scholarly journals Development of bio-relevant dissolution method for prognosis of In-vivo performance of Dipyridamole from modified release capsules

2020 ◽  
Vol 11 (2) ◽  
pp. 2340-2349
Author(s):  
Devi Thamizhanban ◽  
Gampa Tulja Rani ◽  
Kathiresan krishnasamy
Keyword(s):  
Oral Administration ◽  
Design Of Experiment ◽  
Generic Drugs ◽  
Test Method ◽  
Dissolution Profile ◽  
Modified Release ◽  
Dissolution Method ◽  
Media Volume

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.

scholarly journals Development of a Dissolution Method for Gliclazide Modified-Release Tablets Using USP Apparatus 3 with in Vitro–in Vivo Correlation

2018 ◽  
Vol 66 (7) ◽  
pp. 701-707 ◽  
Author(s):  
Kerolayne de Castro Bezerra ◽  
Eduardo Costa Pinto ◽  
Lucio Mendes Cabral ◽  
Valéria Pereira de Sousa
Keyword(s):  
Modified Release ◽  
Dissolution Method ◽  
Apparatus 3 ◽  
Usp Apparatus

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

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.

In vitro and in vivo testing and correlation for oral controlled/ modified release dosage forms. report of the 2nd workshop held December 1988, Washington, DC. U.S.A.

1990 ◽  
Vol 14 (1) ◽  
pp. 95-106 ◽  
Author(s):  
Jerome P. Skelly ◽  
Gordon L. Amidon ◽  
William H. Barr ◽  
Leslie Z. Benet ◽  
James E. Carter ◽  
...  
Keyword(s):  
Dosage Forms ◽  
Washington Dc ◽  
Modified Release ◽  
In Vivo Testing

In vitro dissolution method fitted to in vivo absorption profile of rivaroxaban immediate-release tablets applying in silico data

2017 ◽  
Vol 44 (5) ◽  
pp. 723-728 ◽  
Author(s):  
Nathalie R. Wingert ◽  
Natália O. dos Santos ◽  
Sarah C. Campanharo ◽  
Elisa S. Simon ◽  
Nadia M. Volpato ◽  
...  
Keyword(s):  
In Silico ◽  
Immediate Release ◽  
In Vitro Dissolution ◽  
Absorption Profile ◽  
Dissolution Method ◽  
In Vivo Absorption

scholarly journals Evaluation of mutagenicity, genotoxicity and chronic toxicity of antiviral drug imidazolyl ethanamide pentandioic acid in in vitro and in vivo test systems

2021 ◽  
Vol 98 (5) ◽  
pp. 548-557
Author(s):  
E. A. Jain ◽  
D. Pleimes ◽  
A. A. Globenko
Keyword(s):  
Oral Administration ◽  
Chromosomal Aberrations ◽  
Ames Test ◽  
Chronic Toxicity ◽  
Micronucleus Test ◽  
Human Lymphocytes ◽  
Antiviral Drug ◽  
Systemic Exposure

Introduction. The antiviral properties of imidazolyl ethanamide pentandioic acid (IPA), the active compound of the drug product, has been proven in various experimental models. However, the literature data on the toxicological properties of IPA are limited.Purpose. To evaluate mutagenic and genotoxic properties in in vitro and in vivo models, as well as to study the toxicity of IPA following chronic oral administration to rats and dogs.Materials and methods. Mutagenic and genotoxic properties of IPA were assessed using the Ames test, the test of chromosomal aberrations in human lymphocytes, and the micronucleus test in rats. The chronic toxicity of IPA was studied in Sprague Dawley rats and beagle dogs of both sexes, to which IPA was administered orally at doses of 30-300 mg/kg/day for 26 and 39 weeks, respectively.Results and discussion. In the Ames test, the addition of IPA up to the maximum dose (5000 mcg/plate) did not result in the increase in the number of revertant colonies. At a concentration of up to 5000 mcg/ml, IPA did not cause chromosomal aberrations in human leukocytes. At doses doses ≤ 2000 mg/kg, IPA did not increase the amount of micronuclei in the bone marrow of rats. In chronic experiments, animals tolerated the administration of IPA well: the dose without an observed effect (NOEL) for rats and dogs was 300 mg/kg/day.Conclusion. IPA did not show mutagenic and genotoxic properties in standard in vitro and in vivo tests. With chronic oral administration to rats and dogs, NOEL IPA equal to 300 mg/kg/day provided a systemic exposure that was 8-10 and 41-65 times higher than that in humans, respectively. The results obtained allow us to consider the safety profile of the prolonged use in humans as favorable.

scholarly journals Skrining Mekanisme Kerja Daun Malaka (Phyllanthus emblica L.) Sebagai Antidiabetes

2018 ◽  
Vol 1 (3) ◽  
pp. 106-110
Author(s):  
Novi Irwan Fauzi ◽  
Seno Aulia Ardiansyah ◽  
Saeful Hidayat
Keyword(s):  
Mechanism Of Action ◽  
Inhibitory Activity ◽  
Leaf Extract ◽  
Test Method ◽  
Diabetic Rat ◽  
Phyllanthus Emblica ◽  
Insulin Sensitizer ◽  
Water Fraction

