scholarly journals Formulation and Evaluation of Valsartan Solid Lipid Nanoparticles

2021 ◽  
Vol 11 (2-S) ◽  
pp. 103-108
Author(s):  
M. Chandana ◽  
M. Venkata Ramana ◽  
N. Rama Rao
Keyword(s):  
Sustained Release ◽  
Chemical Interaction ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Entrapment Efficiency ◽  
Homogenization Method ◽  
Burst Release ◽  
Angiotensin Ii Antagonist ◽  
Release Curve ◽  
Nano Formulation

Valsartan is a potent and specific competitive angiotensin II antagonist which is used in the management of hypertension. It is well absorbed following oral administration, with rather poor bioavailability of about 25 %. Peak plasma concentration of valsartan occurs 2-4 hours after ingestion. Optimized VAL_SLNS are prepared by hot homogenization method and spray dried to improve handling processing and stability. Solid state studies such as FTIR indicated absence of any chemical interaction between valsartan and the lipid. The mean particles size, Polydispersity index (PDI) and entrapment efficiency of optimized formulation (F-05) was found to be 136.5 nm, 0.424, 80.98% respectively. The drug release study from the nano formulation was studied in Phosphate buffer 6.8 for all the formulations F1 F2 F3 F4 and F5. The results demonstrated that V-SLN formulation (F-5) showed biphasic behaviour with an initial burst release followed by a sustained release maximum up to 72-79% till 12 hours. The release curve was found to follow Korsmeyer Peppas model (R2=0.98). Keywords: hot homogenization, hydrogenated soya phosphatidyl choline, sustained release

Application of Statistical Tooling Techniques for Designing of Carvedilol Nanolipid Transferosomes and its Dermatopharmacokinetic and Pharmacodynamic Studies

2020 ◽  
Vol 8 (6) ◽  
pp. 452-470
Author(s):  
Brito R. Selvaraj ◽  
Seshaiah K. Sridhar ◽  
Bhaskar R. Kesavan ◽  
Sucharitha Palagati
Keyword(s):  
Particle Size ◽  
Plasma Concentration ◽  
Dosage Form ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Entrapment Efficiency ◽  
Transdermal Patch ◽  
In Vitro Drug Release

Background: The hypothesis is to augment the bioavailability and therapeutic potential of low bioavailable Carvedilol (25-35%) through Nanostructured Lipid Carrier (NLC) loaded Transdermal patch (Nanolipid Transferosomes). Methods: Box-Behnken design was designed to formulate NLC through a hot homogenization technique. About 17 formulations (C1-C17) were formulated by varying the critical material attribute and critical process parameter. Optimization was done based on its critical quality attributes like particle size, zeta potential and entrapment efficiency. Selected NLC (C16) has been fabricated into a transdermal patch through solvent evaporation technique and estimated for thickness, weight variation, moisture content, folding endurance, drug content, in vitro drug release, ex vivo skin permeation studies 48 hrs, in vitro drug release kinetic studies and skin irritation studies. In vivo pharmacokinetics and pharmacodynamic study parameters were compared between carvedilol loaded NLC transdermal patch and a conventional formulation (Coreg CR). Results: NLC (C16) was selected as the best formulation based on desirable, less particle size (201.1 ± 2.02 nm), more zeta potential (-37.2 ± 1.84mV) and maximum entrapment efficiency (87.54 ± 1.84%). Experimental investigations of in vivo dermatopharmacokinetic data shown statistically significant changes (p<0.05) in the parameter (increased AUC0-α, MRT with decreased Cmax, Tmax) when administered through the transdermal patch and on compared to the conventional dosage form. It was observed that there was a significant change with p<0.05 among the pharmacokinetic factors of conventional Carvedilol formulation, Carvedilol NLC and Carvedilol NLC loaded Transdermal patch with a maximum time of peak plasma concentration (Tmax) of 4 hrs, 8 hrs and 8 hrs; maximum peak plasma concentration (Cmax) of 0.258 μg/ml, 0.208 μg/ml and 0.108 μg/ml. Area Under Curve (AUC0-α) was established to be 125.127 μg/ml/h, 132.576 μg/ml.h and 841.032 μg/ml.h. Mean Residence Time (MRT0- α) of the drug was established to be 17 hrs, 19 hrs and 82 hrs, respectively. This data reveals the impact of NLC on the enhancement of bioavailability through a transdermal patch. In vivo pharmacodynamic studies confirm that NLC loaded transdermal patch (Nanolipid Transferosomes) shows a significant control in blood pressure for 48 hrs when compared to the conventional dosage form. Conclusion: This research data concludes that NLC loaded transdermal patch (Nanolipid Transferosomes) was a suitable candidate to enhance the bioavailability of low bioavailable drug-like Carvedilol. Lay Summary: It was inferred from the literature that NLC filled transdermal patches were a novel strategy to increase the solubility and permeability of Carvedilol, which has less bioavailability. It reveals that there was no reproducible preparation for the NLC. It also reveals that the option of formulation and process parameters for the formation of NLC is not clearly justified. On account of this, an uniquely validated and optimized formulation technique was developed for NLC with low soluble and poorly bioavailable carvedilol, tested in Albino wistar rats for enhancement of bioavailability, the same study has been performed and proved.

