scholarly journals QbD based Eudragit coated Meclizine HCl immediate and extended release multiparticulates: formulation, characterization and pharmacokinetic evaluation using HPLC-Fluorescence detection method

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Faaiza Qazi ◽  
Muhammad Harris Shoaib ◽  
Rabia Ismail Yousuf ◽  
Fahad Siddiqui ◽  
Muhammad Iqbal Nasiri ◽  
...  
Keyword(s):  
Extended Release ◽  
Geometric Mean ◽  
Compartmental Analysis ◽  
Immediate Release ◽  
Drug Analysis ◽  
Fluorescence Method ◽  
Pharmacokinetic Parameters ◽  
Comparative Pharmacokinetic ◽  
Time Period ◽  
Pharmacokinetic Evaluation

Abstract This study is based on the QbD development of extended-release (ER) extruded-spheronized pellets of Meclizine HCl and its comparative pharmacokinetic evaluation with immediate-release (IR) pellets. HPLC-fluorescence method was developed and validated for plasma drug analysis. IR drug cores were prepared from lactose, MCC, and PVP using water as granulating fluid. Three-level, three-factor CCRD was applied for modeling and optimization to study the influence of Eudragit (RL100-RS100), TEC, and talc on drug release and sphericity of coated pellets. HPLC-fluorescence method was sensitive with LLOQ 1 ng/ml and linearity between 10 and 200 ng/ml with R2 > 0.999. Pharmacokinetic parameters were obtained by non-compartmental analysis and results were statistically compared using logarithmically transformed data, where p > 0.05 was considered as non-significant with a 90% CI limit of 0.8–1.25. The AUC0–t and AUC0–∞ of ER pellets were not significantly different with geometric mean ratio 1.0096 and 1.0093, respectively. The Cmax of IR pellets (98.051 ng/ml) was higher than the ER pellets (84.052 ng/ml) and the Tmax of ER pellets (5.116 h) was higher than the IR pellets (3.029 h). No significant food effect was observed on key pharmacokinetic parameters of ER pellets. Eudragit RL100 (6%) coated Meclizine HCl pellets have a potential therapeutic effect for an extended time period.

scholarly journals Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

2016 ◽  
Vol 60 (4) ◽  
pp. 2492-2498 ◽  
Author(s):  
Marcelo Gomes Davanço ◽  
Michel Leandro Campos ◽  
Talita Atanazio Rosa ◽  
Elias Carvalho Padilha ◽  
Alejandro Henao Alzate ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Extended Release ◽  
Hydroxypropyl Methylcellulose ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Success ◽  
Preclinical Pharmacokinetics ◽  
Bioavailability Study

ABSTRACTBenznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.

scholarly journals Bioequivalence of Two Oral Formulations of Ciprofloxacin 250 mg Tablets in Healthy Mexican Volunteers

2019 ◽  
Vol 1 (1) ◽  
pp. 104-109
Author(s):  
Suset J. Tolentino-Hernández ◽  
Leticia Cruz-Antonio ◽  
Irma Torres-Roque ◽  
Jose T. Pérez-Urizar
Keyword(s):  
Confidence Intervals ◽  
Plasma Concentrations ◽  
Compartmental Analysis ◽  
Immediate Release ◽  
Hplc Method ◽  
Pharmacokinetic Parameters ◽  
Test Results ◽  
Oral Formulations ◽  
Acceptance Range ◽  
Bioequivalence Test

Background. There are numerous reports of low-quality formulations of ciprofloxacin in the market, which has been associated with therapeutic failure and the development of microbial resistance. Objective. The aim of this study is evaluating the bioequivalence between two oral immediate-release ciprofloxacin 250 mg tablets. Material and Methods. The study was performed in 24 Mexican healthy volunteers following a randomized cross over 2 × 2 design. Single doses of a test formulation Lemyflox® (Lemery Laboratories, Mexico) and the reference formulation Ciproxina® (Bayer, Mexico) were administered; blood samples were obtained during a 12 h period. Ciprofloxacin plasma concentrations were quantified using a validated High-Pressure Liquid Chromatography (HPLC) method, plasma concentration against time curves were constructed and pharmacokinetic parameters were determined by non-compartmental analysis. In order to determine bioequivalence, test/reference ratios of Cmax, AUC0-t and AUC0-inf were compared using analysis of variance (ANOVA), followed by the 90 % confidence intervals and the Schuirmann bilateral test. Results. The 90 % confidence intervals limits ranged from 82.92 to 100.88 % for Cmax, from 93.05 to 109.15 % for AUC0-t and from 97.76 to 114.99 % for AUC0-inf, all cases were within bioequivalence acceptance range of 80 - 125 %. Schuirmann test confirmed such observation as the probability that Cmax, AUC0-t and AUC0-inf ratios were beyond 80 - 125 % was lower than 0.05. Conclusions. The results obtained demonstrate bioequivalence between the test and reference formulations.

scholarly journals Novel Pharmacokinetic-Pharmacodynamic Model for Prediction of Outcomes with an Extended-Release Formulation of Ciprofloxacin

