In vitro investigation on the impact of airway mucus on drug dissolution and absorption at the air-epithelium interface in the lungs

Abstract Paediatric medicines are not always age-appropriate, causing problems with dosing, acceptability and adherence. The use of food and drinks as vehicles for medicine co-administration is common practice, yet the impact on drug bioavailability, safety and efficacy remains unaddressed. The aim of this study was to use in vitro dissolution testing, under infant simulating conditions, to evaluate the effect of co-administration with vehicles on the dissolution performance of two poorly soluble paediatric drugs. Dissolution studies of mesalazine and montelukast formulations were conducted with mini-paddle apparatus on a two-stage approach: simulated gastric fluid followed by addition of simulated intestinal fluid. The testing scenarios were designed to reflect daily administration practices: direct administration of formulation; formulation co-administered with food and drinks, both immediately after mixing and 4 h after mixing. Drug dissolution was significantly affected by medicine co-administration with vehicles, compared to the direct administration of formulation. Furthermore, differences were observed on drug dissolution when the formulations were mixed with different vehicles of the same subtype. The time between preparation and testing of the drug-vehicle mixture also impacted dissolution behaviour. Drug dissolution was shown to be significantly affected by the physicochemical properties and composition of the vehicles, drug solubility in each vehicle and drug/formulation characteristics. Ultimately, in this study, we show the potential of age-appropriate in vitro dissolution testing as a useful biopharmaceutical tool for estimating drug dissolution in conditions relevant to the paediatric population. The setup developed has potential to evaluate the impact of medicine co-administration with vehicles on paediatric formulation performance.

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In vitro investigation of the impact of remaining tooth structure on the tensile failure loads of overdenture copings

Journal of Clinical and Experimental Dentistry ◽

10.4317/jced.56228 ◽

2019 ◽

pp. 0-0

Author(s):

A Fotiou ◽

SN Kamalakidis ◽

AL Pissiotis ◽

K Michalakis

Keyword(s):

Tensile Failure ◽

Tooth Structure ◽

In Vitro Investigation ◽

Failure Loads ◽

The Impact

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Development of an In Vitro System to Study the Interactions of Aerosolized Drugs with Pulmonary Mucus

Pharmaceutics ◽

10.3390/pharmaceutics12020145 ◽

2020 ◽

Vol 12 (2) ◽

pp. 145 ◽

Cited By ~ 2

Author(s):

Safar Alqahtani ◽

Clive J. Roberts ◽

Snjezana Stolnik ◽

Cynthia Bosquillon

Keyword(s):

Drug Disposition ◽

Fluorescent Dyes ◽

Thin Layers ◽

Inhaled Drugs ◽

Upper Airways ◽

In Vitro System ◽

Unique Parameter ◽

Airway Mucus ◽

The Impact

Mucus is the first biological component inhaled drugs encounter on their journey towards their pharmacological target in the upper airways. Yet, how mucus may influence drug disposition and efficacy in the lungs has been essentially overlooked. In this study, a simple in vitro system was developed to investigate the factors promoting drug interactions with airway mucus in physiologically relevant conditions. Thin layers of porcine tracheal mucus were prepared in Transwell® inserts and initially, the diffusion of various fluorescent dyes across those layers was monitored over time. A deposition system featuring a MicroSprayer® aerosolizer was optimized to reproducibly deliver liquid aerosols to multiple air-facing layers and then exploited to compare the impact of airway mucus on the transport of inhaled bronchodilators. Both the dyes and drugs tested were distinctly hindered by mucus with high logP compounds being the most affected. The diffusion rate of the bronchodilators across the layers was in the order: ipratropium ≈ glycopyronnium > formoterol > salbutamol > indacaterol, suggesting hydrophobicity plays an important role in their binding to mucus but is not the unique parameter involved. Testing of larger series of compounds would nevertheless be necessary to better understand the interactions of inhaled drugs with airway mucus.

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In vitro investigation on the impact of the surface-active excipients Cremophor EL, Tween 80 and Solutol HS 15 on the metabolism of midazolam

Biopharmaceutics & Drug Disposition ◽

10.1002/bdd.383 ◽

2004 ◽

Vol 25 (1) ◽

pp. 37-49 ◽

Cited By ~ 61

Author(s):

Roberto C. Bravo González ◽

Jörg Huwyler ◽

Franziska Boess ◽

Isabelle Walter ◽

Beate Bittner

Keyword(s):

Tween 80 ◽

Cremophor El ◽

In Vitro Investigation ◽

Surface Active ◽

Solutol Hs 15 ◽

The Impact

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In Vivo Predictive Dissolution Testing of Montelukast Sodium Formulations Administered with Drinks and Soft Foods to Infants

