scholarly journals Development of Paroxetine Hydrochloride Single Layer Controlled-Release Tablets Based on 32 Factorial Design

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 243 ◽  
Author(s):  
Yao Yang ◽  
Zhengwei Huang ◽  
Xuan Zhang ◽  
Jinyuan Li ◽  
Ying Huang ◽  
...  
Keyword(s):  
Controlled Release ◽  
Single Layer ◽  
Suicide Mortality ◽  
Pharmacokinetic Parameters ◽  
Release Mechanism ◽  
Time Curve ◽  
Layer Separation ◽  
Significant Difference ◽  
Paroxetine Hydrochloride ◽  
Controlled Release Tablets

Major depressive disorder (MDD) is one of the main contributors to disability and suicide mortality globally. Paroxetine hydrochloride (PHH) is the most potent antidepressant used for MDD treatment. Due to its reduced side effects PAXIL® CR is a widely-used controlled-release formulation of PHH. However, the complicated double-layer production of PAXIL® CR faces the risk of layer separation. In this study, PHH enteric coating single layer controlled-release tablets (PHH-EC-SLTs) were designed as a simplified substitution of PAXIL® CR through a rational formulation screening. The optimized PHH-EC-SLTs showed similar release behaviors in vitro to PAXIL® CR and the release profiles corresponded to a zero-order release model (R2 = 0.9958). Polymer matrix erosion was the main release mechanism, according to the fitting exponents n > 1 in the Korsmeyer-Pappas model. Crucial pharmacokinetic parameters including peak-reaching time (Tmax), peak concentration (Cmax) and the area under the blood level-time curve (AUC0-48) of PHH-EC-SLTs and PAXIL® CR had no significant difference (p > 0.05) and the relative bioavailability (F = 97.97%) of PHH-EC-SLTs demonstrated their similar pharmacokinetic profiles in vivo. In view of avoiding layer separation risk and simplifying the preparation processing, the self-made PHH-EC-SLTs could be considered as a safe and economic alternative to PAXIL® CR.

scholarly journals Pharmacokinetics of intramuscularly administered aminosidine in healthy subjects.

1997 ◽  
Vol 41 (5) ◽  
pp. 982-986 ◽  
Author(s):  
T P Kanyok ◽  
A D Killian ◽  
K A Rodvold ◽  
L H Danziger
Keyword(s):  
Healthy Subjects ◽  
Randomized Clinical Trials ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Multiple Drug ◽  
Time Data ◽  
Time Curve ◽  
First Order ◽  
Significant Difference

Aminosidine is an older, broad-spectrum aminoglycoside antibiotic that has been shown to be effective in in vitro and animal models against multiple-drug-resistant tuberculosis and the Mycobacterium avium complex. The objective of this randomized, parallel trial was to characterize the single-dose pharmacokinetics of aminosidine sulfate in healthy subjects (eight males, eight females). Sixteen adults (mean [+/- standard deviation] age, 27.6 +/- 5.6 years) were randomly allocated to receive a single, intramuscular aminosidine sulfate injection at a dose of 12 or 15 mg/kg of body weight. Serial plasma and urine samples were collected over a 24-h period and used to determine aminosidine concentrations by high-performance liquid chromatographic assay. A one-compartment model with first-order input, first-order output, and a lag time (Tlag) and with a weighting factor of 1/y2 best described the data. Compartmental and noncompartmental pharmacokinetic parameters were estimated with the microcomputer program WinNonlin. One subject was not included (15-mg/kg group) because of the lack of sampling time data. On average, subjects attained peak concentrations of 22.4 +/- 3.2 microg/ml at 1.34 +/- 0.45 h. All subjects had plasma aminosidine concentrations below 2 microg/ml at 12 h, and all but two subjects (one in each dosing group) had undetectable plasma aminosidine concentrations at 24 h. The dose-adjusted area under the concentration-time curve from 0 h to infinity of aminosidine was identical for the 12- and 15-mg/kg groups (9.29 +/- 1.5 versus 9.29 +/- 2.2 microg x h/ml per mg/kg; P = 0.998). Similarly, no significant differences (P > 0.05) were observed between dosing groups for peak aminosidine concentration in plasma, time to peak aminosidine concentration in plasma, Tlag, apparent clearance, renal clearance, elimination rate constant, and elimination half-life. A significant difference was observed for the volume of distribution (0.35 versus 0.41 liters/kg; P = 0.037) between the 12 and 15 mg/kg dosing groups. Now that comparable pharmacokinetic profiles between dosing groups have been demonstrated, therapeutic equivalency testing via in vitro pharmacokinetic and pharmacodynamic modelling and randomized clinical trials in humans should be conducted.