2004 ◽  
Vol 48 (6) ◽  
pp. 2061-2068 ◽  
Author(s):  
Alison K. Meagher ◽  
Alan Forrest ◽  
Axel Dalhoff ◽  
Heino Stass ◽  
Jerome J. Schentag
Keyword(s):  
Mathematical Model ◽  
Time Course ◽  
Extended Release ◽  
Geometric Mean ◽  
Bacterial Load ◽  
Pharmacodynamic Model ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Bacterial Killing ◽  
Significant Difference

ABSTRACT The pharmacokinetics of an extended-release (XR) formulation of ciprofloxacin has been compared to that of the immediate-release (IR) product in healthy volunteers. The only significant difference in pharmacokinetic parameters between the two formulations was seen in the rate constant of absorption, which was approximately 50% greater with the IR formulation. The geometric mean plasma ciprofloxacin concentrations were applied to an in vitro pharmacokinetic-pharmacodynamic model exposing three different clinical strains of Escherichia coli (MICs, 0.03, 0.5, and 2.0 mg/liter) to 24 h of simulated concentrations in plasma. A novel mathematical model was derived to describe the time course of bacterial CFU, including capacity-limited replication and first-order rate of bacterial clearance, and to model the effects of ciprofloxacin concentrations on these processes. A “mixture model” was employed which allowed as many as three bacterial subpopulations to describe the total bacterial load at any moment. Comparing the two formulations at equivalent daily doses, the rates and extents of bacterial killing were similar with the IR and XR formulations at MICs of 0.03 and 2.0 mg/liter. At an MIC of 0.5 mg/liter, however, the 1,000-mg/day XR formulation showed a moderate advantage in antibacterial effect: the area under the CFU-time curve was 45% higher for the IR regimen; the nadir log CFU and 24-h log CFU values for the IR regimen were 3.75 and 2.49, respectively; and those for XR were 4.54 and 3.13, respectively. The mathematical model explained the differences in bacterial killing rate for two regimens with identical AUC/MIC ratios.

A pharmacokinetic evaluation of single and multiple doses of extended-release hydrocodone bitartrate in subjects experiencing surgical or osteoarthritic pain

2015 ◽  
Vol 11 (5) ◽  
pp. 405 ◽  
Author(s):  
Cynthia Y. Robinson, PhD ◽  
Christopher M. Rubino, PharmD ◽  
Stephen J. Farr, PhD
Keyword(s):  
Single Dose ◽  
Steady State ◽  
Extended Release ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Immediate Release ◽  
Pharmacokinetic Parameters ◽  
Single Dose Study ◽  
Dosing Interval ◽  
Osteoarthritic Pain

Objectives: To assess the single-dose and steady-state pharmacokinetics of a single-entity hydrocodone extended-release (ER) formulation in patients enrolled in two separate phase 2 clinical studies.Setting: Both studies were multicenter clinical studies.Subjects and interventions: In study 1, 115 subjects with postsurgical pain (bunionectomy) received single doses of 10, 20, 30, or 40 mg hydrocodone-ER, 10 mg hydrocodone/325 mg acetaminophen immediate-release (IR), or placebo. In study 2, 37 subjects with osteoarthritic pain received doses of 10, 20, 30, or 40 mg of hydrocodone-ER twice-daily for 7 days. Venous blood samples were taken periodically up to 24 hours postdosing after the single dose (study 1) or after 7 days of dosing (study 2) and were assayed for concentrations of hydrocodone and its major metabolites.Main outcome measures: Standard pharmacokinetic parameters were estimated by noncompartmental analysis methods.Results: Following a single dose of hydrocodone-ER, Tmax was prolonged to approximately 6 hours at all dose levels of hydrocodone-ER compared with 2.9 hours for the IR formulation. All doses of hydrocodone-ER formulations provided prolonged and sustained release of hydrocodone throughout the 12-hour dosing interval with reduced peak-to-trough fluctuation at steady state compared with hydrocodone/acetaminophen-IR comparator. Both single-dose and steady-state mean Cmax and AUClast values showed reasonable dose-proportionality. Norhydrocodone and hydromorphone plasma concentrations were 32-38 percent and <2.1 percent, respectively, of hydrocodone concentrations in both studies.Conclusions: The sustained plasma concentrations of hydrocodone support twice-daily dosing with a 12-hour dosing interval.

scholarly journals Comparison of Azithromycin Pharmacokinetics following Single Oral Doses of Extended-Release and Immediate-Release Formulations in Children with Acute Otitis Media

2011 ◽  
Vol 55 (11) ◽  
pp. 5022-5026 ◽  
Author(s):  
Ping Liu ◽  
Annie F. Fang ◽  
Robert R. LaBadie ◽  
Penelope H. Crownover ◽  
Adriano G. Arguedas
Keyword(s):  
Single Dose ◽  
Otitis Media ◽  
Extended Release ◽  
Geometric Mean ◽  
Acute Otitis Media ◽  
Lower Boundary ◽  
Systemic Exposure ◽  
Immediate Release ◽  
Oral Suspension ◽  
Tolerability Profile