AAPS PharmSciTech ◽

10.1208/s12249-020-01825-7 ◽

2020 ◽

Vol 21 (7) ◽

Author(s):

J. Martir ◽

T. Flanagan ◽

J. Mann ◽

N. Fotaki

Keyword(s):

Drug Product ◽

Drug Dissolution ◽

Simulated Gastric Fluid ◽

Dissolution Testing ◽

Fed State ◽

Fasted State ◽

Direct Administration ◽

The Impact

Abstract In vitro dissolution testing conditions that reflect and predict in vivo drug product performance are advantageous, especially for the development of paediatric medicines, as clinical testing in this population is hindered by ethical and technical considerations. The aim of this study was to develop an in vivo predictive dissolution test in order to investigate the impact of medicine co-administration with soft food and drinks on the dissolution performance of a poorly soluble compound. Relevant in vitro dissolution conditions simulating the in vivo gastrointestinal environment of infants were used to establish in vitro-in vivo relationships with corresponding in vivo data. Dissolution studies of montelukast formulations were conducted with mini-paddle apparatus on a two-stage approach: infant fasted-state simulated gastric fluid (Pi-FaSSGF; for 1 h) followed by either infant fasted-state or infant fed-state simulated intestinal fluid (FaSSIF-V2 or Pi-FeSSIF, respectively; for 3 h). The dosing scenarios tested reflected in vivo paediatric administration practices: (i.) direct administration of formulation; (ii.) formulation co-administered with vehicles (formula, milk or applesauce). Drug dissolution was significantly affected by co-administration of the formulation with vehicles compared with after direct administration of the formulation. Montelukast dissolution from the granules was significantly higher under fed-state simulated intestinal conditions in comparison with the fasted state and was predictive of the in vivo performance when the granules are co-administered with milk. This study supports the potential utility of the in vitro biorelevant dissolution approach proposed to predict in vivo formulation performance after co-administration with vehicles, in the paediatric population.

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INFLUENCE OF FORMULATION PARAMETERS ON DISSOLUTION RATE ENHANCEMENT OF ACYCLOVIR USING LIQUISOLID FORMULATION

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11s2.28537 ◽

2018 ◽

Vol 11 (14) ◽

pp. 36

Author(s):

Kubota Mwaka Hazemba ◽

Jivan Jyoti ◽

Sheetu Wadhwa ◽

Sananda Som ◽

Souvik Mohanta ◽

...

Keyword(s):

Dissolution Rate ◽

Research Work ◽

Drug Dissolution ◽

Dissolution Rate Enhancement ◽

Liquid Medication ◽

Formulation Parameters ◽

Tween 60 ◽

Rate Profile ◽

The Impact

Objective: The objective of this research work is to explore the use of liquisolid technique in enhancement of acyclovir dissolution rate. This current study was planned to assess the impact of different formulation variables, such as non-volatile liquid type and concentrations of acyclovir on its dissolution rates profile. Method: Acyclovir liquisolid tablets were prepared with Tween 60 (liquid vehicle), Microcrystalline cellulose PH 102 (acted as a carrier to turn liquid medication into free-flowing powder) and Syloid XDP (coating material). In vitro, drug dissolution rate of liquisolid formulations of acyclovir was performed and compared with pure acyclovir drug using USP dissolution apparatus (Type II) for 60 min at a paddle speed of 50 rpm and filled with 900 mL of distilled water. Results: The dissolution study showed that 94.1% of the drug was released in 60 min of ratio 10 while only 66% of the pure drug acyclovir was released in 60 min. Hence, present work concluded that the acyclovir dissolution rate profile has been improved with the formation of liquisolid formulations. Conclusion: From the present study, it may be ratified that the drug dissolution rate of acyclovir has been improved with the utilization of liquisolid formulations approach.

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In vitro investigation of the impact of pulsatile blood flow on the vascular architecture of decellularized porcine kidneys

Scientific Reports ◽

10.1038/s41598-021-95924-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Peter R. Corridon

Keyword(s):