Synthesis and Evaluation of Starch – Urea – Borate as Rate Controlling Matrix for Controlled Release

1970 ◽  
Vol 1 (2) ◽  
pp. 167-170
Author(s):  
Chowdary KPR ◽  
Murali Krishna MN
Keyword(s):  
Controlled Release ◽  
Release Rate ◽  
Guar Gum ◽  
Matrix Tablets ◽  
Fickian Diffusion ◽  
Release Mechanism ◽  
Drug Release Mechanism ◽  
Zero Order Kinetics ◽  
Diffusion Controlled ◽  
Controlled Release Tablets

The objective of the present investigation is to synthesize starch – urea – borate, a new starch based polymer and to evaluate its application in the design of controlled release matrix tablets of diclofenac and gliclazide. The release rate controlling efficiency of starch – urea – borate was also compared with that of known polymers. Starch – urea – borate (SUB) polymer was synthesized by gelatinization of starch in the presence of urea and borax. Matrix tablets of diclofenac (100 mg) and gliclazide (60 mg) were formulated employing starch – urea – borate polymer in different proportions of drug and polymer and the tablets were evaluated. With both diclofenac and gliclazide, release from the formulated matrix tablets was slow and spread over 24 h and depended on percent polymer in the tablet. Release was diffusion controlled and followed zero order kinetics. Non – fickian diffusion was the drug release mechanism from the formulated tablets. Diclofenac release from matrix tablets formulated employing 33 % SUB (DF3) and Gliclazide release from matrix tablets formulated employing 50 % SUB (GF4) was similar to that from the corresponding commercial SR tablets. Starch – urea – borate polymer was found suitable for the design of oral controlled release tablets of diclofenac and gliclazide. The order of increasing release rate controlling efficiency with various polymers was ethyl cellulose = guar gum > SUB > sodium CMC > HPMC. Starch – urea – borate is a better release rate controlling polymer than HPMC and sodium CMC for obtaining controlled release over    24 hours.

scholarly journals Preparation andIn Vitro/In VivoEvaluation of Vinpocetine Elementary Osmotic Pump System

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Meiying Ning ◽  
Yue Zhou ◽  
Guojun Chen ◽  
Xingguo Mei
Keyword(s):  
Citric Acid ◽  
Controlled Release ◽  
Elimination Rate ◽  
Immediate Release ◽  
Osmotic Pump ◽  
Prolonged Release ◽  
Time Curve ◽  
Release Formulation ◽  
Pump System ◽  
Controlled Release Tablets

Preparation andin vitroandin vivoevaluation of vinpocetine (VIN) elementary osmotic pump (EOP) formulations were investigated. A method for the preparation of VIN elementary osmotic pump tablet was obtained by adding organic acid additives to increase VIN solubility. VIN was used as the active pharmaceutical ingredient, lactose and mannitol as osmotic agent. Citric acid was used as increasing API solubility and without resulting in the API degradation. It is found that the VIN release rate was increasing with the citric acid amount at a constant range. Cellulose acetate 398-3 was employed as semipermeable membrane containing polyethylene glycol 6000 and diethyl-o-phthalate as pore-forming agent and plasticizer for controlling membrane permeability. In addition, a clear difference between the pharmacokinetic patterns of VIN immediate release and VIN elementary osmotic pump formulations was revealed. The area under the plasma concentration-time curve after oral administration of elementary osmotic pump formulations was equivalent to VIN immediate release formulation. Furthermore, significant differences found for mean residence time, elimination half-life, and elimination rate constant values corroborated prolonged release of VIN from elementary osmotic pump formulations. These results suggest that the VIN osmotic pump controlled release tablets have marked controlled release characters and the VIN osmotic pump controlled release tablets and the normal tablets were bioequivalent.

