scholarly journals Solubility Determination of c-Met Inhibitor in Solvent Mixtures and Mathematical Modeling to Develop Nanosuspension Formulation

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 390
Author(s):  
Maharjan Ravi ◽  
Tripathi Julu ◽  
Nam Ah Kim ◽  
Kyeung Eui Park ◽  
Seong Hoon Jeong
Keyword(s):  
Mole Fraction ◽  
Effect Study ◽  
Solvent Mixtures ◽  
Water Mixture ◽  
The Mean ◽  
Met Inhibitor ◽  
Solubility Determination ◽  
Low Solubility

The solubility and dissolution thermodynamics of new c-Met inhibitor, ABN401, were determined in eleven solvents and Transcutol® HP–water mixture (TWM) from 298.15 to 318.15 K. The experimental solubilities were validated using five mathematical models, namely modified Apelblat, van’t Hoff, Buchowski–Ksiazaczak λh, Yalkowsky, and Jouyban–Acree van’t Hoff models. The experimental results were correlated and utilized further to investigate the feasibility of nanosuspension formation using liquid anti-solvent precipitation. Thermodynamic solubility of ABN401 increased significantly with the increase in temperature and maximum solubility was obtained with Transcutol® HP while low solubility in was obtained water. An activity coefficient study indicated that high molecular interaction was observed in ABN401–Transcutol® HP (THP). The solubility increased proportionately as the mole fraction of Transcutol® HP increased in TWM, which was also supported by a solvent effect study. The result suggested endothermic and entropy-driven dissolution. Based on the solubility, nanosuspension was designed with Transcutol® HP as solvent, and water as anti-solvent. The mean particle size of nanosuspension decreased to 43.05 nm when the mole fraction of ABN401 in THP, and mole fraction of ABN401 in TWM mixture were decreased to 0.04 and 0.1. The ultrasonicated nanosuspension appeared to give comparatively higher dissolution than micronized nanosuspension and provide a candidate formulation for in vivo purposes.

scholarly journals Measurement of Retinal Microvascular Blood Velocity Using Erythrocyte Mediated Velocimetry

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Breanna M. Tracey ◽  
Lakyn N. Mayo ◽  
Christopher T. Le ◽  
Victoria Y. Chen ◽  
Julian Weichsel ◽  
...  
Keyword(s):  
Average Diameter ◽  
Retinal Blood Flow ◽  
Direct Visualization ◽  
Ocular Diseases ◽  
Novel Technique ◽  
Retinal Microvasculature ◽  
The Mean ◽  
Pharmacologic Agents

AbstractChanges in retinal blood flow may be involved in the pathogenesis of glaucoma and other ocular diseases. Erythrocyte mediated velocimetry (EMV) is a novel technique where indocyanine green (ICG) dye is sequestered in erythrocyte ghosts and autologously re-injected to allow direct visualization of erythrocytes for in vivo measurement of speed. The purpose of this study is to determine the mean erythrocyte speed in the retinal microvasculature, as well as the intravisit and intervisit variability of EMV. Data from 23 EMV sessions from control, glaucoma suspect, and glaucoma patients were included in this study. In arteries with an average diameter of 43.11 µm ± 6.62 µm, the mean speed was 7.17 mm/s ± 2.35 mm/s. In veins with an average diameter of 45.87 µm ± 12.04 µm, the mean speed was 6.05 mm/s ± 1.96 mm/s. Intravisit variability, as measured by the mean coefficient of variation, was 3.57% (range 0.44–9.68%). Intervisit variability was 4.85% (range 0.15–8.43%). EMV may represent reliable method for determination of retinal blood speed, potentially allowing insights into the effects of pharmacologic agents or pathogenesis of ocular diseases.

Determination of the pH of Hemolyzed Packed Red Cells from Arterial Blood

1961 ◽  
Vol 7 (5) ◽  
pp. 536-541 ◽  
Author(s):  
May K Purcell ◽  
Gertrude M Still ◽  
Theodore Rodman ◽  
Henry P Close
Keyword(s):  
Blood Cell ◽  
Normal Subjects ◽  
The Body ◽  
Red Cell ◽  
Arterial Blood ◽  
Fiducial Probability ◽  
The Mean ◽  
Red Cell Ph

Abstract A technic is described for the determination of the in vivo pH of red blood cell hemolysates. The mean arterial red cell pH of 20 normal subjects was 7.19 with a range of 7.15 to 7.22. The fiducial probability at the 0.95 level is 7.13 to 7.25. The mean difference in pH between plasma and cells was 0.21, with a range of 0.15 to 0.23. It is suggested that changes in pH of erythrocytes may reflect changes in other less accessible cells of the body and that the determination may be a useful research and clinical procedure in the study of metabolic and respiratory derangements.

