In Vitro Sensitivity Analysis of the Gastrointestinal Dissolution Profile of Weakly Basic Drugs in the Stomach-to-Intestine Fluid Changing System: Explanation for Variable Plasma Exposure after Oral Administration

In-vitro biorelevant dissolution test method was developed for Dipyridamole in modified release multi-particulate dosage form, to simulate the product drug release after oral administration to human. The Dipyridamole concentration in blood plasma achieved after oral administration under pre-prandial (fasting) condition were used for deriving the target dissolution profile deconvoluting the plasma concentration using numerical deconvolution technique. The fraction of drug absorbed was considered as the target dissolution profile. The drug product was tested by using the dissolution method recommended by office of generic drugs, and the dissolution results observed are not comparable with the target dissolution profile. Dissolution method was developed using reciprocating cylinder, Bio-Dis (apparatus -3 as per USP), by simulating the pre-prandial conditions. A full factorial design of experiment was carried out to achieve the target dissolution profile. Media volume and dips per minute (DPM) are considered as main factors, in design of experiment. The dissolution results achieved with media volume 250ml and 10DPM were found to be comparable with target dissolution profile and observed with the F2 value (similarity factor) of 92%. The developed dissolution method demonstrates a very good in-vitro/in-vivo correlation under pre-prandial condition, and shall be used as a predictive in-vitro tool for evaluation Dipyridamole extended release capsules.

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Plasminogen Depletion during Streptokinase Treatment or Two-Chain Urokinase Incubation Correlates with Decreased Clot Lysability Ex Vivo and In Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649714 ◽

1993 ◽

Vol 70 (06) ◽

pp. 0998-1004 ◽

Cited By ~ 13

Author(s):

Páll T Önundarson ◽

H Magnús Haraldsson ◽

Lena Bergmann ◽

Charles W Francis ◽

Victor J Marder

Keyword(s):

Myocardial Infarction ◽

Ex Vivo ◽

Time Dependent ◽

State Variables ◽

Thrombolytic Treatment ◽

Direct Proportion ◽

Plasmin Activity ◽

Plasma Exposure ◽

The Relationship

SummaryThe relationship between lytic state variables and ex vivo clot lysability was investigated in blood drawn from patients during streptokinase administration for acute myocardial infarction. A lytic state was already evident after 5 min of treatment and after 20 min the plasminogen concentration had decreased to 24%, antiplasmin to 7% and fibrinogen 0.2 g/1. Lysis of radiolabeled retracted clots in the patient plasmas decreased from 37 ± 8% after 5 min to 21 ± 8% at 10 min and was significantly lower (8 ± 9%, p <0.005) in samples drawn at 20, 40 and 80 min. Clot lysability correlated positively with the plasminogen concentration (r = 0.78, p = 0.003), but not with plasmin activity. Suspension of radiolabeled clots in normal plasma pre-exposed to 250 U/ml two-chain urokinase for varying time to induce an in vitro lytic state was also associated with decreasing clot lysability in direct proportion with the duration of prior plasma exposure to urokinase. The decreased lysability correlated with the time-dependent reduction in plasminogen concentration (r = 0.88, p <0.0005). Thus, clot lysability decreases in conjunction with the development of the lytic state and the associated plasminogen depletion. The lytic state may therefore limit reperfusion during thrombolytic treatment.

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THE IN VITRO SENSITIVITY PATTERNS PF BACTERIA ISOLATED FROM URINARY TRACT INFECTIONS TO 11 COMMONLY PRESCRIBED ANTIMICROBIAL DRUGS.

Basrah Journal of veterinary Research ◽

10.33762/bvetr.2009.124917 ◽

2009 ◽

Vol 8 (2) ◽

pp. 190-199

Author(s):

Lamyaa Kadhum Bakir

Keyword(s):

Urinary Tract ◽

Urinary Tract Infections ◽

Antimicrobial Drugs ◽

In Vitro Sensitivity ◽

Tract Infections

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PERILAKU DISOLUSI KETOPROFEN DAN INDOMETASIN FARNESIL TERSALUT GEL KITOSAN-GOM GUAR

Jurnal Sains dan Teknologi Indonesia ◽

10.29122/jsti.v12i1.849 ◽

2012 ◽

Vol 12 (1) ◽

Author(s):

Purwantiningsih Sugita ◽

Bambang Srijanto ◽

Budi Arifin ◽

Fithri Amelia ◽

Mahdi Mubarok

Keyword(s):