scholarly journals ALTERATION OF PHARMACOKINETIC PARAMETERS OF PENTOXIFYLLINE USING NATURAL MUCOADHESIVE POLYMERS

2019 ◽  
pp. 153-157
Author(s):  
GNANASEKARAN JOHN SELVARAJ ◽  
ARUL BALASUBRAMANIAN ◽  
KOTHAI RAMALINGAM
Keyword(s):  
Drug Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Fold Increase ◽  
Ocimum Basilicum ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Plasma Drug ◽  
Time Curve ◽  
Significant Difference

Objective: The present study was aimed to alter the pharmacokinetic parameters of the drug pentoxifylline using a novel natural mucoadhesive polymer from two different plants, Manilkara zapotta Linn and Ocimum basilicum Linn. Methods: The polymer was isolated and six batches of mucoadhesive tablets of pentoxifylline was formulated with 3 different concentrations of each polymer. The best formulation from each of the polymer was selected and administered to rabbits and the plasma drug concentration was compared with the marketed formulation. The pharmacokinetic parameters such as such as Cmax, tmax, AUC, AUMC, λz, t1/2, and MRT were determined. Results: The plasma drug concentration vs time curve shows the extended-release of pentoxifylline when compared with the conventional marketed formulation. The results show that there is no change in the peak plasma concentration, but the significant difference was observed in t½, which showed approximately 2.5 fold increase from 2.44 to 6.87 h and the AUC showed five-fold increase from 22.40 to 117.19 μg*h/ml, and other pharmacokinetic parameters, when compared with the marketed formulation. Conclusion: The isolated polymer from the plants Manilkara zapotta Linn. and Ocimum basilicum Linn can be used as a carrier for developing mucoadhesive formulations and it alter the pharmacokinetic of pentoxifylline positively.

scholarly journals Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1666
Author(s):  
Ying Li ◽  
Yin Wu ◽  
Ya-Jing Li ◽  
Lu Meng ◽  
Cong-Yang Ding ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Compartmental Model ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Simultaneous Quantification ◽  
Concentration Time ◽  
Significant Difference ◽  
In Vivo Pharmacokinetics

Herein, the effect of silymarin pretreatment on the pharmacokinetics of simvastatin in rats was evaluated. To ensure the accuracy of the results, a rapid and sensitive UPLC–MS/MS method was established for simultaneous quantification of simvastatin (SV) and its active metabolite simvastatin acid (SVA). This method was applied for studying the pharmacokinetic interactions in rats after oral co-administration of silymarin (45 mg/kg) and different concentrations of SV. The major pharmacokinetic parameters, including Cmax, tmax, t1/2, mean residence time (MRT), elimination rate constant (λz) and area under the concentration-time curve (AUC0–12h), were calculated using the non-compartmental model. The results showed that the co-administration of silymarin and SV significantly increased the Cmax and AUC0–12h of SVA compared with SV alone, while there was no significant difference with regards to Tmax and t1/2. However, SV pharmacokinetic parameters were not significantly affected by silymarin pretreatment. Therefore, these changes indicated that drug-drug interactions may occur after co-administration of silymarin and SV.

scholarly journals Pharmacokinetics of Florfenicol in Healthy Pigs and in Pigs Experimentally Infected with Actinobacillus pleuropneumoniae

2003 ◽  
Vol 47 (2) ◽  
pp. 820-823 ◽  
Author(s):  
Jianzhong Liu ◽  
Ki-Fai Fung ◽  
Zhangliu Chen ◽  
Zhenling Zeng ◽  
Jie Zhang
Keyword(s):  
Half Life ◽  
Clinical Signs ◽  
Actinobacillus Pleuropneumoniae ◽  
Pharmacokinetic Parameters ◽  
X Rays ◽  
Time Data ◽  
Time Curve ◽  
Chromatography Method ◽  
Concentration Time ◽  
Significant Difference