Blood Flow ◽

Blood Perfusion ◽

Pulsatile Blood Flow ◽

Venous Outflow ◽

Venous Flow ◽

Vascular Architecture ◽

Arterial Perfusion ◽

In Vitro Investigation ◽

The Impact

AbstractA method was established using a scaffold-bioreactor system to examine the impact pulsatile blood flow has on the decellularized porcine kidney vascular architecture and functionality. These scaffolds were subjected to continuous arterial perfusion of whole blood at normal physiological (650 ml/min and 500 ml/min) and pathophysiological (200 ml/min) rates to examine dynamic changes in venous outflow and micro-/macrovascular structure and patency. Scaffolds subjected to normal arterial perfusion rates observed drops in venous outflow over 24 h. These reductions rose from roughly 40% after 12 h to 60% after 24 h. There were no apparent signs of clotting at the renal artery, renal vein, and ureter. In comparison, venous flow rates decreased by 80% to 100% across the 24 h in acellular scaffolds hypoperfused at a rate of 200 ml/min. These kidneys also appeared intact on the surface after perfusion. However, they presented several arterial, venous, and ureteral clots. Fluoroscopic angiography confirmed substantial alterations to normal arterial branching patterns and patency, as well as parenchymal damage. Scanning electron microscopy revealed that pulsatile blood perfusion significantly disrupted glomerular microarchitecture. This study provides new insight into circumstances that limit scaffold viability and a simplified model to analyze conditions needed to prepare more durable scaffolds for long-term transplantation.

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Impact of Horse Hoof Wall with Different Solid Surfaces

Applied Sciences ◽

10.3390/app10238743 ◽

2020 ◽

Vol 10 (23) ◽

pp. 8743

Author(s):

Jing Zhao ◽

Dan B. Marghitu ◽

John Schumacher ◽

Wenzhong Wang

Keyword(s):

Contact Force ◽

Coefficient Of Friction ◽

Coefficient Of Restitution ◽

Solid Surfaces ◽

Effective Coefficient ◽

In Vitro Investigation ◽

Equine Hoof ◽

Impact Angles ◽

The Impact

This study aimed to investigate the impact of a horse hoof wall on three solid surfaces: steel, concrete and asphalt. Impact experiments were conducted for different impact angles and different initial impact velocities. The effect of impact surfaces, impact angles and initial impact velocities on the coefficient of restitution and the effective coefficient of friction were tested using one-way ANOVA. Analytical and numerical modeling of the impact were developed. The impact interval was divided into two phases: compression and restitution. For compression, a contact force with a damping term was used. The restitution was characterized by an elastic contact force. The stiffness and damping coefficients of the contact force were estimated from the normal impacts. The simulated velocities after the oblique impacts were compared to the velocities in the in vitro investigation. The coefficient of restitution varied significantly on different surfaces. The effective coefficient of friction was lower on steel compared to concrete and asphalt. The model presented in this study can be applied to refine the impact simulation of the equine hoof during locomotion.

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In vitro investigation on the impact of Solutol HS 15 on the uptake of colchicine into rat hepatocytes

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2004.04.010 ◽

2004 ◽

Vol 279 (1-2) ◽

pp. 27-31 ◽

Cited By ~ 7

Author(s):

Roberto Carlos Bravo González ◽

Franziska Boess ◽

Evelyne Durr ◽

Nathalie Schaub ◽

Beate Bittner

Keyword(s):

Rat Hepatocytes ◽

In Vitro Investigation ◽

Solutol Hs 15 ◽

The Impact

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An in vitro investigation to understand the synergistic role of MMPs-1 and 9 on articular cartilage biomechanical properties

Scientific Reports ◽

10.1038/s41598-021-93744-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Allison Mixon ◽

Andrew Savage ◽

Ahmed Suparno Bahar-Moni ◽

Malek Adouni ◽

Tanvir Faisal

Keyword(s):

Peak Load ◽

Biomechanical Properties ◽

Cartilage Degradation ◽

Enzyme Concentration ◽

Cartilage Explants ◽

Healthy State ◽

In Vitro Investigation ◽

Degradative Enzymes ◽

The Impact

AbstractMatrix metalloproteinases (MMPs) play a crucial role in enzymatically digesting cartilage extracellular matrix (ECM) components, resulting in degraded cartilage with altered mechanical loading capacity. Overexpression of MMPs is often caused by trauma, physiologic conditions and by disease. To understand the synergistic impact MMPs have on cartilage biomechanical properties, MMPs from two subfamilies: collagenase (MMP-1) and gelatinase (MMP-9) were investigated in this study. Three different ratios of MMP-1 (c) and MMP-9 (g), c1:g1, c3:g1 and c1:g3 were considered to develop a degradation model. Thirty samples, harvested from bovine femoral condyles, were treated in groups of 10 with one concentration of enzyme mixture. Each sample was tested in a healthy state prior to introducing degradative enzymes to establish a baseline. Samples were subjected to indentation loading up to 20% bulk strain. Both control and treated samples were mechanically and histologically assessed to determine the impact of degradation. Young’s modulus and peak load of the tissue under indentation were compared between the control and degraded cartilage explants. Cartilage degraded with the c3:g1 enzyme concentration resulted in maximum 33% reduction in stiffness and peak load compared to the other two concentrations. The abundance of collagenase is more responsible for cartilage degradation and reduced mechanical integrity.

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