Physicochemical and Physiological Mechanisms for the Effects of Food on Drug Absorption: The Role of Lipids and pH

Charman, William N.; Porter, Christopher John; Mithani, Sabena Dawoodali; Dressman, Jennifer B.

doi:10.1021/js960085v

Cited by 546 publications

(374 citation statements)

References 228 publications

Supporting

Mentioning

343

Contrasting

Unclassified

Order By: Relevance

“…The physical and physiochemical factors tested with values obtained were pH (2.3 -6.8), ionic strength (0.08 -0.2 M), surface tension (41 -72 mN/m), osmolarity (190 -600 mOsM) and viscosity (1 -280 mPas). It was observed that these values were within the limits or ranges of previous work done [23,95]. The different variations produced by the factorial design used in this study affected the erosion rates of the dosage forms of the two drugs.…”

Section: Effect Of Food On Drug Relelasesupporting

confidence: 76%

“…Two major properties of the GI fluids are ionic strength and pH [91,95,166]. These two proper-ties vary greatly along the GI tract under fasted and fed conditions [91,95,166].…”

Section: Numerous Other In-vitromentioning

confidence: 99%

“…Two major properties of the GI fluids are ionic strength and pH [91,95,166]. These two proper-ties vary greatly along the GI tract under fasted and fed conditions [91,95,166]. These factors may affect the rate at which a drug is released from its hydrophilic gel matrix [6][7][8][9][10]165,167,168].…”

Section: Numerous Other In-vitromentioning

confidence: 99%

See 2 more Smart Citations

Drug release from matrix tablets: physiological parameters and the effect of food

Nokhodchi

Asare-Addo

2014

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

Introduction: As dissolution plays an important and vital role in the drug-delivery process of oral solid dosage forms, it is, therefore, essential to critically evaluate the parameters that can affect this process. Areas covered:The consumption of food as well as the physiological environment and properties of the gastrointestinal tract, such as its volume and composition of fluid, the fluid hydrodynamics, properties of the intestinal membrane, drug dose and solubility, pK a , diffusion coefficient, permeability and particle size, all affect drug dissolution and absorption rate. There are several dissolution approaches that have been developed to address the conditions as experienced in the in vivo environment, as the traditional dissolution being a quality control method is not biorelevant and as such do not always produce meaningful data. This review also describes the development of a systematic way that differentiates between robust and non-robust formulations by varying the effects of agitation and ionic strength through the use of the automated United States Pharmacopeia type III Bio-Dis apparatus. Expert opinion:With the improved understanding of the physiological parameters that can affect the oral bioperformance of dosage forms, strides have, therefore, been made in making dissolution testing methods more bio-logically based with the view of obtaining more in vitro--in vivo correlations.Keywords: agitation rate, biodissolution, drug release, effect of food, hydrophilic matrices, ionic strength Highlights -Understanding all the physiological parameters can serve as a basis for designing dissolution testing methods and systems that can more fully represent the gastrointestinal (GI) tract in humans and allow more in vitro-in vivo (IVIVC) correlations to be obtained thereby improving the oral bioperformance of dosage forms.-Simulation of GI conditions is essential to adequately predict the in vivo behaviour of drug formulations.-The choice of appropriate media for in vitro tests is crucial to their ability to correctly forecast the food effect in pharmacokinetic studies.-Several methods of dissolution testing have been conducted and are still ongoing that seek to further understand and develop media and dissolution methods to better represent the in vivo conditions and to aid in the better prediction of in vivo drug release.-Systematic change of agitation method and ionic strength evaluation may be used as additional tools in allowing for the identification of potential fed and fasted effects on drug release from hydrophilic matrices in the drive for developing dissolution methodologies that are more relevant in helping to achieve more IVIVC.

show abstract

Section: Effect Of Food On Drug Relelasesupporting

confidence: 76%

“…Two major properties of the GI fluids are ionic strength and pH [91,95,166]. These two proper-ties vary greatly along the GI tract under fasted and fed conditions [91,95,166].…”

Section: Numerous Other In-vitromentioning

confidence: 99%

See 1 more Smart Citation

Drug release from matrix tablets: physiological parameters and the effect of food

Nokhodchi

Asare-Addo

2014

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

show abstract

“…The enzyme is not active at lower pH, but the activity increases nonmonotonically with pH (15); in the duodenum (low pH), it is inactive, whereas in the lower small intestinal track (high pH), it becomes active (15,16). The inactivity of the enzyme at lower pH is known to be related to the protonation of the residues of the catalytic triad (15).…”

mentioning

confidence: 99%

Ultrafast surface hydration dynamics and expression of protein functionality: α-Chymotrypsin

Pal

Peón

Zewail

2002

Proc. Natl. Acad. Sci. U.S.A.