ABSTRACT A comparative in vivo pharmacokinetic study of florfenicol was conducted in 18 crossbred pigs infected with Actinobacillus pleuropneumoniae following intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration of a single dose of 20 mg/kg. The disease model was confirmed by clinical signs, X rays, pathohistologic examinations, and organism isolation. Florfenicol concentrations in plasma were determined by a validated high-performance liquid chromatography method with UV detection at a wavelength of 223 nm. Pharmacokinetic parameters were calculated by using the MCPKP software (Research Institute of Traditional Chinese Veterinary Medicine, Lanzhou, China). The disposition of florfenicol after a single i.v. bolus was described by a two-compartment model with values for the half-life at α phase (t 1/2α), the half-life at β phase (t 1/2β), the area under the concentration-time curve (AUC0-∞), and the volume of distribution at steady state (V ss) of 0.37 h, 2.91 h, 64.86 μg · h/ml, and 1.2 liter/kg, respectively. The concentration-time data fitted the one-compartment (after i.m.) and two-compartment (after p.o.) models with first-order absorption. The values for the maximum concentration of drug in serum (C max), t 1/2α, t 1/2β, and bioavailability after i.m. and p.o. dosing were 4.00 and 8.11 μg/ml, 0.12 and 3.91 h, 13.88 and 16.53 h, and 122.7 and 112.9%, respectively, for the two models. The study showed that florfenicol was absorbed quickly and completely, distributed widely, and eliminated slowly in the infected pigs, and there was no statistically significant difference between the pharmacokinetic profiles for the infected and healthy pigs.

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.

scholarly journals ANALYTICAL METHOD VALIDATION, PHARMACOKINETICS AND BIOEQUIVALENCE STUDY OF DIMETHYL FUMARATE IN HEALTHY IRANIAN VOLUNTEERS

2021 ◽  
pp. 6-10
Author(s):  
GHASEMIAN ELHAM ◽  
SADRAI SIMA ◽  
SHOKRI JAVAD ◽  
SAYADI SHAHRAM
Keyword(s):  
Analytical Method ◽  
Reference Product ◽  
Bioequivalence Study ◽  
Dimethyl Fumarate ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Analytical Method Validation ◽  
Significant Difference ◽  
High Concentrations ◽  
Monomethyl Fumarate

Objective: Pharmacokinetic evaluation of Dimethyl Fumarate (DMF) in the Iranian population wasn’t studied. So, the aim of this research is the validation of the analytical method and evaluation of the pharmacokinetic properties and bioequivalence of the generic form of this drug versus the reference product. Methods: 2 single-dose, test, and reference DMF products were orally administered to 24 healthy volunteers. The washout period was 28 d between the treatments. Monomethyl fumarate as the metabolite of DMF was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the method was validated. Also, the pharmacokinetic parameters were calculated for bioequivalence evaluation. Results: The analytical method was validated and linear over the range of 31.25-4000 ng/ml (R2= 0.997). In addition, the method was precise and accurate in the low, medium, and high concentrations. The results indicated that the 2 products had similar pharmacokinetics. Further, the 90% CI of the mean ratios of the test versus the reference products of the log-transformed area under the concentration-time curve over 10 h (0.99 to 1.02) and peak concentration (0.98 to 1.03) were within the acceptable range of 0.8 to 1.25 and the generic product of DMF could be similar to that of the reference product. Conclusion: The applied analytical method is selective, accurate, precise, and repeatable for the analysis of monomethyl fumarate (MMF) in plasma. Also, the bioequivalence study showed no significant difference between the pharmacokinetic parameters of these 2 products. So, the DMF test product can be claimed to be bioequivalent with the reference product.

scholarly journals Pharmacokinetics of Azithromycin Administered Alone and with Atovaquone in Human Immunodeficiency Virus-Infected Children

1999 ◽  
Vol 43 (6) ◽  
pp. 1516-1519 ◽  
Author(s):  
Leock Y. Ngo ◽  
Ram Yogev ◽  
Wayne M. Dankner ◽  
Walter T. Hughes ◽  
Sandra Burchett ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time ◽  
Significant Difference ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
Clinically Significant ◽  
To Receive

ABSTRACT To evaluate if atovaquone (ATQ) interacts pharmacokinetically with azithromycin (AZ) in human immunodeficiency virus-infected children, 10 subjects (ages, 4 to 13 years) were randomized in a crossover study to receive AZ (5 mg/kg/day) alone (ALONE) or AZ (5 mg/kg/day) and ATQ (30 mg/kg/day) simultaneously (SIM) prior to receiving AZ and ATQ staggered by 12 h. Despite a lack of significant difference in the mean AZ pharmacokinetic parameters, the steady-state values of AZ’s area under the concentration-time curve from 0 to 24 h and maximum concentration in serum were consistently lower (n = 7 of 7) for the SIM regimen than they were for the ALONE regimen. A larger study will be required to determine if ATQ affects AZ pharmacokinetics and efficacy in a clinically significant manner.

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