycobacterial Agents ◽

Vitro Data ◽

In Vitro Data

Mycobacterium elephantis was first described when isolated from an elephant that succumbed to lung abscess. However, despite this namesake, it is not associated with animals and has been described most often as a probable colonizer rather than pathogen in humans with chronic lung disease. In this report, we describe the first case of lymphocutaneous infection from M. elephantis, likely as a result of cutaneous inoculation with contaminated soil. This offers further evidence to its capabilities as a pathogen. We provide a review of the limited prior reports of M. elephantis and outline the available in vitro data on efficacy of various antimycobacterial agents.

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Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technology

Acta Pharmaceutica ◽

10.2478/v10007-009-0010-2 ◽

2009 ◽

Vol 59 (1) ◽

pp. 15-30 ◽

Cited By ~ 6

Author(s):

Pramod Kumar ◽

Sanjay Singh ◽

Brahmeshwar Mishra

Keyword(s):

Drug Release ◽

Extended Release ◽

Relative Bioavailability ◽

Pharmacokinetic Parameters ◽

Healthy Human ◽

Tramadol Hydrochloride ◽

Release Formulation ◽

Extended Release Formulation

Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technologyExtended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media.In vivostudy was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax,tmax,AUC0-24,MRT) and relative bioavailability were calculated. Thein vitroandin vivoresults were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation.In vitro-in vivocorrelation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R= 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.

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Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer

Pharmaceutics ◽

10.3390/pharmaceutics13101560 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1560

Author(s):

Amr Gamal ◽

Haitham Saeed ◽

Fatma I. Abo El-Ela ◽

Heba F. Salem

Keyword(s):

Steady State ◽

Skin Cancer ◽

Entrapment Efficiency ◽

The United States ◽

Relative Bioavailability ◽

Passive Targeting ◽

Therapeutic Benefits ◽

Steady State Flux

Throughout the United States and the world, skin cancer is the most frequent form of cancer. Sonidegib (SNG) is a hedgehog inhibitor that has been used for skin cancer treatment. However, SNG has low bioavailability and is associated with resistance. The focus of this work is to enhance bioavailability, anti-tumor efficacy and targeting of SNG via developing ethosome gel as a potential treatment for skin cancer. SNG-loaded ethosomes formulation was prepared and characterized in vitro by %entrapment efficiency (%EE), vesicle size, morphology, %release and steady-state flux. The results showed that the prepared formulation was spherical nanovesicles with a %EE of 85.4 ± 0.57%, a particle size of 199.53 ± 4.51 nm and a steady-state flux of 5.58 ± 0.08 µg/cm2/h. In addition, SNG-loaded ethosomes formulation was incorporated into carbopol gel to study the anti-tumor efficacy, localization and bioavailability in vivo. Compared with oral SNG, the formulation showed 3.18 times higher relative bioavailability and consequently significant anti-tumor activity. In addition, this formulation showed a higher rate of SNG penetration in the skin’s deep layers and passive targeting in tumor cells. Briefly, SNG-loaded ethosome gel can produce desirable therapeutic benefits for treatment of skin cancer.

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Physiologically Relevant In Vitro-In Vivo Correlation (IVIVC) Approach for Sildenafil with Site-Dependent Dissolution

Pharmaceutics ◽

10.3390/pharmaceutics11060251 ◽

2019 ◽

Vol 11 (6) ◽

pp. 251 ◽

Cited By ~ 4

Author(s):

Tae Hwan Kim ◽

Soyoung Shin ◽

Seok Won Jeong ◽

Jong Bong Lee ◽

Beom Soo Shin

Keyword(s):

