Combining biorelevant in vitro and in silico tools to simulate and better understand the in vivo performance of a nano-sized formulation of aprepitant in the fasted and fed states

Litou, Chara; Patel, Nirmal; Turner, David B.; Kostewicz, Edmund; Kuentz, Martin; Box, Karl; Dressman, Jennifer B.

doi:10.1016/j.ejps.2019.105031

Cited by 25 publications

(16 citation statements)

References 39 publications

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“…By contrast, the use of the in vitro solubility of the crystalline API to represent in vivo solubility can result in a large underprediction of absorption [46] , as shown previously, for example, by Litou et al for the bioenabling formulation of aprepitant [4] .…”

Section: Discussionmentioning

confidence: 96%

“…Within the framework of the PEARRL consortium (and as a follow-up to a recently published case example) [4] , the present study aims to combine results obtained with biorelevant in vitro tools with in silico modeling techniques to simulate and better understand the in vivo behavior of the amorphous solid dispersion of etravirine. This formulation of etravirine is commercially available under the brand name Intelence® and its labeling specifies administration in the fed state.…”

Section: Introductionmentioning

confidence: 99%

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Combining biorelevant in vitro and in silico tools to investigate the in vivo performance of the amorphous solid dispersion formulation of etravirine in the fed state

Litou

Turner

Holmstock

et al. 2020

European Journal of Pharmaceutical Sciences

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Combining biorelevant in vitro and in silico tools to investigate the in vivo performance of the amorphous solid dispersion formulation of etravirine in the fed state

Litou

Turner

Holmstock

et al. 2020

European Journal of Pharmaceutical Sciences

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“…Various biorelevant conditions have been shaped to build the IVIVC for orally administered NDDS (Table 4). Biorelevant dissolution coupled with PBPK modeling can support the oral NDDS development and minimize the animal/human testing (Kaur et al, 2018; Litou et al, 2019). However, PBPK modeling of NDDS is very challenging due to complex in vivo transport mechanisms such as MPS uptake, EPR effect, lymphatic transport, and enzyme degradation (Li et al, 2017).…”

Section: Ivivc For Nddsmentioning

confidence: 99%

In vitro dissolution considerations associated with nano drug delivery systems

Gupta

Chen

Xie

2021

WIREs Nanomed Nanobiotechnol

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Nano drug delivery systems (NDDS) offer promising solution for the translation of future nanomedicines. As bioavailability and therapeutic outcomes can be improved by altering the drug release from these NDDS, it becomes essential to thoroughly understand their drug release kinetics. Moreover, U.S. Food and Drug Administration requires critical evaluation of potential safety, efficacy, and public health impacts of nanomaterials. Spiraling up market share of NDDS has also stimulated the pharmaceutical industry to develop their cost‐effective generic versions after the expiry of patent and associated exclusivity. However, unlike the conventional dosage forms, the in vivo disposition of NDDS is highly intricate and different from their in vitro behavior. Significant challenges exist in the establishment of in vitro–in vivo correlation (IVIVC) due to incomplete understanding of nanoparticles' in vivo biofate and its impact on in vitro experimental protocols. A rational design of dissolution may serve as quality and quantity control tool and help develop a meaningful IVIVC for favorable economic implications. Clinically relevant drug product specifications (critical quality attributes) can be identified by establishing a link between in vitro performance and in vivo exposure. In vitro dissolution may also play a pivotal role to understand the dissolution‐mediated clearance and safety of NDDS. Prevalent in vitro dissolution methods for NDDS and their limitations are discussed in this review, among which USP 4 is gaining more interest recently. Researchers are working diligently to develop biorelevant in vitro release assays to ensure optimal therapeutic performance of generic versions of these NDDS. This article focuses on these studies and presents important considerations for the future development of clinically relevant in vitro release methods. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine

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“…Furthermore, the extrapolations made by the physiologically based pharmakokinetic and biodistribution model generates an expected in vivo biodistribution pattern based on early preclinical in vitro and in vivo data. In brief, establishing in vitro–in vivo correlation of nanocrystals can be used to well predict the in vivo behavior of drugs, elucidate the absorption mechanism and reduce the risk of clinical drug use (Bao et al., 2017 ; Litou et al., 2019 ).…”

Section: Solidification Of Nanocrystal Suspensionsmentioning

confidence: 99%

Progress in the development of stabilization strategies for nanocrystal preparations

Wang

Zhang

et al. 2020

Drug Delivery

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In recent years, nanocrystal technology has been extensively investigated. Due to the submicron particle size and unique physicochemical properties of nanocrystals, they overcome the problems of low drug solubility and poor bioavailability. Although the structures of nanocrystals are simple, the further development of these materials is hindered by their stability. Drug nanocrystals with particle sizes of 1∼1000 nm usually require the addition of stabilizers such as polymers or surfactants to enhance their stability. The stability of nanocrystal suspensions and the redispersibility of solid nanocrystal drugs are the key factors for the large-scale production of nanocrystal preparations. In this paper, the factors that affect the stability of drug nanocrystal preparations are discussed, and related methods for solving the stability problem are put forward.

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Combining biorelevant in vitro and in silico tools to simulate and better understand the in vivo performance of a nano-sized formulation of aprepitant in the fasted and fed states

Abstract: Combining biorelevant in vitro and in silico tools to simulate and better understand the in vivo performance of a nano-sized formulation of aprepitant in the fasted and fed states.

Cited by 25 publications

References 39 publications

Combining biorelevant in vitro and in silico tools to investigate the in vivo performance of the amorphous solid dispersion formulation of etravirine in the fed state

Combining biorelevant in vitro and in silico tools to investigate the in vivo performance of the amorphous solid dispersion formulation of etravirine in the fed state

In vitro dissolution considerations associated with nano drug delivery systems

Progress in the development of stabilization strategies for nanocrystal preparations

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