The use of an in vitro dissolution and absorption system to evaluate oral absorption of two weak bases in pH-independent controlled-release formulations

The purpose of this study was to predict in vivo performance of three oral products of Etoricoxib (Arcoxia® as reference and two generic formulations in development) by conducting in vivo predictive dissolution with GIS (Gastro Intestinal Simulator) and computational analysis. Those predictions were compared with the results from previous bioequivalence (BE) human studies. Product dissolution studies were performed using a computer-controlled multicompartmental dissolution device (GIS) equipped with three dissolution chambers, representing stomach, duodenum, and jejunum, with integrated transit times and secretion rates. The measured dissolved amounts were modelled in each compartment with a set of differential equations representing transit, dissolution, and precipitation processes. The observed drug concentration by in vitro dissolution studies were directly convoluted with permeability and disposition parameters from literature to generate the predicted plasma concentrations. The GIS was able to detect the dissolution differences among reference and generic formulations in the gastric chamber where the drug solubility is high (pH 2) while the USP 2 standard dissolution test at pH 2 did not show any difference. Therefore, the current study confirms the importance of multicompartmental dissolution testing for weak bases as observed for other case examples but also the impact of excipients on duodenal and jejunal in vivo behavior.

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Electrospun Janus Beads-On-A-String Structures for Different Types of Controlled Release Profiles of Double Drugs

Biomolecules ◽

10.3390/biom11050635 ◽

2021 ◽

Vol 11 (5) ◽

pp. 635

Author(s):

Ding Li ◽

Menglong Wang ◽

Wen-Liang Song ◽

Deng-Guang Yu ◽

Sim Wan Annie Bligh

Keyword(s):

Controlled Release ◽

Combined Therapy ◽

Diffusion Mechanism ◽

Amorphous State ◽

Electrospinning Process ◽

Fickian Diffusion ◽

In Vitro Dissolution ◽

Sem Images ◽

Release Profiles

A side-by-side electrospinning process characterized by a home-made eccentric spinneret was established to produce the Janus beads-on-a-string products. In this study, ketoprofen (KET) and methylene blue (MB) were used as model drugs, which loaded in Janus beads-on-a-string products, in which polyvinylpyrrolidone K90 (PVP K90) and ethyl cellulose (EC) were exploited as the polymer matrices. From SEM images, distinct nanofibers and microparticles in the Janus beads-on-a-string structures could be observed clearly. X-ray diffraction demonstrated that all crystalline drugs loaded in Janus beads-on-a-string products were transferred into the amorphous state. ATR-FTIR revealed that the components of prepared Janus nanostructures were compatibility. In vitro dissolution tests showed that Janus beads-on-a-string products could provide typical double drugs controlled-release profiles, which provided a faster immediate release of MB and a slower sustained release of KET than the electrospun Janus nanofibers. Drug releases from the Janus beads-on-a-string products were controlled through a combination of erosion mechanism (linear MB-PVP sides) and a typical Fickian diffusion mechanism (bead KET-EC sides). This work developed a brand-new approach for the preparation of the Janus beads-on-a-string nanostructures using side-by-side electrospinning, and also provided a fresh idea for double drugs controlled release and the potential combined therapy.

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In vitro dissolution absorption system (IDAS2): Use for the prediction of food viscosity effects on drug dissolution and absorption from oral solid dosage forms

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2019.105164 ◽

2020 ◽

Vol 143 ◽

pp. 105164

Author(s):

Svitlana Silchenko ◽

Nourdine Nessah ◽

Jibin Li ◽

Li-Bin Li ◽

Yuehua Huang ◽

...

Keyword(s):

Dosage Forms ◽

Drug Dissolution ◽

In Vitro Dissolution ◽

Absorption System ◽

Solid Dosage Forms ◽

Solid Dosage ◽

Viscosity Effects

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Predicting absorption and pharmacokinetic profile of carbamazepine from controlled-release tablet formulation in humans using rabbit model

Veterinarski glasnik ◽

10.2298/vetgl1102071h ◽

2011 ◽

Vol 65 (1-2) ◽

pp. 71-81

Author(s):

Irena Homsek ◽

Dragica Popadic ◽

Slobodanka Simic ◽

Slavica Ristic ◽

Katarina Vucicevic ◽

...

Keyword(s):

Controlled Release ◽

Rabbit Model ◽

Tablet Formulation ◽

Human Model ◽

In Vitro Dissolution ◽

Pharmacokinetic Parameters ◽

Pharmacokinetic Data ◽

Drug Concentrations

Controlled-release (CR) pharmaceutical formulations offer several advantages over the conventional, immediate release dosage forms of the same drug, including reduced dosing frequency, decreased incidence and/or intensity of adverse effects, greater selectivity of pharmacological activity, reduced drug plasma fluctuation, and better compliance. After a drug product has been registered, and is already on market, minor changes in formulation might be needed. At the same time, the product has to remain effective and safe for patients that could be confirmed via plasma drug concentrations and pharmacokinetic characteristics. It is challenging to predict human absorption and pharmacokinetic characteristics of a drug based on the in vitro dissolution test and the animal pharmacokinetic data. Therefore, the objective of this study was to establish correlation of the pharmacokinetic parameters of carbamazepine (CBZ) CR tablet formulation between the rabbit and the human model, and to establish in vitro in vivo correlation (IVIVC) based on the predicted fractions of absorbed CBZ. Although differences in mean plasma concentration profiles were notified, the data concerning the predicted fraction of drug absorbed were almost superimposable. Accordingly, it can be concluded that rabbits may be representative as an in vivo model for predicting the pharmacokinetics of the CR formulation of CBZ in humans.

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