Room Temperature ◽

Guar Gum ◽

Tween 80 ◽

Chitosan Solution ◽

In Vitro Dissolution ◽

Dissolution Profile ◽

Magnetic Stirrer ◽

Dissolution Behaviour ◽

Shrimp Shell Waste

Chitosan, a modification of shrimp-shell waste, has been utilized as microcapsule. However, it’s fragile gel property needs to be strengthened by adding glutaraldehyde (glu) and natural hydrocolloid guar gum (gg). This research’s purposes were to study dissolution behaviour of ketoprofen and infar through optimum chitosan-guar gum microcapsule. Into 228.6 mL of 1.75% (w/v) chitosan solution in 1% (v/v) acetic acid,38.1 mL of gg solution was added with concentration variation of 0.35, 0.55, and 0.75% (w/v) for ketoprofen microcapsules and 0.05, 0.19, and 0.33% (w/v) for infar microcapsules, and stirred with magnetic stirrer until homogenous. Afterwards, 7.62mL of glu was added slowly under stirring, with concentrations varied: 3, 3.5, and 4% (v/v) for ketoprofen microcapsules, and 4, 4.5, and 5% (v/v) for infar microcapsules. All mixtures were shaked for 20 minutes for homogenization. All mixtures wereshaked for 20 minutes for homogenization. Into each microcapsule mixture for ketoprofen, a solution of 2 g of ketoprofen in 250 mL of 96% ethanol was added, whereas solution of 100 mg of in 250 mL of 96% ethanol was added into each microcapsule mixture for infar. Every mixture was then added with 5 mL of 2% Tween-80 and stirred with magnetic stirrer for an hour at room temperature. Everymixture was then added with 5 mL of 2% Tween-80 and stirred with magnetic stirrer for an hour at room temperature. Conversion of suspension into fine powders/granules (microcapsules) was done by using spray dryer. The data of [gg], [glu], and medicine’s content from each microcapsule were treated with Minitab 14 software to obtain optimum [gg] and [glu] for microencapsulation. The dissolution behaviour of optimum ketoprofen and infar microcapsules were investigated. The result of optimization by using Minitab Release 14 software showed that among the microcapsule compositions of [gg] and [glu] were 0.35% (w/v) and 3.75% (v/v), respectively, optimum to coat ketoprofen, whereas [gg] and [glu] of 0.05% (w/v) and4.00% (v/v), respectively, optimum to coat infar, at constant chitosan concentration (1.75% [w/v]). In vitro dissolution profile showed that chitosan-guar gum gel microcapsule was more resistant in intestinal pH condition (rather basic) compared with that in gastric pH (very acidic).

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Formulation and Evaluation of Immediate Release Bilayer Tablets of Telmisartan and Hydrochlorothiazide

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2011.4.3.6 ◽

2011 ◽

Vol 4 (3) ◽

pp. 1477-1483

Author(s):

Natarajan R ◽

N Patel ◽

Rajendran N N ◽

M Rangapriya

Keyword(s):

Antihypertensive Drugs ◽

In Vitro Release ◽

Immediate Release ◽

Wet Granulation ◽

Physical Parameters ◽

Dissolution Profile ◽

Formulation Development ◽

Sodium Starch Glycolate ◽

Bilayer Tablets

The main goal of this study was to develop a stable formulation of antihypertensive drugs telmisartan and hydrochlorothiazide as an immediate-release bilayer tablet and to evaluate the dissolution profile in comparison with a reference product. The formulation development work was initiated with wet granulation. Telmisartan was converted to its sodium salt by dissolving in aqueous solution of sodium hydroxide to improve solubility and drug release. Lactose monohydrate and microcrystalline cellulose were used as diluents. Starch paste is prepared in purified water and was used as the binder. Sodium starch glycolate is added as a disintegrating agent. Magnesium stearate was used as the lubricant. The prepared granules were compressed into a double-layer compression machine. The tablets thus formulated with higher proportion of sodium starch glycolate showed satisfactory physical parameters, and it was found to be stable and in vitro release studies are showed that formulation (F-T5H5) was 101.11% and 99.89% respectively. The formulation T5H5 is further selected and compared with the release profile of the innovator product, and was found to be similar (f2 factor) to that of the marketed product. The results suggest the feasibility of developing bilayer tablets consisting of telmisartan and hydrochlorothiazide for the convenience of patients with hypertension.