117

138

View full text Add to dashboard Cite

We report studies of hydration dynamics at the surface of the enzyme protein bovine pancreatic ␣-chymotrypsin. The probe is the well known 1-anilinonaphthalene-8-sulfonate, which binds selectively in the native state of the protein, not the molten globule, as shown by x-ray crystallography. With femtosecond time resolution, we examined the hydration dynamics at two pHs, when the protein is physiologically in the inactive state (pH 3.6) or the active state (pH 6.7); the global structure and the binding site remain the same. The hydration correlation function, C(t), whose decay is governed by the rotational and translational motions of water molecules at the site, shows the behavior observed in this laboratory for other proteins, Subtilisin Carlsberg and Monellin, using the intrinsic amino acid tryptophan as a probe for surface hydration. However, the time scales and amplitudes vary drastically at the two pHs. For the inactive protein state, C(t) decays with an ultrafast component, close to bulk-type behavior, but 50% of the C(t) decays at a much slower rate, ‫؍‬ 43 ps. In contrast, for the active state, the ultrafast component becomes dominant (90%) and the slow component changes to a faster decay, ‫؍‬ 28 ps. These results indicate that in the active state water molecules in the hydration layer around the site have a high degree of mobility, whereas in the inactive state the water is more rigidly structured. For the substrate-enzyme complex, the function and dynamics at the probe site are correlated, and the relevance to the enzymatic action is clear.A lmost all biological macromolecules (proteins, enzymes, and DNA) are inactive in the absence of water. The hydration shell formed by water molecules in close vicinity of a protein͞ enzyme is particularly important for the stability of the structure and the function or recognition at a specific site. This role of hydration in enzyme catalysis is well known and has recently been reviewed in a number of publications (see, e.g., refs. 1-3). In one of these studies it was shown that the dehydration of a protein, which makes it more rigid and increases its denaturation temperature, is correlated with the loss of its physiological function (1). An understanding of the dynamics of water molecules at the surface of the protein, with spatial molecular and temporal femtosecond resolution of a single site, is important for elucidating a molecular picture and was the goal of a series of publications from this laboratory (4-6).Using the intrinsic single-tryptophan amino acid as a probe (4, 5), we found that the hydration dynamics at the surface of two different proteins, Subtilisin Carlsberg (SC) (4) and Monellin (5), occur on two well separated time scales: 800 fs and 38 ps for SC and 1.3 ps and 16 ps for Monellin. The slow and fast components are of similar magnitude. From these results, we discussed two types of water hydration trajectories: one fast, bulk type and another much slower, surface-bound type. When these experiments were made on a probe away from the surface by Ϸ1...

show abstract

“…[63][64][65][73][74][75] O teor lipídico presente nos alimentos e a presença de sais biliares também podem melhorar o desempenho de um fármaco lipofílico/hidrofóbico in vivo. [111][112][113][114][115] No entanto, o efeito destes agentes de solubilização na solubilidade do cocristal geralmente não é tão simples. Cocristais farmacêuticos são geralmente compostos por um fármaco hidrofóbico e um coformador relativamente hidrofílico.…”

Section: Agentes Solubilizantesunclassified

Cocristais: uma estratégia promissora na área farmacêutica

et al. 2016

View full text Add to dashboard Cite

COCRYSTALS: A PROMISING STRATEGY IN PHARMACEUTICAL SCIENCES. Pharmaceutical cocrystals have emerged as a useful strategy to improve the aqueous solubility of poorly water soluble drugs by aiming to enhance their oral absorption and bioavailability. Aqueous cocrystal solubility can be orders of magnitude higher than that of the constituent drug and this solubility advantage can be fine-tuned based on environmental conditions such as pH and the presence of drug solubilizing agents. This review presents a brief overview of pharmaceutical cocrystals regarding cocrystal design, obtainment methods, with particular focus on cocrystal solubility, and the solubility modulation by solution phase chemistry.Keywords: cocrystals; drug; solubility; transition point; thermodynamic stability. INTRODUÇÃOO setor de fármaco-medicamentos representa uma área estratégica sob o ponto de vista tecnológico/produtivo nacional. Vários são os desafios da produção de medicamentos competitivos e de qualidade no Brasil, como a oferta de insumos, a pesquisa de novas moléculas ativas e a sua inserção no mercado. Neste sentido, a utilização de inovações incrementais surge como alternativa à problemática do setor, destacando-se a manipulação da forma cristalina dos fármacos, síntese de polimorfos, sais, complexos e, mais recentemente, os cocristais. 1 Cocristais são materiais cristalinos homogêneos, compostos por dois ou mais compostos em proporção estequiométrica definida e que são sólidos em condições ambientes (25 ºC/1 atm). 2,3 Ao longo das últimas décadas, os cocristais têm recebido atenção significativa por parte da indústria farmacêutica, e diversos cocristais farmacêuticos têm sido relatados. Cocristais farmacêuticos, por sua vez, são compostos por um ingrediente farmacêutico ativo (IFA) e uma molécula não tóxica ou outro IFA, chamado de coformador. Ligações de hidrogênio entre as moléculas neutras do fármaco e do coformador orientam a formação do cocristal. 2,4 A síntese de cocristais tem sido uma estratégia cada vez mais utilizada para melhorar a solubilidade, a taxa de dissolução in vitro, e consequentemente, a biodisponibilidade de fármacos pouco solúveis, sem a necessidade de mudar a estrutura molecular e/ou a interação farmacológica. [5][6][7] No entanto, a avaliação da solubilidade e estabilidade dos cocristais em solução ainda não está consolidada. Um levantamento realizado no período de 1999 a 2015 (Figura 1) revelou um crescente número de publicações envolvendo a síntese e a caracterização dos cocristais, mas um reduzido número de publicações envolvendo outros aspectos essenciais no desenvolvimento de formulações contendo cocristais, como estudos de solubilidade, química em solução, estabilidade e a influência de excipientes.Considerando que a baixa solubilidade aquosa é um dos principais problemas associados às entidades químicas farmacêuticas, os

show abstract

Physicochemical and Physiological Mechanisms for the Effects of Food on Drug Absorption: The Role of Lipids and pH

Cited by 546 publications

References 228 publications

Drug release from matrix tablets: physiological parameters and the effect of food

Drug release from matrix tablets: physiological parameters and the effect of food

Ultrafast surface hydration dynamics and expression of protein functionality: α-Chymotrypsin

Cocristais: uma estratégia promissora na área farmacêutica

Contact Info

Product

Resources

About