Comparative Bioequivalence and Efficacy of Two Sustained-Release Procainamide Formulations in Patients with Cardiac Arrhythmias

1988 ◽  
Vol 22 (7-8) ◽  
pp. 554-558 ◽  
Author(s):  
Daniel E. Hilleman ◽  
Albert J. Patterson ◽  
Syed M. Mohiuddin ◽  
Brian G. Ortmeier ◽  
Christopher J. Destache
Keyword(s):  
Plasma Concentration ◽  
Sustained Release ◽  
Cardiac Arrhythmias ◽  
Peak Plasma ◽  
Statistical Significance ◽  
Peak Plasma Concentration ◽  
Plasma Concentrations ◽  
Blood Sampling ◽  
Time Curve ◽  
Alternate Test

This investigation evaluated the bioequivalence and efficacy of two sustained-release procainamide products. Ten patients with cardiac arrhythmias were randomized to product A (Procan-SR) or product B (Pronestyl-SR). After nine doses of study medication, plasma procainamide and N-acetylprocainamide concentrations were obtained to determine the area under the concentration versus time curve at steady state (AUCss), mean plasma concentration (Cavss), the observed peak plasma concentration (Cmaxss), the observed trough plasma concentration (Cminss), and the apparent time to achieve Cmaxss (tmax). The products were compared on a milligram-equivalent (adjusted) basis. Following completion of blood sampling, patients were crossed-over to the alternate product. There was no washout between treatments. After nine doses of the alternate test medications, blood sampling was repeated. Differences in AUCss, Cavss, Cmaxss, tmax, and intradose peak/trough ratios were not statistically significant. Within-group variability in AUCss, Cavss Cmaxss, and tmax was greater with product B, but this trend did not reach statistical significance. Antiarrhythmic efficacy was not significantly different between the two treatments. Although the greater bioequivalence, lesser variability, and the greater number of tablet dosage sizes would favor product A, patients stabilized on a particular brand of sustained-release procainamide should not be switched to another product without careful monitoring. One patient in this study developed nonsustained ventricular tachycardia with low procainamide plasma concentrations after being switched from product A to product B.

Pharmacokinetics and Haemostatic Status During Consecutive Infusions of Recom binant Tissue-Type Plasminogen Activator in Patients with Acute Myocardial Infarction

1989 ◽  
Vol 61 (03) ◽  
pp. 497-501 ◽  
Author(s):  
E Seifried ◽  
P Tanswell ◽  
D Ellbrück ◽  
W Haerer ◽  
A Schmidt
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Plasminogen Activator ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Precise Control ◽  
Type Plasminogen Activator

SummaryPharmacokinetics and systemic effects of recombinant tissue type plasminogen activator (rt-PA) were determined during coronary thrombolysis in 12 acute myocardial infarction patients using a consecutive intravenous infusion regimen. Ten mg rt-PA were infused in 2 minutes resulting in a peak plasma concentration (mean ±SD) of 3310±950 ng/ml, followed by 50 mg in 1 h and 30 mg in 1.5 h yielding steady state plasma levels of. 2210±470 nglml and 930±200 ng/ml, respectively. All patients received intravenous heparin. Total clearance of rt-PA was 380±74 ml/min, t,½α was 3.6±0.9 min and t,½β was 16±5.4 min.After 90 min, in plasma samples containing anti-rt-PA-IgG to inhibit in vitro effects, fibrinogen was decreased to 54%, plasminogen to 52%, α2-antiplasmin to 25%, α2-macroglobulin to 90% and antithrombin III to 85% of initial values. Coagulation times were prolonged and fibrin D-dimer concentrations increased from 0.40 to 2.7 μg/ml. It is concluded that pharmacokinetics of rt-PA show low interpatient variability and that its short mean residence time in plasma allows precise control of therapy. Apart from its moderate effect on the haemostatic system, rt-PA appears to lyse a fibrin pool in addition to the coronary thrombus.

