Enhanced Trans-Corneal Permeability of Valacyclovir by Polymethacrylic Acid Copolymers Based Ocular Microspheres: In Vivo Evaluation of Estimated Pharmacokinetic/Pharmacodynamic Indices and Simulation of Aqueous Humor Drug Concentration-Time Profile

Suvarna Bhasma (SB) is a gold particle-based medicine that is used in Ayurved to treat tuberculosis, arthritis and nervous diseases. Traditionally, the Ayurved preparation processes of SB do exist, but they are all long, tedious and involve several steps. Due to this, there is a possibility of bypassing the necessary Ayurved processes or non-adherence to all steps or use of synthetic gold particles. Our aim is to characterize 5 commercial SB preparations from 5 different manufacturers. A comparative physicochemical, pharmacokinetic (PK) and bioaccumulation study was carried out on all the 5 SB preparations. The general appearance such as color and texture of these 5 samples were different from each other. The size, shape and gold concentration (from 32-98 wt%) varied among all the 5 SBs. The accumulation of ionic gold in zebrafish and gold concentration profiles in rat blood were found to be significantly different for all the 5 SBs. Non-compartmental PK model obtained from the concentration-time profile showed significant differences in various PK parameters such as peak concentration (Cmax), half-life (t1/2) and terminal elimination slope (λz) for all the 5 SB preparations. SB-B showed the highest Cmax (8.55 μg/L), whereas SB-D showed the lowest Cmax (4.66 μg/L). The dissolution of ionic gold from SBs in zebrafish tissue after the oral dose had a 5.5-fold difference between the highest and lowest ionic gold concentrations. All the 5 samples showed distinct physicochemical and biological properties. Based on characteristic microscopic morphology, it was found that 2 preparations among them were suspected of being manufactured by non-adherence to the mentioned Ayurved references.

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Use of an In Vitro Pharmacodynamic Model To Derive a Linezolid Regimen That Optimizes Bacterial Kill and Prevents Emergence of Resistance in Bacillus anthracis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01439-07 ◽

2008 ◽

Vol 52 (7) ◽

pp. 2486-2496 ◽

Cited By ~ 29

Author(s):

A. Louie ◽

H. S. Heine ◽

K. Kim ◽

D. L. Brown ◽

B. VanScoy ◽

...

Keyword(s):

Bacillus Anthracis ◽

Drug Concentration ◽

Human Subjects ◽

Time Profile ◽

Pharmacodynamic Model ◽

Dose Fractionation ◽

Serum Drug Concentration ◽

Maximum Serum ◽

Concentration Time

ABSTRACT Simulating the average non-protein-bound (free) human serum drug concentration-time profiles for linezolid in an in vitro pharmacodynamic model, we characterized the pharmacodynamic parameter(s) of linezolid predictive of kill and for prevention of resistance in Bacillus anthracis. In 10-day dose-ranging studies, the average exposure for ≥700 mg of linezolid given once daily (QD) resulted in >3-log CFU/ml declines in B. anthracis without resistance selection. Linezolid at ≤600 mg QD amplified for resistance. With twice-daily (q12h) dosing, linezolid at ≥500 mg q12 h was required for resistance prevention. In dose fractionation studies, killing of B. anthracis was predicted by the area under the time-concentration curve (AUC)/MIC ratio. However, resistance prevention was linked to the maximum serum drug concentration (C max)/MIC ratio. Monte Carlo simulations predicted that linezolid at 1,100 mg QD would produce in 96.7% of human subjects a free 24-h AUC that would match or exceed the average 24-h AUC of 78.5 mg·h/liter generated by linezolid at 700 mg QD while reproducing the shape of the concentration-time profile for this pharmacodynamically optimized regimen. However, linezolid at 700 mg q12h (cumulative daily dose of 1,400 mg) would produce an exposure that would equal or exceed the average free 24-h AUC of 90 mg·h/liter generated by linezolid at 500 mg q12h in 93.8% of human subjects. In conclusion, in our in vitro studies, the QD-administered, pharmacodynamically optimized regimen for linezolid killed drug-susceptible B. anthracis and prevented resistance emergence at lower dosages than q12h regimens. The lower dosage for the pharmacodynamically optimized regimen may decrease drug toxicity. Also, the QD administration schedule may improve patient compliance.

