In vitro–in vivo correlations for lipophilic, poorly water-soluble drugs

Dressman, Jennifer B.; Reppas, Christos

doi:10.1016/s0928-0987(00)00181-0

Cited by 498 publications

(302 citation statements)

References 9 publications

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“…Here, we seek to capture the main features of each curve with a minimum number of parameters, allowing rapid characterization. Of course, the use of biological relevant medium and volumes will provide better input (28)(29)(30)(31)(32)(33). To be sure, there is some loss in accuracy when a minimum number of parameters are used to characterize a wide variety of peak shapes.…”

Section: Model Development Parameterization Of In Vitro Drug Concentrmentioning

confidence: 99%

Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs

Kleppe

Forney-Stevens

Haskell

et al. 2015

AAPS J

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Abstract. Poorly soluble drugs are increasingly formulated into supersaturating drug delivery systems which may precipitate during oral delivery. The link between in vitro drug concentration profiles and oral bioavailability is under intense investigation. The objective of the present work was to develop closedform analytical solutions that relate in vitro concentration profiles to the amount of drug absorbed using several alternate assumptions and only six parameters. Three parameters define the key features of the in vitro drug concentration-time profile. An additional three parameters focus on physiological parameters. Absorption models were developed based on alternate assumptions; the drug concentration in the intestinal fluid: (1) peaks at the same time and concentration as in vitro, (2) peaks at the same time as in vitro, or (3) reaches the same peak concentration as in vitro. The three assumptions provide very different calculated values of bioavailability. Using Case 2 assumptions, bioavailability enhancement was found to be less than proportional to in silico examples of dissolution enhancement. Case 3 assumptions lead to bioavailability enhancements that are more than proportional to dissolution enhancements. Using Case 1 predicts drug absorption amounts that fall in between Case 2 and 3. The equations developed based on the alternate assumptions can be used to quickly evaluate the potential improvement in bioavailability due to intentional alteration of the in vitro drug concentration vs. time curve by reformulation. These equations may be useful in making decisions as to whether reformulation is expected to provide sufficient bioavailability enhancement to justify the effort.

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Section: Model Development Parameterization Of In Vitro Drug Concentrmentioning

confidence: 99%

Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs

Kleppe

Forney-Stevens

Haskell

et al. 2015

AAPS J

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“…vi) the surface area of the small intestine is 800 2 cm [8]. vii) the volume of the fluid (bile and other gastrointestinal fluids) inside the GIT is 600 mL under fasted states [9] and viii) the effective transit time of the drug through the intestine is 4hours [10].…”

Section: Dissolution Model For Cylindrical Particlesmentioning

confidence: 99%

Molecular Dynamics Study of Oral Medicine Delivery Rates Attributed by Two Drug Particles’ Shapes

Soong¹,

Lin²

2013

IJBBB

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Abstract-This paper presents an investigation of oral medicine delivery from a non-traditional point of view, namely, delving into the rates of delivery attributed by two different drug particle's shapes in cylindrical and spherical models. The methodology employed is molecular dynamics (MD). The approach leads to the development of an MD computer simulation program for the establishment of generic parametric databases for follow on scientific comparisons on the solubility rates of particle models in various shapes of interests. Einstein's fluctuation-dissipation equation is referred to in the calculation of diffusion coefficients of given particle models within the MD simulation. This also facilitates the study on the impact on solubility and diffusion of oral medicine particles due to the rates of change of radius and of mass with different weights and sizes. In addition, the dependency of solubility on a cylindrical drug particle's aspect ratio as well as the control on the kinetics of drug release based on diffusion speeds are evaluated. The study concludes on a comparison of the solubility of a sphere versus that of a cylinder with the same mass. The results demonstrate that with the same given mass, the solubility of a spherical particle is less than that of the cylindrical shape. It is also revealed that an increase in the diffusion coefficient for a particle with fixed mass will in turn raise its solubility. However, the solubility and the diffusion coefficient of a particle with fixed radius are inversely proportional.

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“…This drug has broad spectrum anti-protozoan activity via inhibition effect in the respiratory chain of parasites including some that cause giardiasis, trichomoniasis, leishmaniasis and toxoplasmosis, water/food-related disease states, as well as malaria (Calvo, Luis Lavandera, Agueeros, & Irache, 2011). Atovaquone is a highly lipophilic substance with a poor solubility including in gastrointestinal fluids (Dressman & Reppas, 2000). When administered via tablet or suspension, atovaquone is irregularly absorbed and it shows a very poor bioavailability (Calvo et al, 2011), however, bioavailability is doubled by the simultaneous intake of food (23% in the fasted state and 47% in the fed state) ("Glaxo Smith Kline," 2010).…”

Section: Cyclodextrinsmentioning

confidence: 99%

Nanotechnology: the word is new but the concept is old. An overview of the science and technology in food and food products at the nanoscale level

Bryksa

Yada

2012

Int. J. Food Stud.

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Food scientists and technologists are actively engaged in examining and developing nanotechnologies for applications such as novel functional ingredients and nutrient delivery systems, safety testing, packaging, and authenticity/authentication at an ever-increasing pace. However, before these new products/technologies are commercialised, rigorous safety testing and risk/benefit analysis are required to ensure that public and environmental concerns are addressed. This review provides an overview of food nanoscience and technology including a brief history, education, definitions pertaining to policy and regulation, and applications. The most recent findings and advances are emphasised, focussing on bioactives' delivery. In addition, proposed directions in the area of nano-based targeting of pathogens for food safety as well as medical foods are discussed. As food nanoscience and technology has been extenisvely reviewed in recent years, specific case examples will be limited to those reported within the past year.

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In vitro–in vivo correlations for lipophilic, poorly water-soluble drugs

Cited by 498 publications

References 9 publications

Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs

Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs

Molecular Dynamics Study of Oral Medicine Delivery Rates Attributed by Two Drug Particles’ Shapes

Nanotechnology: the word is new but the concept is old. An overview of the science and technology in food and food products at the nanoscale level

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