Bio-predictive tablet disintegration: Effect of water diffusivity, fluid flow, food composition and test conditions

Radwan, Asma; Wagner, Manfred; Amidon, Gordon L.; Langguth, Peter

doi:10.1016/j.ejps.2013.08.038

Cited by 39 publications

(27 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Solid dosage form disintegration in the human stomach is a complex process depending on both chemical reactions and physical forces. There are various factors affecting disintegration and dissolution of oral solid dosage forms in vivo including fluid composition, fluid viscosity, hydrodynamic flow around the dosage form, and mechanical stress on the dosage form . PhEur suggests a simple device to test in vitro disintegration of oral solid dosage forms consisting of a basket‐rack assembly, which is moved up and down by a motor in an immersion fluid with a constant frequency.…”

Section: Introductionmentioning

confidence: 99%

Computational Fluid Dynamics Simulation of Hydrodynamics and Stresses in the PhEur/USP Disintegration Tester Under Fed and Fasted Fluid Characteristics

Kindgen

Wachtel

Abrahamsson

et al. 2015

Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

Disintegration of oral solid dosage forms is a prerequisite for drug dissolution and absorption and is to a large extent dependent on the pressures and hydrodynamic conditions in the solution that the dosage form is exposed to. In this work, the hydrodynamics in the PhEur/USP disintegration tester were investigated using computational fluid dynamics (CFD). Particle image velocimetry was used to validate the CFD predictions. The CFD simulations were performed with different Newtonian and non-Newtonian fluids, representing fasted and fed states. The results indicate that the current design and operating conditions of the disintegration test device, given by the pharmacopoeias, are not reproducing the in vivo situation. This holds true for the hydrodynamics in the disintegration tester that generates Reynolds numbers dissimilar to the reported in vivo situation. Also, when using homogenized US FDA meal, representing the fed state, too high viscosities and relative pressures are generated. The forces acting on the dosage form are too small for all fluids compared to the in vivo situation. The lack of peristaltic contractions, which generate hydrodynamics and shear stress in vivo, might be the major drawback of the compendial device resulting in the observed differences between predicted and in vivo measured hydrodynamics.

show abstract

Section: Introductionmentioning

confidence: 99%

Computational Fluid Dynamics Simulation of Hydrodynamics and Stresses in the PhEur/USP Disintegration Tester Under Fed and Fasted Fluid Characteristics

Kindgen

Wachtel

Abrahamsson

et al. 2015

Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

show abstract

“…These mechanisms can also be divided into dynamic and static tablet disintegration 30,31. Sucrose solutions in particular have been shown to affect tablet disintegration both by influencing water uptake (static and dynamic disintegration) and hydrodynamics (dynamic disintegration) because of their higher viscosity, and by causing a profound depression of water diffusivity – and therefore lower water uptake – by molecular interactions (eg, hydrogen bonding) between water and sucrose 29,31…”

Section: Resultsmentioning

confidence: 99%

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models

Uebbing¹,

Klumpp²,

Webster³

et al. 2017

DDDT

View full text Add to dashboard Cite

Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer–Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that disintegration can be used as performance test of rapidly disintegrating tablets beyond the FDA criteria. The scientific criteria and justification is that dissolution has to be DPP dependent, originated from active pharmaceutical ingredient characteristics and formulations factors have to be negligible.

show abstract

“…Dissolution and absorption of drug products have been widely reported in pharmaceutical literature (Dahan and others ; Lindenberg and others ; Taupitz and others ; Radwan and others ; Radwan and others ; Courtney and others ). The Biopharmaceutics Classification System (BCS) was suggested by Amidon and others () almost 20 years ago, and has since been adopted by the US Food and Drug Administration (FDA), the European Medicines Agency (EMEA), and the World Health Organization (WHO) to assist in developing bioavailability and bioequivalence standards for immediate‐release oral drug products (Dahan and others ).…”

Section: Introductionmentioning

confidence: 99%

A Proposed Food Breakdown Classification System to Predict Food Behavior during Gastric Digestion

Bornhorst

Ferrua

Singh

2015

Journal of Food Science

View full text Add to dashboard Cite

The pharmaceutical industry has implemented the Biopharmaceutics Classification System (BCS), which is used to classify drug products based on their solubility and intestinal permeability. The BCS can help predict drug behavior in vivo, the rate-limiting mechanism of absorption, and the likelihood of an in vitro-in vivo correlation. Based on this analysis, we have proposed a Food Breakdown Classification System (FBCS) framework that can be used to classify solid foods according to their initial hardness and their rate of softening during physiological gastric conditions. The proposed FBCS will allow for prediction of food behavior during gastric digestion. The applicability of the FBCS framework in differentiating between dissimilar solid foods was demonstrated using four example foods: raw carrot, boiled potato, white rice, and brown rice. The initial hardness and rate of softening parameter (softening half time) were determined for these foods as well as their hypothesized FBCS class. In addition, we have provided future suggestions as to the methodological and analytical challenges that need to be overcome prior to widespread use and adoption of this classification system. The FBCS gives a framework that may be used to classify food products based on their material properties and their behavior during in vitro gastric digestion, and may also be used to predict in vivo food behavior. As consumer demand increases for functional and "pharma" food products, the food industry will need widespread testing of food products for their structural and functional performance during digestion.

show abstract

Bio-predictive tablet disintegration: Effect of water diffusivity, fluid flow, food composition and test conditions

Cited by 39 publications

References 25 publications

Computational Fluid Dynamics Simulation of Hydrodynamics and Stresses in the PhEur/USP Disintegration Tester Under Fed and Fasted Fluid Characteristics

Computational Fluid Dynamics Simulation of Hydrodynamics and Stresses in the PhEur/USP Disintegration Tester Under Fed and Fasted Fluid Characteristics

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models

A Proposed Food Breakdown Classification System to Predict Food Behavior during Gastric Digestion

Contact Info

Product

Resources

About