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 Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technology

2009 ◽  
Vol 59 (1) ◽  
pp. 15-30 ◽  
Author(s):  
Pramod Kumar ◽  
Sanjay Singh ◽  
Brahmeshwar Mishra
Keyword(s):  
Drug Release ◽  
Extended Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Tramadol Hydrochloride ◽  
Release Formulation ◽  
Extended Release Formulation

Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technologyExtended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media.In vivostudy was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax,tmax,AUC0-24,MRT) and relative bioavailability were calculated. Thein vitroandin vivoresults were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation.In vitro-in vivocorrelation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R= 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.

scholarly journals Physiologically Relevant In Vitro-In Vivo Correlation (IVIVC) Approach for Sildenafil with Site-Dependent Dissolution

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 251 ◽  
Author(s):  
Tae Hwan Kim ◽  
Soyoung Shin ◽  
Seok Won Jeong ◽  
Jong Bong Lee ◽  
Beom Soo Shin
Keyword(s):  
Dissolution Kinetics ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Wet Granulation ◽  
Population Pharmacokinetic ◽  
Beagle Dogs ◽  
Concentration Time ◽  
In Vivo Dissolution

This study aimed to establish a physiologically relevant in vitro-in vivo correlation (IVIVC) model reflecting site-dependent dissolution kinetics for sildenafil based on population-pharmacokinetic (POP-PK) modeling. An immediate release (IR, 20 mg) and three sustained release (SR, 60 mg) sildenafil tablets were prepared by wet granulation method. In vitro dissolutions were determined by the paddle method at pH 1.2, 4.5, and 6.8 media. The in vivo pharmacokinetics were assessed after oral administration of the prepared IR and SR formulations to Beagle dogs (n = 12). The dissolution of sildenafil from SR formulations was incomplete at pH 6.8, which was not observed at pH 1.2 and pH 4.5. The relative bioavailability was reduced with the decrease of the dissolution rate. Moreover, secondary peaks were observed in the plasma concentration-time curves, which may result from site-dependent dissolution. Thus, a POP-PK model was developed to reflect the site-dependent dissolution by separately describing the dissolution and absorption processes, which allowed for estimation of the in vivo dissolution of sildenafil. Finally, an IVIVC was established and validated by correlating the in vitro and in vivo dissolution rates. The present approach may be applied to establish IVIVC for various drugs with complex dissolution kinetics for the development of new formulations.

scholarly journals Gastroretentive Pulsatile Release Tablets of Lercanidipine HCl: Development, Statistical Optimization, andIn VitroandIn VivoEvaluation

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Gagganapalli Santhoshi Reddy ◽  
Usha Yogendra Nayak ◽  
Praful Balavant Deshpande ◽  
Srinivas Mutalik
Keyword(s):  
Blood Pressure ◽  
Drug Release ◽  
Immediate Release ◽  
Lag Time ◽  
Early Morning ◽  
Quadratic Model ◽  
Pharmacokinetic Parameters ◽  
Pulsatile Release

The present study was aimed at the development of gastroretentive floating pulsatile release tablets (FPRTs) of lercanidipine HCl to enhance the bioavailability and treat early morning surge in blood pressure. Immediate release core tablets containing lercanidipine HCl were prepared and optimized core tablets were compression-coated using buoyant layer containing polyethylene oxide (PEO) WSR coagulant, sodium bicarbonate, and directly compressible lactose. FPRTs were evaluated for variousin vitrophysicochemical parameters, drug-excipient compatibility, buoyancy, swelling, and release studies. The optimized FPRTs were testedin vivoin New Zealand white rabbits for buoyancy and pharmacokinetics. DoE optimization of data revealed FPRTs containing PEO (20% w/w) with coat weight 480 mg were promising systems exhibiting good floating behavior and lag time in drug release. Abdominal X-ray imaging of rabbits after oral administration of the tablets, confirmed the floating behavior and lag time. A quadratic model was suggested for release at 7th and 12th h and a linear model was suggested for release lag time. The FPRT formulation improved pharmacokinetic parameters compared to immediate release tablet formulation in terms of extent of absorption in rabbits. As the formulation showed delay in drug release bothin vitroandin vivo, nighttime administration could be beneficial to reduce the cardiovascular complications due to early morning surge in blood pressure.

scholarly journals A Comparison between Use of Spray and Freeze Drying Techniques for Preparation of Solid Self-Microemulsifying Formulation of Valsartan andIn VitroandIn VivoEvaluation

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Sanjay Kumar Singh ◽  
Parameswara Rao Vuddanda ◽  
Sanjay Singh ◽  
Anand Kumar Srivastava
Keyword(s):  
Particle Size ◽  
Freeze Drying ◽  
Tween 80 ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Drying Methods ◽  
Flowing Powder ◽  
Capmul Mcm

The objective of the present study was to develop self micro emulsifying formulation (SMEF) of valsartan to improve its oral bioavailability. The formulations were screened on the basis of solubility, stability, emulsification efficiency, particle size and zeta potential. The optimized liquid SMEF contains valsartan (20% w/w), Capmul MCM C8 (16% w/w), Tween 80 (42.66% w/w) and PEG 400 (21.33% w/w) as drug, oil, surfactant and co-surfactant, respectively. Further, Liquid SMEF was adsorbed on Aerosol 200 by spray and freeze drying methods in the ratio of 2 : 1 and transformed into free flowing powder. Both the optimized liquid and solid SMEF had the particle size <200 nm with rapid reconstitution properties. Both drying methods are equally capable for producing stable solid SMEF and immediate release of drug inin vitroandin vivoconditions. However, the solid SMEF produced by spray drying method showed high flowability and compressibility. The solid state characterization employing the FTIR, DSC and XRD studies indicated insignificant interaction of drug with lipid and adsorbed excipient. The relative bioavailability of solid SMEF was approximately 1.5 to 3.0 folds higher than marketed formulation and pure drug. Thus, the developed solid SMEF illustrates an alternative delivery of valsartan as compared to existing formulations with improved bioavailability.