In Vivo Determination of Elastic Modulus of Canine Cardiac Muscle

1972 ◽  
Vol 94 (4) ◽  
pp. 912-916 ◽  
Author(s):  
J. F. Lafferty ◽  
E. P. McCutcheon ◽  
J. E. Funk ◽  
A. M. Higgins
Keyword(s):  
Elastic Modulus ◽  
Left Ventricle ◽  
Circumferential Stress ◽  
Isotonic Saline ◽  
Strain Analysis ◽  
Volume Data ◽  
Rapid Injection ◽  
The Mean

A practical technique was developed for in vivo determinations of the mechanical properties of canine left ventricle. A “quick stretch” was accomplished by rapid injection of isotonic saline into the ventricle during isovolumetric systole. The experimental pressure-volume data and a stress-strain analysis of the left ventricle as a thick-walled sphere permitted determination of the effective elastic modulus as a function of the mean circumferential stress. The elastic modulus E was found to be a linear function of the mean tangential stress σ throughout the isovolumetric systolic period; the slope (K, modulus of stiffness) of the Eversus σ curve was 18.8 with a standard deviation of 0.9.

In Vitro and In Situ Absorption and Metabolism of Sesquiterpenes from Petasites hybridus Extracts

Planta Medica ◽  
2018 ◽  
Vol 84 (11) ◽  
pp. 795-805
Author(s):  
Lucia Disch ◽  
Kristina Forsch ◽  
Beate Siewert ◽  
Jürgen Drewe ◽  
Gert Fricker
Keyword(s):  
Hepatic Metabolism ◽  
Absorption Capacity ◽  
Active Constituent ◽  
In Situ Absorption ◽  
Low Solubility ◽  
S9 Fraction

Abstract Petasites hybridus extract is used in the treatment of seasonal allergic rhinitis. The aim of this study was to evaluate the active constituent petasin and its isomers isopetasin and neopetasin (petasins) in the P. hybridus extract Ze 339 for liberation, dissolution, absorption, and metabolism. The determination of pH-dependent thermodynamic solubility was performed via the shake-flask method. Petasins exhibited a low solubility that was pH independent. In vivo, the concentration of solute drugs is decreased continuously by intestinal absorption. Therefore, low solubility is not assumed to be critical for in vivo performance. Additionally, dissolution of an herbal medicinal product containing P. hybridus extract Ze 339 was assessed. Furthermore, high permeability through Caco-2 monolayers was evident. Using an in situ rat model, absorption capacity for petasins was found in all tested intestinal segments, namely, duodenum, jejunum, and ileum. Besides, high metabolism was evident both in Caco-2 monolayers and in the rat intestine. To compare intestinal and hepatic metabolism of petasins, in vitro enzyme assays using liver and intestinal cytosol and microsomes (S9 fraction) of rats and humans were performed. A significantly higher metabolic rate was found in the liver S9 fraction of both species compared with the intestinal S9 fraction.

scholarly journals Tissue Penetration and Pharmacokinetics of Tigecycline in Diabetic Patients with Chronic Wound Infections Described by Using In Vivo Microdialysis

2010 ◽  
Vol 54 (12) ◽  
pp. 5209-5213 ◽  
Author(s):  
Catharine C. Bulik ◽  
Dora E. Wiskirchen ◽  
Ashley Shepard ◽  
Christina A. Sutherland ◽  
Joseph L. Kuti ◽  
...  
Keyword(s):  
Steady State ◽  
Protein Binding ◽  
Subcutaneous Tissue ◽  
Diabetic Patients ◽  
Tissue Penetration ◽  
Tissue Concentrations ◽  
Time Curve ◽  
The Mean