Formulation and Evaluation of Mefloquine Hydrochloride Nanoparticles

2014 ◽  
Vol 7 (1) ◽  
pp. 2377-2386
Author(s):  
Dilip Kumar Gupta ◽  
B K Razdan ◽  
Meenakshi Bajpai
Keyword(s):  
Particle Size ◽  
Sustained Release ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Taste Masking ◽  
Diffusion Method ◽  
Drug Entrapment Efficiency ◽  
Resistant Strains ◽  
Vitro Release

The present study deals with the formulation and evaluation of mefloquine hydrochloride nanoparticles. Mefloquine is a blood schizonticidal quinoline compound, which is indicated for the treatment of mild-to-moderate acute malarial infections caused by mefloquine-susceptible multi-resistant strains of P. falciparum and P. vivax. The purpose of the present work is to minimize the dosing frequency, taste masking toxicity and to improve the therapeutic efficacy by formulating mefloquine HCl nanoparticles. Mefloquine nanoparticles were formulated by emulsion diffusion method using polymer poly(ε-caprolactone) with six different formulations. Nanoparticles were characterized by determining its particle size, polydispersity index, drug entrapment efficiency, drug content, particle morphological character and drug release. The particle size ranged between 100 nm to 240 nm. Drug entrapment efficacy was >95%. The in-vitro release of nanoparticles were carried out which exhibited a sustained release of mefloquine HCl from nanoparticles up to 24 hrs. The results showed that nanoparticles can be a promising drug delivery system for sustained release of mefloquine HCl.

Formulation and Evaluation of Itopride Hydrochloride Floating Beads for Gastroretentive Delivery

2013 ◽  
Vol 6 (4) ◽  
pp. 2269-2280
Author(s):  
Nagratna Dhople ◽  
P N Dandag ◽  
A P Gadad ◽  
C K Pandey ◽  
Masthiholimath V S
Keyword(s):  
Sustained Release ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Sustained Release Formulation ◽  
Prokinetic Drug ◽  
Drug Entrapment Efficiency ◽  
Itopride Hydrochloride ◽  
Vitro Release

A gastroretentive sustained release system of itopride hydrochloride was formulated to increase the gastric residence time and modulate its release behavior. Itopride hydrochloride is a prokinetic drug used in the treatment of gastroeosophageal reflux disease, Non-ulcer dyspepsia and as an antiemetic. Hence, itopride hydrochloride beads were prepared by emulsion gelation method by employing low methoxy pectin and sodium alginate as sustained release polymers in three different ratios alone and in combination and sunflower oil was used to enable floating property to the beads. The effect of variation in polymer and their concentration was investigated. The beads were evaluated for production yield, particle size, swelling index, density measurement, buoyancy, drug content, drug entrapment efficiency, in vitro release characteristics and release kinetic study. Based on drug entrapment efficiency, buoyancy, swelling and in vitro release, F9 was selected as the optimized formulation. F9 was further subjected to surface morphology by SEM, in vitro release comparison with marketed formulation, in vivo floating study in rabbits and stability study for 90 days. In vitro release follows zero order and fitted in Korsmeyer peppas model (Non-Fickian release). Therefore, the rate of drug release is due to the combined effect of drug diffusion and polymer swelling. The in vivo X-ray studies revealed that the beads were floating in the rabbit stomach up to 10 hours. Thus, it was concluded that the sustained release formulation containing itopride hydrochloride was found to improve patient compliance, minimize the side effects and decrease the frequency of administration.

scholarly journals Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 904
Author(s):  
Irin Tanaudommongkon ◽  
Asama Tanaudommongkon ◽  
Xiaowei Dong
Keyword(s):  
Sustained Release ◽  
Trough Concentration ◽  
Self Assembly ◽  
Subcutaneous Injection ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Long Acting

Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.

