Formulation and in vitro evaluation of self-nanoemulsifying liquisolid tablets of furosemide

AbstractSelf-nanoemulsifying drug delivery systems (SNEDDS) were used to enhance the dissolution rate of furosemide as a model for class IV drugs and the system was solidified into liquisolid tablets. SNEDDS of furosemide contained 10% Castor oil, 60% Cremophor EL, and 30% PEG 400. The mean droplets size was 17.9 ± 4.5 nm. The theoretical model was used to calculate the amounts of the carrier (Avicel PH101) and coating materials (Aerosil 200) to prepare liquisolid powder. Carrier/coating materials ratio of 5/1 was used and Ludipress was added to the solid system, thus tablets with hardness of 45 ± 2 N were obtained. Liquisolid tablets showed 2-folds increase in drug release as compared to the generic tablets after 60 min in HCl 0.1 N using USP apparatus-II. Furosemide loaded SNEDDS tablets have great prospects for further in vivo studies, and the theoretical model is useful for calculating the adequate amounts of adsorbents required to solidify these systems.

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Effect of ketoconazole administration on the pharmacokinetics (PK) and pharmacodynamics (PD) of bortezomib in patients with advanced solid tumors

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.13016 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 13016-13016

Author(s):

G. S. Chatta ◽

M. E. Rader ◽

C. P. Belani ◽

S. Ramalingam ◽

E. X. Chen ◽

...

Keyword(s):

Cell Lymphoma ◽

Proteasome Inhibition ◽

In Vivo Studies ◽

Advanced Malignancies ◽

Significant Difference ◽

Mantle Cell ◽

The Mean ◽

To Receive

13016 Background: Bortezomib (btz; VELCADE) is a first-in-class small molecule proteasome inhibitor used to treat patients with multiple myeloma and mantle cell lymphoma. In vitro and in vivo studies indicate that btz is primarily metabolized by CYP3A4 and CYP2C19. We conducted a study to evaluate the effect of inhibition of CYP3A4 with ketoconazole (keto) on the PK of btz in humans. Methods: The study enrolled patients with advanced malignancies for whom standard therapy was not available. Patients received btz 1.0mg/m2 (IV) on days 1, 4, 8, and 11 of a 21-day cycle, and were randomized to receive keto 400mg (PO) on days 6, 7, 8, and 9 of either the first or second cycle of treatment. Blood samples for plasma btz determination were collected over 72 hours following the Day 8 dose in Cycles 1 and 2. PK parameters were computed non-compartmentally. PD parameters were derived from an Emax model of percentage proteasome inhibition in whole blood. Results: Of the 21 patients enrolled, 13 had sufficient PK sampling in Cycles 1 and 2 to assess the effect of keto on the PK of btz. No statistically significant difference in AUC0–72h for btz ± keto was observed (p=0.2248). The mean AUC0–72h ratio was 1.22 (90% CI, 0.92–1.61). The exposure-PD relationships for btz ± keto were similar (Table). Adverse events were similar in the presence and absence of keto. Conclusions: Although the AUC0–72h difference was not statistically significant, the 90% CI for the AUC0–72h ratio extends beyond the FDA- specified range of 0.80–1.25 for DDI studies, precluding a declaration of no effect. The presence of a strong CYP3A4 inhibitor increased mean btz exposure by only 22% and had no apparent effect on the exposure-PD relationship. [Table: see text] No significant financial relationships to disclose.

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DEVELOPMENT AND EVALUATION OF ORAL ELEMENTARY OSMOTIC PUMP TABLETS FOR ROPINIROLE HYDROCHLORIDE

INDIAN DRUGS ◽

10.53879/id.49.06.p0023 ◽

2012 ◽

Vol 49 (06) ◽

pp. 23-30

Author(s):

S. Patha ◽

◽

P. Dara ◽

S. K Yamsani ◽

R Thadkapally ◽

...

Keyword(s):

Drug Release ◽

Sustained Release ◽

Osmotic Pump ◽

In Vivo Studies ◽

Dissolution Medium ◽

Conventional Tablet ◽

Peg 400 ◽

Ropinirole Hydrochloride

The objective of the present study was to develop a sustained release once a day oral elementary osmotic tablet for ropinirole hydrochloride and evaluate its in vivo performance. The core of elementary osmotic tablet of ropinirole hydrochloride was prepared by compression of mixture consisting of drug,different concentrations of osmogens, and other tablet material. Core tablets were then coated with different concentrations of cellulose acetate and PEG-400. FTIR was used to identify if the excipients are compatible with the drug. All the tablets that were prepared were evaluated for drug release and based on the results an optimum and ideal osmotic pump composition with a zero-order drug release extended for 24 h was proposed and this was considered the optimized formulation. Surface morphology of coated formulation was studied by scanning electron microscopy. The drug release was determined in different pH media and different agitation speeds. The pharmacokinetics of the drug after oral administration of optimized osmotic pump was investigated in rabbits and the data were compared with that of a conventional tablet. In vitro in vivo correlation was determined for the optimized formulation. A suitable and simple sustained release elementary osmotic pump for ropinirole hydrochloride was developed. The release rate was independent of the pH of the dissolution medium and the agitation speeds. In vivo studies with optimized osmotic tablet formulation demonstrated that drug concentration in plasma was maintained for prolonged period and minimized fluctuation. A better in vitro in vivo correlation was achieved with the osmotic tablet. A simple once a day elementary osmotic tablet is feasible for ropinirole hydrochloride.