ABSTRACT Tissue penetration of systemic antibiotics is an important consideration for positive outcomes in diabetic patients. Herein we describe the exposure profile and penetration of tigecycline in the interstitial fluid of wound margins versus that of uninfected thigh tissue in 8 adult diabetic patients intravenously (IV) administered 100 mg and then 50 mg of tigecycline twice daily for 3 to 5 doses. Prior to administration of the first dose, 2 microdialysis catheters were inserted into the subcutaneous tissue, the first within 10 cm of the wound margin and the second in the thigh of the same extremity. Samples for determination of plasma and tissue concentrations were simultaneously collected over 12 h under steady-state conditions. Tissue concentrations were corrected for percent in vivo recovery by the retrodialysis technique. Plasma samples were also collected for determination of protein binding at 1, 6, and 12 h postdose for each patient. Protein binding data were corrected using a fitted polynomial equation. The mean patient weight was 95.1 kg (range, 63.6 to 149.2 kg), the mean patient age was 63.5 ± 9.4 years, and 75% of the patients were males. The mean values for the plasma, thigh, and wound free area under the concentration-time curve from 0 to 24 h (fAUC0-24) were 2.65 ± 0.33, 2.52 ± 1.15, and 2.60 ± 1.02 μg·h/ml, respectively. Protein binding was nonlinear, with the percentage of free drug increasing with decreasing serum concentrations. Exposure values for thigh tissue and wound tissue were similar (P = 0.986). Mean steady-state tissue concentrations for the thigh and wound were similar at 0.12 ± 0.02 μg/ml, and clearance from the tissues appeared similar to that from plasma. Tissue penetration ratios (tissue fAUC/plasma fAUC) were 99% in the thigh and 100% in the wound (P = 0.964). Tigecycline penetrated equally well into wound and uninfected tissue of the same extremity.

METHOD DEVELOPMENT AND VALIDATION OF VALACYCLOVIR HYDROCHLORIDE AND RITONAVIR IN TABLET DOSAGE FORM USING REVERSE PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

2015 ◽  
Vol 76 (1) ◽  
Author(s):  
D. Sathis Kumar ◽  
B. D. N Prashanthi ◽  
A. Harani ◽  
P. Anusha
Keyword(s):  
High Performance ◽  
Dosage Form ◽  
Method Development ◽  
Hplc Method ◽  
Water Mixture ◽  
Method Development And Validation ◽  
The Mean ◽  
Development And Validation ◽  
Tablet Dosage

Our main objective is to develop an accurate and precise RP-HPLC method for the simultaneous determination of Valacyclovir HCl and Ritonavir in tablet dosage form. An Agilent TC-C18 (2) column is used for the Separation of drugs by a mobile phase consisting of methanol, acetonitrile and water mixture in the ratio of 35:41.5:23.5v/v. The flow rate maintained was 1.3 mL/min and the wavelength used for detection was 222 nm. The linearity was observed in the range of 12.5-125µg/ml for Valacyclovir HCl (VC) and Ritonavir (RT) with a correlation coefficient of 0.9987 and 0.9981 respectively. The mean percentage recoveries for 80%, 100% and 120% accuracy were found to be 101.7%±2.09, 100%±2.49 and 101.5%±1.61 respectively for VC. The mean percentage recoveries for 80%, 100% and 120% accuracy were found to be 104.3%±0.99, 100%±1.77and 99.0%±1.22 respectively for RT. Linearity, accuracy, precision and robustness parameters for the suggested method were estimated for validation. The developed method can be utilized in the analysis of VC and RT tablets.

Solvent dependent swelling behaviour of poly(N-vinylcaprolactam) and poly(N-vinylcaprolactam-co-itaconic acid) gels and determination of solubility parameters

2015 ◽  
Vol 69 (10) ◽  
Author(s):  
Selva Çavuş ◽  
Elçin Çakal ◽  
Lutfullah M. Sevgili
Keyword(s):  
Itaconic Acid ◽  
Isopropyl Alcohol ◽  
Solubility Parameters ◽  
Cross Linking ◽  
Binary Solvent ◽  
Solvent Mixtures ◽  
Water Mixture ◽  
Swelling Behaviour ◽  
Cross Linker

AbstractSwelling behaviour of poly(N-vinylcaprolactam) (PVC) and poly(N-vinylcaprolactam-co-itaconic acid) (P(VC-co-IA)) gels was investigated in different solvents (water, ethanol, methanol, isopropyl alcohol (IPA), chloroform, toluene, acetone) and in binary solvent mixtures (ethanol/chloroform, ethanol/methanol, IPA/chloroform, ethanol/water, IPA/water). Gels were synthesised in ethanol by the free radical cross-linking polymerisation method at 60°C for 24 h in the presence of azobis( isobutyronitrile) and allyl methacrylate as the initiator and cross-linker, respectively. And also, ethanol/distilled water mixture (φ

Evaluation of Potential Analytical Approach for Determination of Polychlorinated Biphenyls in Serum: Interlaboratory Study