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 ABSOLUTE AND RELATIVE BIOAVAILABILITY STUDY FOR THE NEWLY DEVELOPED NASAL NANOEMULSION IN SITU GEL OF ONDANSETRON HCl IN COMPARISON TO CONVENTIONALLY PREPARED IN SITU GEL AND INTRAVENOUS DOSAGES FORMS

2018 ◽  
Vol 10 (5) ◽  
pp. 105
Author(s):  
Nidhal K. Maraie ◽  
Yasser Q. Almajidi ◽  
Ahmed Alshadher
Keyword(s):  
Relative Bioavailability ◽  
The Body ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Studies ◽  
Bioavailability Enhancement ◽  
In Situ Gel ◽  
Bioavailability Study ◽  
The Absolute

Objective: The aim of the work was to study the absolute and relative bioavailability (using rabbits) of ondansetron HCl (ONH)from our newly prepared intranasal mucoadhesive nanoemulsion in situ gel (NIG) in comparison to intranasal mucoadhesive in situ gel (IG) prepared by the conventional method and intravenous injection.Methods: Six male rabbits weighing 2.5-3 kg were used in this study, where the dose of ondansetron HCl (ONH) was calculated based on the body surface area (BSA) which is equivalent to 140μl (containing 10 mg/ml) of NIG and IG and 700μl of intravenous Zofran® injection (containing 2 mg/ml) were given to the rabbits, separated with one week washout period. Serial blood samples were withdrawn and analyzed for simultaneous determination of the drug using HPLC (Knaure; 150 ×4.6 mm; 5 μm particle size; 25 cm length) supported by guard column C18-4 mm diameter.Results: The pharmacokinetics parameters for NIG; Cmax, Tmax, AUC0-t, AUC0-∞were found to be greater than conventional in situ gel (IG). In vivo pharmacokinetic studies in rabbits showed a significant increase in Cmax and AUC 0-α(P<0.001) with shorter Tmaxusing NIG compared to IG containing the same NIG excipients, while the absolute bioavailability for NIG and IG (was 80.541 and 51.068 respectively).Conclusion: The present studies ratify the bioavailability enhancement potential of NE used to prepare NIG for the drug and significantly high absolute bioavailability to be used as a successful alternative route to the IV injection and improve patient compliance.

scholarly journals Preparation and in vivo evaluation of a gel-based nasal delivery system for risperidone

2016 ◽  
Vol 66 (4) ◽  
pp. 555-562 ◽  
Author(s):  
Fugen Gu ◽  
Weina Ma ◽  
Gendalai Meng ◽  
Chunzhi Wu ◽  
Yi Wang
Keyword(s):  
Relative Bioavailability ◽  
Nasal Delivery ◽  
Oral Drug ◽  
Pharmacokinetic Parameters ◽  
In Vivo Evaluation ◽  
Fast Absorption ◽  
Maximal Plasma ◽  
Vitro Effect

Abstract The aim of this study was to prepare a nasal gel of risperidone and to investigate the pharmacokinetics and relative bioavailability of the drug in rats. Compared with oral dosing, the risperidone nasal gel exhibited very fast absorption and high bioavailability. Maximal plasma concentration (cmax) and the time to reach cmax (tmax) were 15.2 μg mL-1 and 5 min for the nasal gel, 3.6 μg mL-1 and 30 min for the oral drug suspension, respectively. Pharmacokinetic parameters such as tmax′, cmax and AUC of oral and nasal routes were significantly different (p < 0.01). Relative bioavailability of the drug nasal preparation to the oral suspension was up to 1600.0 %. Further, the in vitro effect of the risperidone nasal gel on nasal mucociliary movement was also investigated using a toad palate model. The risperidone nasal formulation showed mild ciliotoxicity, but the adverse effect was temporary and reversible.

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 Preparation, characterization, and in vivo pharmacokinetics of thermosensitive in situ nasal gel of donepezil hydrochloride

2020 ◽  
Vol 70 (3) ◽  
pp. 411-422 ◽  
Author(s):  
Fugen Gu ◽  
Huimin Fan ◽  
Zhixin Cong ◽  
Shuang Li ◽  
Yi Wang ◽  
...  
Keyword(s):  
Ph Value ◽  
Relative Bioavailability ◽  
Nasal Delivery ◽  
Poloxamer 407 ◽  
Nasal Administration ◽  
Pharmacokinetic Parameters ◽  
Donepezil Hydrochloride

AbstractDonepezil hydrochloride thermosensitive in situ gel for nasal delivery was prepared by using Poloxamer 407 and Poloxamer 188 as thermoreversible polymers, hydroxypropyl-β-cyclodextrin and ethylparaben as permeation enhancer and preservative, respectively. The gelation temperature and time, pH value of the gel formulation were found to meet the requirements for nasal administration. The in vitro erosion and in vitro release tests exhibited obvious drug sustained release behavior. Meantime, main pharmacokinetic parameters such as tmax, cmax and AUC in plasma as well as in brain were significantly different between the nasal gel formulation and intragastric drug solution in rats (p < 0.01). The relative bioavailability and drug targeting efficiency of the gel formulation were calculated to be 385.6 and 151.2 %, respectively. Thus, the drug gel formulation might be a potential new delivery system for treatment of Alzheimer’s disease due to its higher bioavailability and better distribution to brain when compared to oral route.

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