Daun malaka (Phyllanthus emblica L.) mempunyai potensi digunakan sebagai alternatif obat antidiabetes. Daun malaka menunjukkan efek hipoglikemia pada tikus yang diinduksi aloksan. Namun, mekanisme kerjanya belum diketahui pasti. Penelitian ini dilakukan dalam rangka skrining mekanisme kerja daun malaka sebagai antidiabetes. Skrining mekanisme kerja dilakukan terhadap fraksi air daun malaka melalui uji aktivitas inhibisi enzim α-glukosidase serta α-amilase secara in vitro dan pengujian aktivitas insulin-sensitizer terhadap ekstrak daun malaka dengan metode tes toleransi insulin secara in vivo. Fraksi air daun malaka menunjukkan aktivitas inhibisi terhadap enzim α-glukosidase serta α-amilase dengan nilai IC50 (Inhibitor Concentration 50) pada kedua enzim tersebut berturut-turut adalah 0,87% dan 8,64% b/v. Pada uji aktivitas insulin sensitizer, pemberian ekstrak daun malaka dapat meningkatkan sensitivitas insulin pada tikus diabet dengan kondisi resistensi insulin. Nilai KTTI pada kelompok tikus diabet yang diberi ekstrak daun malaka dosis 100 dan 500 mg/kgbb tikus (74,89 dan 75,57) lebih tinggi dibandingkan kelompok tikus diabet (38,41) dan kadar glukosa darah yang lebih rendah selama interval waktu pengukuran. Daun malaka telah diketahui mampu meningkatkan sekresi insulin dan pada penelitian ini menunjukkan aktivitas inhibisi enzim α-glukosidase serta α-amilase secara in vitro dan menunjukkan aktivitas insulinsensitizer pada tikus diabet dengan kondisi resistensi insulin.   Malaka leaf (Phyllanthus emblica L.) has the potential to be used as an alternative antidiabetic drug. Malacca leaves showed hypoglycemia effect in rat induced by alloxan. However, the mechanism of action is not yet known. This study was conducted to evaluate the mechanism of action of Malaka leaves as antidiabetic. Screening of the mechanism of action was carried out on the water fraction of Malaka leaf  byinhibitory activity examination  on α-glucosidase and α-amylase by in vitro studyand Evaluation of insulin-sensitizer activity of Maaka leaf leaf extract was conducted by invivo  insulin tolerance test method. Malaka leaf water fraction showed inhibitory activity against the α-glucosidase and α-amylase with IC50 values ​​(Inhibitory Concentration 50)  of0.87% and 8.64% b / v on both enzyme, respectively. The evaluation of insulin sensitizer revelead that administration ofMalaka  leaf extract can increase insulin sensitivity in diabetic rat with insulin resistance.KTTI values ​​in diabetic rats given malaka extract  at the dose of 100 and 500 mg / kg BW (74.89 and 75.57) were higher than diabetics rat (38.41) and the extract also decrease blood glucose levels during measurement time intervals . Malaka leafhas been known to increase insulin secretion and the study showedthe  inhibitory activity on α-glucosidase and α-amylase by in vitro study and showed insulinsensitizer activity in diabetic rat with insulin resistance.

scholarly journals Requirements for Additional Strength Biowaivers for Modified Release Solid Oral Dosage Forms in International Pharmaceutical Regulators Programme Participating Regulators and Organisations: Differences and Commonalities

2021 ◽  
Vol 24 ◽  
pp. 548-562
Author(s):  
Matthias Shona Roost ◽  
Henrike Potthast ◽  
Chantal Walther ◽  
Alfredo García-Arieta ◽  
Ivana Abalos ◽  
...  
Keyword(s):  
Immediate Release ◽  
Dosage Forms ◽  
Oral Dosage ◽  
In Vitro Dissolution ◽  
Quantitative Composition ◽  
Modified Release ◽  
Solid Oral Dosage Forms ◽  
Oral Dosage Forms

This article describes an overview of waivers of in vivo bioequivalence studies for additional strengths in the context of the registration of modified release generic products and is a follow-up to the recent publication for the immediate release solid oral dosage forms. The current paper is based on a survey among the participating members of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Program (IPRP) regarding this topic. Most jurisdictions consider the extrapolation of bioequivalence results obtained with one (most sensitive) strength of a product series as less straightforward for modified release products than for immediate release products. There is consensus that modified release products should demonstrate bioequivalence not only in the fasted state but also in the fed state, but differences exist regarding the necessity of additional multiple dose studies. Fundamental differences between jurisdictions are revealed regarding requirements on the quantitative composition of different strengths and the differentiation of single and multiple unit dosage forms. Differences in terms of in vitro dissolution requirements are obvious, though these are mostly related to possible additional comparative investigations rather than regarding the need for product-specific methods. As with the requirements for immediate release products, harmonization of the various regulations for modified release products is highly desirable to conduct the appropriate studies from a scientific point of view, thus ensuring therapeutic equivalence.

scholarly journals Design and Characterization of Combinational Domperidone-Famotidine Floating Drug Delivery System - In vitro and In vivo studies

2021 ◽  
Vol 62 (2) ◽  
pp. 144-162
Author(s):  
Mounika Chidurala ◽  
Raveendra Reddy J
Keyword(s):  
Drug Release ◽  
Oral Administration ◽  
Quality By Design ◽  
Release Kinetics ◽  
Cost Effective ◽  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Studies

Introduction: The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and releasethe drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach. Method: Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes)wereidentified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23factor experimental design with midpoints was selected for statistical analysis and optimization. Results: HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit’s stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2 of an optimized product when compared to the marketed product. Conclusions: It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula.

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