Biowaiver Approach for Biopharmaceutics Classification System Class 3 Compound Metformin Hydrochloride Using In Silico Modeling

Crison, John R.; Timmins, Peter; Keung, Anther; Upreti, Vijay V.; Boulton, David W.; Scheer, Barry J.

doi:10.1002/jps.23063

Cited by 42 publications

(32 citation statements)

References 25 publications

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“…Metformin pharmacokinetics has been extensively reported by numerous groups (9,(15)(16)(17). It was shown that the 15 13 12 13 13 14 13 30 19 19 19 19 20 19 60 28 28 28 29 29 29 180 51 53 52 54 54 54 360 72 75 75 77 78 77 600 86 92 91 92 92 94 720 91 96 95 97 96 98 N=12, standard deviation was around 1% for all the data.…”

Section: Resultsmentioning

confidence: 86%

“…In order to mitigate the risk of a BE failure, a PK absorption model was used to predict exposure in humans for 1000 mg Met XR. Using the physicochemical and pharmacokinetic properties of metformin, a pharmacokinetic absorption model was developed using GastroPlus™ V.7.0 software (9). Detailed parameters of the model are listed in Table IV.…”

Section: Resultsmentioning

confidence: 99%

“…Using the physicochemical and pharmacokinetic properties of metformin hydrochloride, a pharmacokinetic absorption model was previously developed using GastroPlus™ V.7.0 software (9). The model was used to simulate the mean plasma concentrations for a wide range of drug release profiles and gastric emptying time for a 1000-mg dose of metformin.…”

Section: Methodsmentioning

confidence: 99%

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Mathematical Model-Based Accelerated Development of Extended-release Metformin Hydrochloride Tablet Formulation

Chen

Desai²,

Good³

et al. 2015

AAPS PharmSciTech

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Abstract. A computational fluid dynamic (CFD) model was developed to predict metformin release from a hydroxypropylmethylcellulose (HPMC) matrix-based extended-release formulation that took into consideration the physical and chemical properties of the drug substance, composition, as well as size and shape of the tablet. New high dose strength (1000 mg) tablet geometry was selected based on the surface area/volume (SA/V) approach advocated by Lapidus/Lordi/Reynold to obtain the desired equivalent metformin release kinetics. Maintaining a similar SA/V ratio across all extended-release metformin hydrochloride (Met XR) tablet strengths that had different geometries provided similar simulations of dissolution behavior. Experimental dissolution profiles of three lots of high-strength tablets agreed with the simulated release kinetics. Additionally, a pharmacokinetic absorption model was developed using GastroPlus™ software and known physicochemical, pharmacokinetic, and in vitro dissolution properties of metformin to predict the clinical exposure of the new high strength (1000 mg) tablet prior to conducting a human clinical bioequivalence study. In vitro metformin release kinetics were utilized in the absorption model to predict exposures in humans for new 1000-mg Met XR tablets, and the absorption model correctly projected equivalent in vivo exposure across all dose strengths. A clinical bioequivalence study was pursued based on the combined modeling results and demonstrated equivalent exposure as predicted by the simulations.

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Mathematical Model-Based Accelerated Development of Extended-release Metformin Hydrochloride Tablet Formulation

Chen

Desai²,

Good³

et al. 2015

AAPS PharmSciTech

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“…Argentina adopted these guidelines and published their own guidance documents (10,11). Furthermore, scientists had already recommended the biowaiver extension, and some even considered that BCS Class 3 drugs are more suitable for biowaiver than Class 1 APIs (3,(12)(13)(14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

Pharmaceutical Equivalence and Similarity Studies of Metoclopramide Tablets

Varillas¹,

Brevedan²,

Vidal³

2018

Dissolution Technol.

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Dissolution studies have evolved from a simple quality control test to a surrogate of in vivo interchangeability. Pharmaceutical equivalents are drug formulations with the same molar amount of the same active pharmaceutical ingredient (API), in the same dosage form, meet comparable quality standards, and are intended to be administered by the same route. Pharmaceutical equivalents imply therapeutical equivalence when, after administration, their effects are essentially the same; these effects can be demonstrated by bioequivalence studies or, in some cases, by in vitro studies based on the Biopharmaceutics Classification System. In this scheme, biowaivers are recommended for immediate-release solid oral dosage forms containing Class 3 drugs (like Metoclopramide) using dissolution testing as a surrogate for in vivo bioequivalence studies, with special consideration regarding excipient composition. The present work aimed to compare in vitro dissolution characteristics and other critical quality attributes of Metoclopramide tablets purchased in Argentina to establish their pharmaceutical equivalence and similarity. All evaluated products fulfill the pharmaceutical equivalence criteria. Three of the tested products and the reference formulation complied with the criteria for 'very rapidly dissolving,' so they could be described as essentially similar. Nevertheless, it is important to have access to additional information about the excipient composition of these formulations to assure a safe interchangeability process for this Class 3 drug.

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“…The examples illustrate the pharmaceutics-based risk associated with the API and offer insights into the anticipated outcome from clinical studies. Other major applications in late-phase pharmaceutical product development include the assessment of modified release formulations (17) and making arguments for potential biowaivers of Biopharmaceutics Classification System (BCS) I or III compounds (18)(19)(20)(21) There are several additional areas that computational dissolution/absorption modeling can influence dosage form design and bioperformance. In this article, we discuss five case studies spanning the spectrum of formulation development activities from first-in-human formulation to life cycle management of mature products.…”

Section: Introductionmentioning

confidence: 99%

The Use of Modeling Tools to Drive Efficient Oral Product Design

Mathias

Crison

2012

AAPS J

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Abstract. Modeling and simulation of drug dissolution and oral absorption has been increasingly used over the last decade to understand drug behavior in vivo based on the physicochemical properties of Active Pharmaceutical Ingredients (API) and dosage forms. As in silico and in vitro tools become more sophisticated and our knowledge of physiological processes has grown, model simulations can provide a valuable confluence, tying-in in vitro data with in vivo data while offering mechanistic insights into clinical performance. To a formulation scientist, this unveils not just the parameters that are predicted to significantly impact dissolution/absorption, but helps probe explanations around drug product performance and address specific in vivo mechanisms. In formulation, development, in silico dissolutionabsorption modeling can be effectively used to guide: API selection (form comparison and particle size properties), influence clinical study design, assess dosage form performance, guide strategy for dosage form design, and breakdown clinically relevant conditions on dosage form performance (pH effect for patients on pH-elevating treatments, and food effect). This minireview describes examples of these applications in guiding product development including those with strategies to mitigate observed clinical exposure liability or mechanistically probe product in vivo performance attributes.

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Biowaiver Approach for Biopharmaceutics Classification System Class 3 Compound Metformin Hydrochloride Using In Silico Modeling

Cited by 42 publications

References 25 publications

Mathematical Model-Based Accelerated Development of Extended-release Metformin Hydrochloride Tablet Formulation

Mathematical Model-Based Accelerated Development of Extended-release Metformin Hydrochloride Tablet Formulation

Pharmaceutical Equivalence and Similarity Studies of Metoclopramide Tablets

The Use of Modeling Tools to Drive Efficient Oral Product Design

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