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ENZYME VARIATION, METABOLIC FLUX AND FITNESS: ALCOHOL DEHYDROGENASE IN DROSOPHILA MELANOGASTER

Genetics ◽

10.1093/genetics/105.3.633 ◽

1983 ◽

Vol 105 (3) ◽

pp. 633-650

Author(s):

Richard J Middleton ◽

Henrik Kacser

Keyword(s):

Metabolic Flux ◽

Mean Value ◽

In Vivo Studies ◽

Standard Errors ◽

In Vitro Activity ◽

Enzyme Variation ◽

Flux Level ◽

The Mean

ABSTRACT Although there are many in vitro studies of enzyme activity of genetic variants at the Adh locus in D. melanogaster, little is known about the corresponding metabolic activity in living flies. We report here such measurements of the metabolic flux in the conversion of ethanol to the two products, CO2 and lipids, for six different active genotypes, containing the predominant naturally recurring alleles and covering a threefold range of in vitro activity. In adult flies we have found nonsignificant differences between genotypes in metabolic flux when estimates for individual genotypes had standard errors of approximately 10% of the mean value. In vitro activities are, therefore, poor predictors of the physiological consequences of enzyme variation since such determinations ignore the interactions inherent in multienzyme systems. We have no evidence that heterozygote show overdominance either at the enzyme or the flux level. Since fitness differences between genotypes must be generated by physiological differences, investigations of polymorphisms should be based on in vivo studies.

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Regulation of vascular endothelial growth factor expression in human endometrium by steroids and hypoxia: In vitro and in vivo studies

Journal of the Society for Gynecologic Investigation ◽

10.1016/s1071-5576(97)86195-3 ◽

1998 ◽

Vol 5 (1) ◽

pp. 69A-69A

Author(s):

A SHARKEY ◽

D CHARNOCKJONES ◽

K DAY ◽

H SOWTER ◽

L SVENSSON ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Human Endometrium ◽

In Vivo Studies ◽

Vascular Endothelial ◽

Factor Expression ◽

Growth Factor Expression ◽

Endothelial Growth Factor

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In vitro and in vivo studies of new cationic Zn(II)‐benzonaphthoporphyrazines as photosensitizers for PDT

Journal of Porphyrins and Phthalocyanines ◽

10.1002/jpp.373.abs ◽

2001 ◽

Vol 5 (8) ◽

pp. 645-651

Author(s):

M. Peeva ◽

M. Shopova ◽

U. Michelsen ◽

D. Wöhrle ◽

G. Petrov ◽

...

Keyword(s):

In Vivo Studies

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Effect of caffeine on theophyliine on cerebral blood flow response to brain activation: In vitro and in vivo studies

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0198 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S198-S198

Author(s):

Joseph R Meno ◽

Thien-son K Nguyen ◽

Elise M Jensen ◽

G Alexander West ◽

Leonid Groysman ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Brain Activation ◽

In Vivo Studies ◽

Blood Flow Response ◽

Flow Response

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Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648988 ◽

1994 ◽

Vol 72 (06) ◽

pp. 942-946 ◽

Cited By ~ 20

Author(s):

Raffaele Landolfi ◽

Erica De Candia ◽

Bianca Rocca ◽

Giovanni Ciabattoni ◽

Armando Antinori ◽

...

Keyword(s):

Molecular Weight ◽

Unfractionated Heparin ◽

Low Molecular Weight Heparin ◽

Primary Source ◽

In Vivo Studies ◽

Low Molecular Weight ◽

Heparin Administration ◽

To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

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Influence of Platelet Membrane Sialic Acid and Platelet-Associated IgG on Ageing and Sequestration of Blood Platelets in Baboons

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649648 ◽

1993 ◽

Vol 70 (04) ◽

pp. 676-680 ◽

Cited By ~ 24

Author(s):

H F Kotzé ◽

V van Wyk ◽

P N Badenhorst ◽

A du P Heyns ◽

J P Roodt ◽

...

Keyword(s):

Sialic Acid ◽

Life Span ◽

Blood Platelets ◽

Senescent Cell ◽

Platelet Membrane ◽

Antigen Complex ◽

The Mean ◽

Aggregation Of Platelets

SummaryPlatelets were isolated from blood of baboons and treated with neuraminidase to remove platelet membrane sialic acid, a process which artificially ages the platelets. The platelets were then labelled with 111In and their mean life span, in vivo distribution and sites of Sequestration were measured. The effect of removal of sialic acid on the attachment of immunoglobulin to platelets were investigated and related to the Sequestration of the platelets by the spleen, liver, and bone marrow. Removal of sialic acid by neuraminidase did not affect the aggregation of platelets by agonists in vitro, nor their sites of Sequestration. The removal of 0.51 (median, range 0.01 to 2.10) nmol sialic acid/108 platelets shortened their life span by 75 h (median, range 0 to 132) h (n = 19, p <0.001), and there was an exponential correlation between the shortening of the mean platelet life span and the amount of sialic acid removed. The increase in platelet-associated IgG was 0.112 (median, range 0.007 to 0.309) fg/platelet (n = 25, p <0.001) after 0.79 (median, range 0.00 to 6.70) nmol sialic acid/108 platelets was removed (p <0.001). There was an exponential correlation between the shortening of mean platelet life span after the removal of sialic acid and the increase in platelet-associated IgG. The results suggest that platelet membrane sialic acid influences ageing of circulating platelets, and that the loss of sialic acid may have exposed a senescent cell antigen that binds IgG on the platelet membrane. The antibody-antigen complex may then provide a signal to the macrophages that the platelet is old, and can be phagocytosed and destroyed.

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