In Vivo Evaluation of Oral Dosage Form Performance

Zhou, Honghui; Seitz, Kathleen

doi:10.1016/b978-0-444-53242-8.00016-3

Cited by 4 publications

(2 citation statements)

References 40 publications

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“…As for the post lag time mean dissolution time (“MDT – lag time” calculated by subtracting the lag time from the total mean dissolution time (MDT)), it is the longest with the new method and shortest with the USP method for Walgreens Aspirin, and the longest with the blank FaSSIF method and the shortest with the USP method for Aspirin Protect (see Table ). MDT was calculated by the following expression: where M max is the maximum amount released and M t is the amount released at time t .…”

Section: Resultsmentioning

confidence: 99%

Toward Biopredictive Dissolution for Enteric Coated Dosage Forms

2016

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The aim of this work was to develop a phosphate buffer based dissolution method for enteric-coated formulations with improved biopredictivity for fasted conditions. Two commercially available enteric-coated aspirin products were used as model formulations (Aspirin Protect 300 mg, and Walgreens Aspirin 325 mg). The disintegration performance of these products in a physiological 8 mM pH 6.5 bicarbonate buffer (representing the conditions in the proximal small intestine) was used as a standard to optimize the employed phosphate buffer molarity. To account for the fact that a pH and buffer molarity gradient exists along the small intestine, the introduction of such a gradient was proposed for products with prolonged lag times (when it leads to a release lower than 75% in the first hour post acid stage) in the proposed buffer. This would allow the method also to predict the performance of later-disintegrating products. Dissolution performance using the accordingly developed method was compared to that observed when using two well-established dissolution methods: the United States Pharmacopeia (USP) method and blank fasted state simulated intestinal fluid (FaSSIF). The resulting dissolution profiles were convoluted using GastroPlus software to obtain predicted pharmacokinetic profiles. A pharmacokinetic study on healthy human volunteers was performed to evaluate the predictions made by the different dissolution setups. The novel method provided the best prediction, by a relatively wide margin, for the difference between the lag times of the two tested formulations, indicating its being able to predict the post gastric emptying onset of drug release with reasonable accuracy. Both the new and the blank FaSSIF methods showed potential for establishing in vitro-in vivo correlation (IVIVC) concerning the prediction of Cmax and AUC0-24 (prediction errors not more than 20%). However, these predictions are strongly affected by the highly variable first pass metabolism necessitating the evaluation of an absorption rate metric that is more independent of the first-pass effect. The Cmax/AUC0-24 ratio was selected for this purpose. Regarding this metric's predictions, the new method provided very good prediction of the two products' performances relative to each other (only 1.05% prediction error in this regard), while its predictions for the individual products' values in absolute terms were borderline, narrowly missing the regulatory 20% prediction error limits (21.51% for Aspirin Protect and 22.58% for Walgreens Aspirin). The blank FaSSIF-based method provided good Cmax/AUC0-24 ratio prediction, in absolute terms, for Aspirin Protect (9.05% prediction error), but its prediction for Walgreens Aspirin (33.97% prediction error) was overwhelmingly poor. Thus it gave practically the same average but much higher maximum prediction errors compared to the new method, and it was strongly overdiscriminating as for predicting their performances relative to one another. The USP method, despite not being overdiscriminating, provided poor pr...

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Section: Resultsmentioning

confidence: 99%

Toward Biopredictive Dissolution for Enteric Coated Dosage Forms

2016

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“…Traditionally, model‐independent pharmacokinetic analysis and, in particular, deconvolution methods have been used successfully to characterize the in vivo release kinetics of drugs from this type of formulation, once they have been developed and administered to animals or humans 9–12. However, there is a lack of information concerning the use of simulation methods and model‐independent pharmacokinetic analysis for the optimal design of release rates in SRFs during the initial stages of pharmaceutical development.…”

Section: Introductionmentioning

confidence: 99%

Optimization of Release Kinetics from Sustained-Release Formulations using Model-Independent Pharmacokinetic Simulation

Maderuelo¹,

Zarzuelo

Lanao

2011

Journal of Pharmaceutical Sciences

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Multiple-reaction monitoring (MRM) LC–MS/MS quantitation of venlafaxine and its O-desmethyl metabolite for a preclinical pharmacokinetic study in rabbits

Fazli

Panigrahy

Kumar³

et al. 2022

Sci Rep

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Preclinical pharmacokinetic (PK) studies in animal models during the formulation development phase give preliminary evidence and near clear picture of the PK behavior of drug and/or its dosage forms before clinical studies on humans and help in the tailoring of the dosage form according to the expected and requisite clinical behavior. The present work reports a first of its kind preclinical PK study on extended-release (ER) solid oral dosage forms of venlafaxine (VEN) in New Zealand White rabbits. The VEN is a highly prescribed and one of the safest and most effective therapeutic agents used in the treatment of different types of depression disorders worldwide. The multiple-reaction monitoring (MRM) LC–MS/MS method developed for this purpose demonstrated enough reliability in simultaneously quantitating VEN and its equipotent metabolite O-desmethylvenlafaxine (ODV) in rabbit plasma. The method described uses solid-phase extraction for sample preparation followed by an ultrafast LC–MS/MS analysis. The chromatographic separation was achieved isocratically with a predominantly polar mobile phase by employing RPLC. The triple quadrupole LC/MS/MS system operated in MRM mode used an ESI probe as an ion source in positive polarity. The validation results are within the permissible limits of US FDA recommendations and acceptance criteria for bioanalytical method validation.

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In Vivo Evaluation of Oral Dosage Form Performance

Cited by 4 publications

References 40 publications

Toward Biopredictive Dissolution for Enteric Coated Dosage Forms

Toward Biopredictive Dissolution for Enteric Coated Dosage Forms

Optimization of Release Kinetics from Sustained-Release Formulations using Model-Independent Pharmacokinetic Simulation

Multiple-reaction monitoring (MRM) LC–MS/MS quantitation of venlafaxine and its O-desmethyl metabolite for a preclinical pharmacokinetic study in rabbits

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