scholarly journals FORMULATION AND EVALUATION OF MUCOADHESIVE MICROSPHERES OF AN ANTI-MIGRAINE DRUG

2018 ◽  
Vol 8 (5) ◽  
pp. 465-474
Author(s):  
S PADMA PRIYA ◽  
AN Rajalakshmi ◽  
P Ilaveni
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Sodium Alginate ◽  
Release Kinetics ◽  
Drug Loading ◽  
Research Work ◽  
Entrapment Efficiency ◽  
Polyvinyl Pyrrolidone ◽  
Anti Migraine Drug

Objective: The objective of this research work is to develop and evaluate mucoadhesive microspheres of an anti-migraine drug for sustained release. Materials and Methods:  Mucoadhesive microspheres were prepared by emulsification method using Sodium alginate (SA), polyvinyl pyrrolidone (PVP) and Chitosan in the various drug-polymer ratios of 1:1, 1:2 and 1:3. Nine  formulations were formulated and  evaluated for  possible drug polymer interactions, percentage yield, micromeritic properties, particle size, drug content, drug entrapment efficiency, drug loading, swelling index, In-vitro wash off test, in vitro  drug release, surface morphology and release kinetics. Results: The results showed that no significant drug polymer interaction in FTIR studies. Among all the formulations SF3 containing sodium alginate showed 77.18% drug release in 6hrs. Conclusion: Amongst the developed mucoadhesive microspheres, SF3 formulation containing sodium alginate exhibited slow and sustained release in a controlled manner and it is a promising formulation for sustained release of Sumatriptan succinate. Keywords: Mucoadhesive microspheres, Sodium alginate, polyvinyl pyrrolidone, Chitosan, sustained release.

scholarly journals Emulsification by TPGS or Quillaja Extract Increased Absorption and Affected Metabolism of Berberine in Humans

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 381-381
Author(s):  
Yavuz Yagiz ◽  
Gary Wang ◽  
Liwei Gu
Keyword(s):  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Total Content ◽  
Compartment Model ◽  
Analysis Of Covariance ◽  
High Tech ◽  
Pharmacokinetic Parameters ◽  
Funding Sources ◽  
Human Volunteers

Abstract Objectives Berberine is a botanical alkaloid used widely for the prevention of several diseases. However, the absorption rate of berberine is less than 1% in human. The objectives of this study were to determine whether emulsification by TPGS or Quillaja extract affect the absorption and metabolism of orally ingested berberine in human volunteers. Methods Twelve healthy subjects (7 male and 5 females, 21–50-year-old) participated this study. Each subject received 800 mg berberine in a powder form or emulsified with TPGS or Quillaja extract using a randomized crossover design with one-week washout period. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after dose. Plasma was hydrolyzed with glucuronidase and sulfatase before total content of berberine and its metabolites were analyzed on LC/MS/MS. Free forms of metabolites were determined in plasma without hydrolysis. Pharmacokinetic parameters were calculated using a non-compartment model before they were compared by analysis of covariance. Results The area under the curve (AUC) and peak plasma concentration (Cmax) of berberine was 6.6 μM.hr and 0.9 μM in participants received berberine powder. They were increased to 18.3 μM.hr and 4.5 μM by TPGS emulsification and 28 μM.hr and 5.1 μM by Quillaja extract emulsification, respectively. Berberrubine and demethylberberine were major metabolites of berberine. The AUC of free Berberrubine and demethylberberine was increased by 1.9 fold and 1.6 fold by TPGS and 5.9 folds and 2.7 folds by Quillaja extract, respectively, compared to berberine powder. Participants received berberine powder had AUC of 254 μM.hr and Cmax of 33 μM for total berberrubine. TPGS emulsification increased these values to 425 μM.hr and 54 μM, while Quillaja extract increased them to 341 μM.hr and 44 μM, respectively. Significant increases of AUC and Cmax were also observed for total demethylberberine by TPGS or Quillaja extract emulsification. Conclusions Emulsification of berberine with TPGS or Quillaja extract significantly increased the absorption of berberine and its metabolites in human compared to berberine supplement without emulsifiers. Funding Sources Florida High Tech Corridor Council and Designs for Health.