ABSTRACTAn azithromycin extended-release (ER) oral suspension was developed to improve the gastrointestinal tolerability profile without substantially compromising systemic exposure. A single dose of 30 mg/kg azithromycin immediate-release (IR) oral suspension has been used in children to treat acute otitis media (AOM). This study was conducted to compare the pharmacokinetics of a 60-mg/kg azithromycin ER single dose with a 30-mg/kg azithromycin IR single dose in children with AOM aged 6 months to 6 years (n= 19 per treatment). Serum samples were collected at 1, 2, 3, 4, 8, 24, 48, and 72 h after dosing. The area under the curve from time zero to 72 h postdosing (AUC0-72) was calculated based on a noncompartmental method. One-way analysis of variance (ANOVA) was used to compare exposure parameters (e.g., AUC0-72and peak concentration) as well as concentrations at each time point. The adjusted geometric mean ratio of the ER/IR AUC0-72was 157.98% (90% confidence interval [CI], 98.87%, 252.44%), which met the predefined criterion of the lower boundary of the 90% CI of ≥80%. As expected, due to the slower-release profile of the ER formulation, the concentrations of the ER formulation during the first 3 h were lower than those of the IR formulation. After 3 h postdosing, the lower boundaries of the 90% CI for the ER/IR concentration ratios were greater than 100%. These results indicated that a 60-mg/kg single dose of ER azithromycin provides similar or greater systemic exposure in children than the 30-mg/kg single dose of IR azithromycin.

Comparative steady-state pharmacokinetic evaluation of immediate-release topiramate and USL255, a once-daily extended-release topiramate formulation

Epilepsia ◽  
2013 ◽  
Vol 54 (8) ◽  
pp. 1444-1452 ◽  
Author(s):  
Meir Bialer ◽  
Tawfeeq Shekh-Ahmad ◽  
Tricia L. Braun ◽  
Mark B. Halvorsen
Keyword(s):  
Steady State ◽  
Extended Release ◽  
Immediate Release ◽  
Once Daily ◽  
Pharmacokinetic Evaluation

scholarly journals Pharmacokinetic Evaluation of Twice-Daily Extended-Release Carbamazepine (CBZ) and Four-Times-Daily Immediate-Release CBZ in Patients with Epilepsy

Epilepsia ◽  
1998 ◽  
Vol 39 (3) ◽  
pp. 274-279 ◽  
Author(s):  
William R. Garnett ◽  
Benjamin Levy ◽  
Angus M. McLean ◽  
Yuxin Zhang ◽  
Richard A. Couch ◽  
...  
Keyword(s):  
Extended Release ◽  
Immediate Release ◽  
Patients With Epilepsy ◽  
Pharmacokinetic Evaluation

scholarly journals Miconazole Oral Gel Increases Exposure to Oral Oxycodone by Inhibition of CYP2D6 and CYP3A4

2010 ◽  
Vol 55 (3) ◽  
pp. 1063-1067 ◽  
Author(s):  
Juha Grönlund ◽  
Teijo I. Saari ◽  
Nora Hagelberg ◽  
Pertti J. Neuvonen ◽  
Klaus T. Olkkola ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Plasma Concentrations ◽  
Immediate Release ◽  
Inhibitory Effect ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Oxidative Metabolites ◽  
Gel Treatment ◽  
Strong Inhibitory Effect ◽  
Two Phases

ABSTRACTOur aim was to assess the effect of miconazole oral gel on the pharmacokinetics of oral oxycodone. In an open crossover study with two phases, 12 healthy volunteers took a single oral dose of 10 mg of immediate-release oxycodone with or without thrice-daily 85-mg miconazole oral gel treatment. The plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 h. Pharmacological effects of oxycodone were recorded for 12 h. Pharmacokinetic parameters were compared by use of the geometric mean ratios (GMRs) and their 90% confidence interval (CIs). Pretreatment with miconazole oral gel caused a strong inhibition of the CYP2D6-dependent metabolism and moderate inhibition of the CYP3A4-dependent metabolism of oxycodone. The mean area under the concentration-time curve (AUC) from time zero to infinity (AUC0-∞; GMR, 1.63; 90% CI, 1.48 to 1.79) and the peak concentration of oxycodone (GMR, 1.31; 90% CI, 1.19 to 1.44) were increased. The AUC of the CYP2D6-dependent metabolite oxymorphone was greatly decreased (GMR, 0.17; 90% CI, 0.09 to 0.31) by miconazole gel, whereas that of the CYP3A4-dependent metabolite noroxycodone was increased (GMR, 1.30; 90% CI, 1.15 to 1.47) by miconazole gel. Differences in the pharmacological response to oxycodone between phases were insignificant. Miconazole oral gel increases the exposure to oral oxycodone, but the clinical relevance of the interaction is moderate. Miconazole oral gel produces a rather strong inhibitory effect on CYP2D6, which deserves further study.

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