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Atorvastatin-Loaded Oleic Acid Nanoglobules for Oral Administration: In Vitro Characterization and Biopharmaceutical Evaluation

Current Nanoscience ◽

10.2174/1573413711309020007 ◽

2013 ◽

Vol 9 (2) ◽

pp. 202-210

Author(s):

Pradum Pundlikrao Ige ◽

Nilesh Ashok Bachhav ◽

Hitendra Shaligram Mahajan ◽

Pankaj Padmakar Nerkar ◽

Surendra Ganeshlal Gattani

Keyword(s):

Oleic Acid ◽

Oral Administration ◽

In Vitro Characterization

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Red Grape Polyphenol Oral Administration improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200313152648 ◽

2020 ◽

Vol 20 ◽

Author(s):

Thea Magrone ◽

Emilio Jirillo ◽

Manrico Magrone ◽

Matteo Antonio Russo ◽

Paolo Romita ◽

...

Keyword(s):

Contact Dermatitis ◽

Oral Administration ◽

Allergic Contact Dermatitis ◽

Laboratory Data ◽

Anti Oxidant ◽

Anti Inflammatory ◽

Red Grape ◽

Allergic Contact ◽

Drop Outs

Background: Our previous findings demonstrated that in vitro supplementation of polyphenols, extracted from seeds of red grape (Nero di Troia cultivar), to peripheral lymphomonocytes from patients affected by allergic contact dermatitis (ACD) to nickel (Ni) could reduce release of pro-inflammatory cytokines and nitric oxide (NO), while increasing levels of interleukin (IL)-10, an anti-inflammatory cytokine. Objective: To assess whether an intervention with oral administration of polyphenols leads to a reduction of peripheral biomarkers in ACD patients. Method: At T0, 25 patients affected by ACD to Ni were orally administered with 300 mg polyphenols prodie extracted from seeds of red grape (Nero di Troia cultivar) (NATUR-OX®) for 3 months (T1). Other 25 patients affected by ACD to Ni received placebo only for the same period of time. Serum biomarkers were analyzed at T0 and T1. In both groups seven drop outs were recorded. Result: At T1 in comparison to T0, in treated patients, values of IFN-γ, IL-4, IL-17, PTX3 and NO decreased, while IL-10 levels increased when compared with T0 values. Conversely, in placebo-treated patients no modifications of biomarkers were evaluated at T1. Conclusion: Present laboratory data rely on the anti-oxidant, anti-inflammatory and anti-allergic properties of polyphenols.

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In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method

Scientific Reports ◽

10.1038/s41598-021-89671-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Michele Dei Cas ◽

Jessica Rizzo ◽

Mariangela Scavone ◽

Eti Femia ◽

Gian Marco Podda ◽

...

Keyword(s):

Oral Administration ◽

Whole Blood ◽

Serum Levels ◽

Reversed Phase ◽

Weekly Treatment ◽

Low Dose Aspirin ◽

Liquid Chromatography Tandem Mass ◽

Enteric Coated

AbstractLow-dose aspirin (ASA) is used to prevent cardiovascular events. The most commonly used formulation is enteric-coated ASA (EC-ASA) that may be absorbed more slowly and less efficiently in some patients. To uncover these “non-responders” patients, the availability of proper analytical methods is pivotal in order to study the pharmacodynamics, the pharmacokinetics and the metabolic fate of ASA. We validated a high-throughput, isocratic reversed-phase, negative MRM, LC–MS/MS method useful for measuring circulating ASA and salicylic acid (SA) in blood and plasma. ASA-d4 and SA-d4 were used as internal standards. The method was applied to evaluate: (a) the "in vitro" ASA degradation by esterases in whole blood and plasma, as a function of time and concentration; (b) the "in vivo" kinetics of ASA and SA after 7 days of oral administration of EC-ASA or plain-ASA (100 mg) in healthy volunteers (three men and three women, 37–63 years). Parameters of esterases activity were Vmax 6.5 ± 1.9 and Km 147.5 ± 64.4 in plasma, and Vmax 108.1 ± 20.8 and Km 803.2 ± 170.7 in whole blood. After oral administration of the two formulations, tmax varied between 3 and 6 h for EC-ASA and between 0.5 and 1.0 h for plain-ASA. Higher between-subjects variability was seen after EC-ASA, and one subject had a delayed absorption over eight hours. Plasma AUC was 725.5 (89.8–1222) for EC-ASA, and 823.1(624–1196) ng h/mL (median, 25–75% CI) for plain ASA. After the weekly treatment, serum levels of TxB2 were very low (< 10 ng/mL at 24 h from the drug intake) in all the studied subjects, regardless of the formulation or the tmax. This method proved to be suitable for studies on aspirin responsiveness.

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