1983 ◽  
Vol 66 (4) ◽  
pp. 956-968
Author(s):  
Virlyn W Burse ◽  
Larry L Needham ◽  
Chester R Lapeza ◽  
Margaret P Korver ◽  
John A Liddle ◽  
...  
Keyword(s):  
Polychlorinated Biphenyls ◽  
Ethyl Ether ◽  
Analytical Approach ◽  
Chromatographic Determination ◽  
Electron Capture Detection ◽  
Coefficients Of Variation ◽  
The Mean

Abstract Forty-four laboratories participated in evaluation of a method for determining polychlorinated biphenyls (PCBs) as AR 1254 in serum at the parts per billion level. The method involves deproteinating serum with methanol, extracting with hexane-ethyl ether, and eluting PCBs from deactivated silica gel for gasliquid chromatographic determination with electron capture detection. Compounds are quantitated by using the Webb-McCall factors. Five serum pools, 4 containing in vivo-fortified PCBs (as AR 1254) or 8 in vitro-f ortif ied chlorinated hydrocarbons (CHs), or both, were used. For PCB fortification levels of 9.89 (EP 2), 24.74 (EP 3), and 74.20 ppb (EP 4), interlaboratory coefficients of variation (CVs) for collaborators that adhered to protocol were 92.7, 67.6, and 25.8%, respectively. CVs on the same pools analyzed by the Centers for Disease Control (CDC) were 7.4, 7.8, and 4.6%, respectively. Average interlaboratory recoveries for pools EP 2, EP 3, and EP 4 were 138.1,111.2, and 91.1%, respectively, and 99.8,89.6, and 90.4%, respectively, for CDC on the same pools. There was a general decrease in the mean error for those laboratories that had participated in an earlier study in which they were allowed to use their own methods.

scholarly journals Determination of Freeway Space in Completely Edentulous Patients Using Lateral Profile Photographs—In Vivo Study

2019 ◽  
Vol 05 (01) ◽  
pp. 006-009
Author(s):  
Monika Dagdiya ◽  
Ashok Pakhan ◽  
Surekha Dubey ◽  
Seema Sathe ◽  
Manish Dagdiya
Keyword(s):  
Significant Negative Correlation ◽  
Reference Points ◽  
Simple Linear Regression ◽  
Prediction Formula ◽  
Independent Variable ◽  
The Mean ◽  
Edentulous Patients ◽  
Lateral Profile

Abstract Objective This study aims to determine the freeway space (FWS) using lateral profile photograph (LPP) as an adjunct in completely edentulous patients. Materials and Methods In this study, 30 patients in the age group of 45 to 60 years who met with the criteria were included. LPPs were taken for all participants using standard protocol and a duplicate copy was obtained, on which three soft tissue reference points—porion (Stp), gnathion (Stgn), and gonion (Stg)—were marked and joined to form an angle Stp-Stg-Stgn. This angle was correlated with the mean FWS obtained using swallowing. Simple linear regression model was used to develop a prediction formula for FWS using Stp-Stg-Stgn angle as the independent variable. Result This study shows that the angle Stp-Stg-Stgn had a significant negative correlation with FWS.

Statistical constraints on microvascular measurements using fluorescent erythrocytes

1985 ◽  
Vol 248 (4) ◽  
pp. H577-H586 ◽  
Author(s):  
I. H. Sarelius ◽  
S. M. McKinlay
Keyword(s):  
Simultaneous Determination ◽  
Coefficient Of Variation ◽  
Fluorescent Cell ◽  
Cell Counts ◽  
Cell Velocity ◽  
In Vivo Sampling ◽  
Sampling Intervals ◽  
The Mean

We show that two separate estimators of microvessel hematocrit (H) using the same fluorescent cell technique are not equally precise. The precision of H (indicated by the coefficient of variation, CV) depends on in vivo labeled cell counts (m), the labeled fraction (p), and for time-averaged H estimates, the mean cell velocity (v). Thus, for length-dependent estimates of H, CV2(HL) = 1/E(m) + CV2(p) and for time-averaged H estimates, CV2(Ht) = 1/E(m) + CV2(p) + CV2(v). Because CV(p) can be made small arbitrarily and independently, the precision of H is principally dependent on the expected value of m. Practical sampling constraints and minimum sampling intervals are identified and used to define strategies to minimize CV(H). We show that Ht is preferable to HL because it is more precise and the useful in vivo sampling range of m and p is more flexible. In addition, Ht allows simultaneous determination of cell flux and mean cell velocity.

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