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IN VIVO EVALUATION OF QUINAPRIL TRILAYERED MATRIX TABLETS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2021.v14i7.42002 ◽

2021 ◽

pp. 117-125

Author(s):

ASHWIN K ◽

RAMA MOHAN REDDY T

Keyword(s):

Drug Release ◽

Drug Concentration ◽

In Vitro Release ◽

Matrix Tablets ◽

In Vivo Studies ◽

Matrix Tablet ◽

In Vivo Evaluation ◽

Drug Content

Objective: The aim was to design, formulate, and evaluate the trilayer matrix tablets incorporated with quinapril for extend drug release. Methods: Quinapril trilayer matrix tablets were formulated using design of experiment software wherein initially 27 formulations (QF1-QF27) were designed for active layer from which one best formulation was chosen based on drug content, swelling index and in vitro release studies. The chosen formulation was formulated into extended release trilayed matrix tablet by varying proportions of polymers by direct compression and was evaluated for various physicochemical parameters, drug release. Best formulation was characterized for Fourier transform infrared (FTIR), stability, and pharmacokinetic study. Results: Out of 27 formulations highest drug release was exhibited by QF16 (98.85%) which was formulated into trilayer matrix tablets (AQF16- HQF16). Out of which EQF16 was found to exhibit highest values with 98.42% swelling index, 99.56% drug content, and 99.72% drug release in 24 h. All quinapril trilayer formulations showed zero-order and first-order for marketed product. The optimized formulation EQF16 was found to exhibit no interaction with excipients interpreted by FTIR and no significant changes were observed after loading for stability. In vivo studies conducted using optimized formulation EQF16 attained peak drug concentration (Tmax) of 4.0±0.06 and 1.0±0.03 h for the optimized and commercial formulations, respectively, while mean maximum drug concentration (Cmax) was 302.64±0.07 ng/mL and was significant (p<0.05) as compared to the quinapril marketed product formulation 358.78±0.75 ng/mL. Conclusion: Hence, quinapril was successfully formulated into trilayer matrix tablet and found to be stable.

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Two different approaches for the prediction of In Vivo plasma concentration-time profile from In Vitro release data of once daily formulations of diltiazem hydrochloride

Archives of Pharmacal Research ◽

10.1007/s12272-009-1918-2 ◽

2009 ◽

Vol 32 (9) ◽

pp. 1317-1329 ◽

Cited By ~ 6

Author(s):

Ehab R. Bendas

Keyword(s):

Plasma Concentration ◽

In Vitro Release ◽

Time Profile ◽

Diltiazem Hydrochloride ◽

Once Daily ◽

Concentration Time ◽

Release Data ◽

Vitro Release

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ComparativeIn VitroandIn VivoEfficacies of Human Simulated Doses of Ceftazidime and Ceftazidime-Avibactam against Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00851-12 ◽

2012 ◽

Vol 56 (12) ◽

pp. 6137-6146 ◽

Cited By ~ 71

Author(s):

Jared L. Crandon ◽

Virna J. Schuck ◽

Mary Anne Banevicius ◽

Marie-Eve Beaudoin ◽

Wright W. Nichols ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Hollow Fiber ◽

Time Profile ◽

Fiber System ◽

Content Type ◽

Concentration Time ◽

Infection Models ◽

Immunocompetent Mice

ABSTRACTThe combination of ceftazidime and avibactam possesses potent activity against resistant Gram-negative pathogens, includingPseudomonas aeruginosa. We compared the efficacies of human simulated doses of ceftazidime and ceftazidime-avibactam using a hollow-fiber system and neutropenic and immunocompetent murine thigh infection models. Twenty-seven clinicalP. aeruginosaisolates with ceftazidime MICs of 8 to 128 mg/liter and ceftazidime-avibactam MICs of 4 to 32 mg/liter were utilized in neutropenic mouse studies; 15 of the isolates were also evaluated in immunocompetent mice. Six isolates were studied in both the hollow-fiber system and the neutropenic mouse. In both systems, the free drug concentration-time profile seen in humans given 2 g of ceftazidime every 8 h (2-h infusion), with or without avibactam at 500 mg every 8 h (2-h infusion), was evaluated.In vivoactivity was pharmacodynamically predictable based on the MIC. Ceftazidime decreased bacterial densities by ≥0.5 log unit for 10/27 isolates, while ceftazidime-avibactam did so for 22/27 isolates. In immunocompetent animals, enhancements in activity were seen for both drugs, with ceftazidime achieving reductions of ≥0.3 log unit for 10/15 isolates, whereas ceftazidime-avibactam did so against all 15 isolates.In vitro, ceftazidime resulted in regrowth by 24 h against all isolates, while ceftazidime-avibactam achieved stasis or better against 4/7 isolates. Mutants with elevated ceftazidime-avibactam MICs appeared after 24 h from 3/7 isolates studiedin vitro; however, no resistant mutants were detectedin vivo. Against this highly ceftazidime-nonsusceptible population ofP. aeruginosa, treatment with human simulated doses of ceftazidime-avibactam resulted in pharmacodynamically predictable activity, particularlyin vivo, against isolates with MICs of ≤16 mg/liter, and this represents a potential new option to combat these difficult-to-treat pathogens.

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