Oral Absorption Enhancement of Cromolyn Sodium Through Noncovalent Complexation

Ding, Xuan; Rath, Parshuram; Angelo, Robert; Stringfellow, Thomas C.; Flanders, Elizabeth; Dinh, Steven M.; Gómez-Orellana, Isabel; Robinson, Joseph R.

doi:10.1007/s11095-004-7671-9

Cited by 37 publications

(26 citation statements)

References 29 publications

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“…SNAC enhanced the oral bioavailability of cromolyn sodium both in animals and human (6,8). This enhancement in oral bioavailability of cromolyn sodium in the presence of SNAC is due to an increase in cromolyn sodium_s permeation through passive transcellular pathway across the intestinal epithelium and also across the Caco-2 monolayer (6,14,18).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have proposed that SNAC may interact non-covalently with drugs to improve their physicochemical properties, mainly lipophilicity for absorption (12)(13)(14). To examine this hypothesis we set two specific aims, the first being to see if a non-covalent interaction exists between SNAC and cromolyn sodium and the second if this interaction leads to increased cromolyn sodium lipophilicity.…”

Section: Discussionmentioning

confidence: 99%

“…In summary the findings of the steady-state fluorescence emission anisotropy study are as follows: Ding et al (14,18) showed that 67 mM SNAC does not significantly increase the permeability of 10 mM Cromolyn across the Caco-2 cell membrane but 83 mM SNAC does. This indicates that SNAC fluidizes the membrane in a concentration dependent manner allowing for cromolyn sodium permeation transcellularly upon fluidization.…”

Section: Membrane Fluidity Measurementsmentioning

confidence: 94%

“…Based on several mechanistic studies at the cellular and subcellular levels it has been concluded that SNAC increases the passive transcellular transport of these molecules across the epithelial membrane without clear damage to the GI tract_s absorption barrier in vivo and in vitro (6,9,11,12). In addition, it has been proposed that SNAC non-covalently interacts with drugs to improve their physicochemical properties, mainly lipophilicity for absorption (12)(13)(14). In this study we examine the hypotheses that SNAC increases the oral bioavailability of a model drug, cromolyn sodium either by increasing the lipophilicity of the drug by non-covalent interaction or by membrane fluidization.…”

Section: Introductionmentioning

confidence: 99%

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Mechanistic Understanding of Oral Drug Absorption Enhancement of Cromolyn Sodium by an Amino Acid Derivative

Alani

Robinson

2007

Pharm Res

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Membrane Fluidity Measurementsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mechanistic Understanding of Oral Drug Absorption Enhancement of Cromolyn Sodium by an Amino Acid Derivative

Alani

Robinson

2007

Pharm Res

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“…Emisphere contends that SNAC enhances absorption by forming a noncovalent complex with the active compound that enables transcellular absorption, without altering tight junctions (20). For proteins, the mechanism may involve a reversible change in protein Table III conformation and protection against degradation prior to absorption.…”

Section: Products In Developmentmentioning

confidence: 99%

Absorption Enhancers: Applications and Advances

Aungst¹

2011

AAPS J

262

119

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Abstract. Absorption enhancers are functional excipients included in formulations to improve the absorption of a pharmacologically active drug. The term absorption enhancer usually refers to an agent whose function is to increase absorption by enhancing membrane permeation, rather than increasing solubility, so such agents are sometimes more specifically termed permeation enhancers. Absorption enhancers have been investigated for at least two decades, particularly in efforts to develop non-injection formulations for peptides, proteins, and other pharmacologically active compounds that have poor membrane permeability. While at least one product utilizing an absorption enhancer for transdermal use has reached the market, quite a few more appear to be at the threshold of becoming products, and these include oral and transmucosal applications. This paper will review some of the most advanced absorption enhancers currently in development and the formulation technologies employed that have led to their success. In addition, a more basic review of the barriers to absorption and the mechanisms by which those barriers can be surmounted is presented. Factors influencing the success of absorption-enhancing formulations are discussed. If ultimately successful, the products now in development should offer noninjection alternatives for several peptide or protein drugs currently only administered by injection. The introduction of new absorption enhancers as accepted pharmaceutical excipients, and the development of formulation technologies that afford the greatest benefit/risk ratio for their use, may create opportunities to apply these enabling technologies more broadly to existing drugs with non-optimal delivery properties.

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Suppression of Problematic Compound Oligomerization by Cosolubilization of Nondetergent Sulfobetaines

et al. 2015

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Numerous small organic compounds exist in equilibrium among monomers, soluble oligomers, and insoluble aggregates in aqueous solution. Compound aggregation is a major reason for false positives in drug screening, and even soluble oligomers can interfere with structural and biochemical analyses. However, an efficient way to manage the equilibrium of aggregation-prone compounds, especially those involved with soluble oligomers, has not been established. In this study, solution NMR spectroscopy was used as a suitable technique to detect compound oligomers in equilibrium, and it was demonstrated that cosolubilization of nondetergent sulfobetaines (NDSBs) can largely suppress compound oligomerization and aggregation by shifting the equilibrium toward the monomers. The rotational correlation time was obtained from the ratio of the selective and nonselective longitudinal NMR relaxation times, which directly and quantitatively reflected the apparent sizes of the compounds in the equilibrium. The rotational correlation time of the aggregation-prone compound SKF86002 (1 mm) was substantially reduced from 0.31 to 0.23 ns by cosolubilization of 100 mm NDSB195. NDSB cosolubilization allowed us to perform successful structural and biochemical experiments with substantially fewer artifacts, which represents a strategy to directly resolve the problematic oligomerization and aggregation of compounds.

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Oral Absorption Enhancement of Cromolyn Sodium Through Noncovalent Complexation

Cited by 37 publications

References 29 publications

Mechanistic Understanding of Oral Drug Absorption Enhancement of Cromolyn Sodium by an Amino Acid Derivative

Mechanistic Understanding of Oral Drug Absorption Enhancement of Cromolyn Sodium by an Amino Acid Derivative

Absorption Enhancers: Applications and Advances

Suppression of Problematic Compound Oligomerization by Cosolubilization of Nondetergent Sulfobetaines

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