Dissolution Kinetics ◽

Immediate Release ◽

Relative Bioavailability ◽

Wet Granulation ◽

Population Pharmacokinetic ◽

Beagle Dogs ◽

Concentration Time ◽

In Vivo Dissolution

This study aimed to establish a physiologically relevant in vitro-in vivo correlation (IVIVC) model reflecting site-dependent dissolution kinetics for sildenafil based on population-pharmacokinetic (POP-PK) modeling. An immediate release (IR, 20 mg) and three sustained release (SR, 60 mg) sildenafil tablets were prepared by wet granulation method. In vitro dissolutions were determined by the paddle method at pH 1.2, 4.5, and 6.8 media. The in vivo pharmacokinetics were assessed after oral administration of the prepared IR and SR formulations to Beagle dogs (n = 12). The dissolution of sildenafil from SR formulations was incomplete at pH 6.8, which was not observed at pH 1.2 and pH 4.5. The relative bioavailability was reduced with the decrease of the dissolution rate. Moreover, secondary peaks were observed in the plasma concentration-time curves, which may result from site-dependent dissolution. Thus, a POP-PK model was developed to reflect the site-dependent dissolution by separately describing the dissolution and absorption processes, which allowed for estimation of the in vivo dissolution of sildenafil. Finally, an IVIVC was established and validated by correlating the in vitro and in vivo dissolution rates. The present approach may be applied to establish IVIVC for various drugs with complex dissolution kinetics for the development of new formulations.

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Relationship between Pb relative bioavailability and bioaccessibility in phosphate amended soil: Uncertainty associated with predicting Pb immobilization efficacy using in vitro assays

Environment International ◽

10.1016/j.envint.2019.104967 ◽

2019 ◽

Vol 131 ◽

pp. 104967 ◽

Cited By ~ 7

Author(s):

Farzana Kastury ◽

Silvia Placitu ◽

John Boland ◽

Ranju R. Karna ◽

Kirk G. Scheckel ◽

...

Keyword(s):

Relative Bioavailability ◽

In Vitro Assays ◽

Pb Immobilization ◽

Amended Soil

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Bioaccessibility of Arsenic Bound to Corundum Using a Simulated Gastrointestinal System

Environmental Chemistry ◽

10.1071/en05067 ◽

2006 ◽

Vol 3 (3) ◽

pp. 208 ◽

Cited By ~ 8

Author(s):

Douglas G. Beak ◽

Nicholas T. Basta ◽

Kirk G. Scheckel ◽

Samuel J. Traina

Keyword(s):

Gastrointestinal Tract ◽

Contaminated Soil ◽

Binding Capacity ◽

In Vitro Assay ◽

Oxide Surfaces ◽

Vitro Assay ◽

Edge Structure ◽

X Ray ◽

X Ray Absorption

Environmental Context. Ingestion of soil contaminated with arsenic is an important pathway for human exposure to arsenic. The risk posed by ingestion of arsenic-contaminated soil depends on how much arsenic is dissolved in the gastrointestinal tract. Aluminum oxides are common components in the soil and act as a sink for arsenic. Knowledge of the behavior of arsenic associated with aluminum oxide surfaces in a simulated gastrointestinal tract will provide an understanding of the ingestion risk of arsenic-contaminated soil to humans. Abstract. Arsenate adsorbed to oxide surfaces may influence the risk posed by incidental ingestion of arsenic-contaminated soil. Arsenate sorbed to corundum (α-Al2O3), a model Al oxide, was used to simulate ingested soil that has AsV sorbed to Al oxides. An in vitro assay was used to simulate the gastrointestinal tract and ascertain the bioaccessibility of arsenate bound to corundum. The surface speciation of arsenate was determined using extended X-ray absorption fine structure and X-ray absorption near edge structure spectroscopy. The arsenate sorption maximum was found to be 470 mg kg–1 and the surface speciation of the sorbed arsenate was inner-sphere binuclear bidenate. The AsV was found to only be bioaccessible during the gastric phase of the in vitro assay. When the sorbed AsV was <470 mg kg–1 (i.e., the sorption maxima) the bioaccessible As was below detection levels, but when sorbed AsV was ≥470 mg kg–1 the bioaccessible As ranged from 9 to 16%. These results demonstrate that the bioaccessibility of arsenate is related to the concentration and the arsenate binding capacity of the binding soil.

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