Preconditioning with ethanol prevents postischemic leukocyte-endothelial cell adhesive interactions

2002 ◽  
Vol 283 (3) ◽  
pp. H1019-H1030 ◽  
Author(s):  
Taiji Yamaguchi ◽  
Catherine Dayton ◽  
T. Shigematsu ◽  
Patsy Carter ◽  
Toshikazu Yoshikawa ◽  
...  
Keyword(s):  
Temporal Pattern ◽  
Receptor Agonist ◽  
Inflammatory Responses ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Late Phase ◽  
Ethanol Exposure ◽  
Ethanol Ingestion ◽  
Adhesive Interactions ◽  
Ethanol Ethanol

Long-term ethanol consumption at low to moderate levels exerts cardioprotective effects in the setting of ischemia and reperfusion (I/R). The aims of this study were to determine whether 1) a single orally administered dose of ethanol [ethanol preconditioning (EtOH-PC)] would induce a biphasic temporal pattern of protection (early and late phases) against the inflammatory responses to I/R and 2) adenosine and nitric oxide (NO) act as initiators of the late phase of protection. Ethanol was administered as a bolus to C57BL/6 mice at a dose that achieved a peak plasma concentration of ∼45 mg/dl 30 min after gavage and returned to control levels within 60 min of alcohol ingestion. The superior mesenteric artery was occluded for 45 min followed by 60 min of reperfusion beginning 10 min or 1, 2, 3, 4, or 24 h after ethanol ingestion, and the numbers of fluorescently labeled rolling and firmly adherent (stationary) leukocytes in single postcapillary venules of the small intestine were quantified using intravital microscopic approaches. I/R induced marked increases in leukocyte rolling and adhesion, effects that were attenuated by EtOH-PC 2–3 h before I/R (early phase), absent when assessed after 10 min, 1 h, and 4 h of ethanol ingestion, with an even more powerful late phase of protection reemerging when I/R was induced 24 h later. The anti-inflammatory effects of late EtOH-PC were abolished by treatment with adenosine deaminase, an adenosine A2 (but not A1) receptor antagonist, or a NO synthase (NOS) inhibitor during the period of EtOH-PC. Preconditioning with an adenosine A2 (but not an A1) receptor agonist in lieu of ethanol 24 h before I/R mimicked the protective actions of late phase EtOH-PC. Like EtOH-PC, the effect of preconditioning with an adenosine A2 receptor agonist was abrogated by coincident NOS inhibition. These findings suggest that EtOH-PC induces a biphasic temporal pattern of protection against the proinflammatory effects of I/R. In addition, our observations are consistent with the hypothesis that the late phase of EtOH-PC is triggered by NO formed secondary to adenosine A2 receptor-dependent activation of NOS during the period of ethanol exposure.

Floating Microsphere of Curcumin as Targeted Gastro-retentive Drug Delivery System

2021 ◽  
pp. 5202-5206
Author(s):  
Anupam K Sachan ◽  
Saurabh Singh ◽  
Kiran Kumari ◽  
Pratibha Devi
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Sustained Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Entrapment Efficiency ◽  
Synthetic Polymers ◽  
Drug Bioavailability ◽  
Gastric Residence Time

Microspheres carrier system made from natural or synthetic polymers used in sustained release drug delivery system. The present study involves formulation and evaluation of floating microspheres of Curcumin for improving the drug bioavailability by prolongation gastric residence time. Curcumin, natural hypoglycemic agent is a lipophilic drug, absorbed poorly from the stomach, quickly eliminated and having short half-life so suitable to formulate floating drug delivery system for sustained release. Floating microspheres of curcumin were formulated by solvent evaporation technique using ethanol and dichloromethane (1:1) as organic solvent and incorporating various synthetic polymers as coating polymer, sustain release polymers and floating agent. The final formulation were evaluated various parameters such as compatibility studies, micrometric properties, In-vitro drug release and % buoyancy. FTIR studies showed that there were no interaction between drug and excipients. The surface morphology studies by SEM confirmed their spherical and smooth surface. The mean particles size were found to be 416-618µm, practical yield of microspheres was in the range of 60.21±0.052% - 80.87±0.043%, drug entrapment efficiency 47.4±0.065% - 77.9±0.036% and % buoyancy 62,24±0.161% - 88.63±0.413%. Result show that entraptmency increased as polymer (Eudragit RS100) conc. Increased. The drug release after 12 hrs. was 72.13% - 87.13% and it decrease as a polymer (HPMC, EC) concentration was decrease.

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