Effect of Complex Formation on Drug Absorption III: Concentration- and Drug-dependent effect of a Nonionic Surfactant

Levy, Gerhard; Miller, Karen E.; Reuning, Richard H.

doi:10.1002/jps.2600550409

Cited by 66 publications

(4 citation statements)

References 8 publications

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“…Various formulation strategies have been developed to improve the apparent aqueous solubility and dissolution behavior of poorly water-soluble drugs. Drug–cyclodextrin and drug–surfactant associations are the commonly used formulation strategies. − In the drug–cyclodextrin or drug–surfactant complexes, the excipients consisting of a nonpolar cavity interior and a polar exterior surface function as a molecular cage to “load” drugs, and the complexes themselves are soluble in aqueous media . However, a mechanistic association between a hydrophobic drug and a hydrophilic polymer has been rarely investigated or optimized for the increasing aqueous solubility of the drug.…”

Section: Introductionmentioning

confidence: 99%

Investigating the Association Mechanism between Rafoxanide and Povidone

Meng

Jing

Ferreira³

et al. 2018

Langmuir

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The low aqueous solubility of most hydrophobic medications limits their oral absorption. An approach to solve this problem is to make a drug−polymer association. Herein, we investigated the association between rafoxanide (RAF), a surface-active, poorly water-soluble drug, with a commercial hydrophilic polymer povidone. We found that the association is a function of medium composition and could only take place in polar media, such as water. The association is favored by the hydrogen-bond formation between the amide group in RAF and the carbonyl group in povidone. In addition, the association is also favored by the self-association of RAF through π−π interaction between the benzene rings in adjacent RAF molecules. Twodimensional nuclear magnetic resonance has been applied to investigate the interactions and has confirmed our hypotheses. Geometry optimization confirmed that RAF exists primarily in the antiparallel configuration in the RAF aggregates. This study provides critical information for designing suitable drug−vehicle complexes and engineering the interactions between them to maximize the oral absorption. Our results shed light on drug design and delivery, drug molecule structure−functionality relationship, as well as efficacy enhancement toward interaction engineering.

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Section: Introductionmentioning

confidence: 99%

Investigating the Association Mechanism between Rafoxanide and Povidone

Meng

Jing

Ferreira³

et al. 2018

Langmuir

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“…Surfactants have been reported to increase the absorption of sulfisoxazole (18), secobarbital (22), griseofulvin (4), and hexestrol (4), presumably by dis solving the water-insoluble drug in the hydrophobic interior of the surfactant micelle. Dissolution could thus be promoted by either an increased 'wetting' of the drug by the gastric juice or by precipitation of the drug as a fine dispersion on subsequent disruption of the surfactant micelle.…”

Section: Importance O F Solubility In the Bioavailability O F Drugsmentioning

confidence: 99%

Mechanisms of Drug Absorption and of Drug Solution

Jollow¹,

Brodie²

1972

Pharmacology

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“…Unintentional and unanticipated interactions of drugs with other constituents of their dosage form, with ingested food or other normal constituents of the gastrointestinal tract, or with other drugs may lead to the formation of poorly absorbed complexes and consequent drug inactivation. The poor absorption of tetracyclines in the presence of calcium ( KUNIN & FI"D 1961) et al 1966;ANELLO & LEVY 1969), and the complex of prednisone with certain N,N-dialkylpropionamides which is more rapidly absorbed than the free steroid ( HAYTON et al 1970).…”

mentioning

confidence: 99%

Effect of Complex Formation on Drug Absorption

Levy

1971

Acta Pharmacologica et Toxicologica

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T h e intestinal absorption of certain water-soluble acidic dyes (bromthymol blue, methyl orange, and e0sine-B) and some of their lipoid-soluble complexes has been investigated. T h e results of these studies show that the ap arent lipoid-water paniplexes investigated.tion coefficient does not reflect the intestinal absorption c g aracteristics of the com- of the solutions and the buffer systems used were as follows: for bromthymol blue, pH 7.5 phosphate; for methyl orange, pH 5.0 acetate; for eosine-B, pH 7.0 phosphate. The solutions used for the intestinal absorption studies contained 1 m M dye and 10 m M complexing agent, unless solubility problems required the use of lower concentrations of one or both components. The final pH of these solutions was adjusted, if necessary, with hydrochloric acid or sodium hydroxide. EXPERIMENTALIntestinal Absorption Study.-Intestinal absorption of the dyes and dye complexes was studied by the cannulated everted intestine method developed by Crane and Wilson (6). Male Sprague-Dawley rats, weighing about 250 Gm.. were fasted for 24 hr. but had access to drinking water a t all times. The small intestine was removed under ether anesthesia and rinsed with Ringer solution. The intestine was then sleeved onto a glass rod and everted carefully. Two segments of 10 cm. length (when stretched slightly by attaching a 8 Gm. weight and suspending the segment vertically) were obtained, distal ends were tied, and proximal ends were attached to the cannula of the apparatus described by Crane and Wilson (6). An equal number of first (from the proximal end) and second intestinal segments was used in every part of each experiment. Each segment was suspended in 45 ml. of dye or dye-complex solution maintained at 37' and gassed contixiuously with a mixture of %yo oxygen and 5y0 carbon dioxide. The serosal (inner) solution consisted of 2 ml. buffer solution (for dye absorption studies) or buffer solution with complexing agent (for dyecomplex absorption studies). At indicated times, the entire serosal solution was withdrawn by means of a hypodermic syringe with attached polyethylene cannula and the segment was rinsed twice with about 1 ml. of buffer solution. A fresh 2-ml. portion of buffer solution was then placed in the intestine segment. The initially withdrawn serosal solution and the washings were combined, and water was added t o obtain a total volume of 5 ml. This solution was then filtered through membranes (Millipore, type HA) if necessary, and assayed as indicated.Analytical Methods.-Bromthymoi blue was determined spectrophotometrically at 617 mp in aqueous solutions alkalized by addition of 0.1 N sodium hydroxide. Aminopyrine and codeine did not affect the assay. Bromthymol blue in organic solvent (used in determination of partition coefficients) was extracted into 0.1 N sodium hydroxide and determined as described above.Methyl orange in aqueous solution was determined by employing a modification of Dill's method 1003

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Effect of Complex Formation on Drug Absorption III: Concentration- and Drug-dependent effect of a Nonionic Surfactant

Cited by 66 publications

References 8 publications

Investigating the Association Mechanism between Rafoxanide and Povidone

Investigating the Association Mechanism between Rafoxanide and Povidone

Mechanisms of Drug Absorption and of Drug Solution

Effect of Complex Formation on Drug Absorption

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