Mechanisms of Surfactant Effects on Drug Absorption

Gibaldi, Milo; Feldman, Stuart

doi:10.1002/jps.2600590502

Cited by 190 publications

(64 citation statements)

References 76 publications

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“…However, no Shokri et al (2001). Similar findings have been reported by other workers (Gibaldi and Feldman 1970). Hence, availability of less quantity of CDL in free form due to its entrapment in micelle seems to be responsible for the observed low permeation of CDL in the presence of GHN concentrations greater than its cmc of 0.75% w/v.…”

Section: In Vitro Permeation Studiessupporting

confidence: 79%

Transdermal Delivery of Carvedilol Containing Glycyrrhizin and Chitosan as Permeation Enhancers: Biochemical, Biophysical, Microscopic and Pharmacodynamic Evaluation

2008

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The present study was aimed at unveiling the influence of glycyrrhizin and chitosan on rat epidermis and to correlate these effects with percutaneous permeation characteristics of carvedilol. The permeation of carvedilol across excised rat epidermis was significantly higher ( p < 0.05) when glycyrrhizin, chitosan, or glycyrrhizin-chitosan mixture was used as a donor vehicle as compared to propylene glycol:ethanol (7:3) mixture. Epidermis obtained after 12 hr treatment of viable rat skin with a glycyrrhizin-chitosan mixture showed significantly higher ( p < 0.05) permeability to carvedilol as compared to that after treatment with glycyrrhizin or chitosan alone. Further, the application of patches containing glycyrrhizin-chitosan mixture resulted in sustained release of carvedilol, which was able to control the hypertension in deoxycorticosterone acetate induced hypertensive rats through 28 hr. Estimation of microconstituents in rat epidermis revealed maximum extraction of cholesterol, sphingosine, and triglycerides after treatment with glycyrrhizin-chitosan mixture. This was manifested in altered lipid and protein-specific thermotropic transitions. Further, increase in intercellular space, disordered lipid structure and corneocyte detachment as observed in SEM and TEM suggests great potential of glycyrrhizin for use as a percutaneous permeation enhancer.

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Section: In Vitro Permeation Studiessupporting

confidence: 79%

Transdermal Delivery of Carvedilol Containing Glycyrrhizin and Chitosan as Permeation Enhancers: Biochemical, Biophysical, Microscopic and Pharmacodynamic Evaluation

2008

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“…Gibaldi and Feldman (1970) reviewed a variety of mechanisms whereby surfactants could alter oral drug absorption. Some surfactants were thought to act by altering the permeability of the intestinal mucosa, while others were believed to increase GI capillary permeability.…”

Section: Discussionmentioning

confidence: 99%

Effect of Emulphor, an Emulsifier, on the Pharmacokinetics and Hepatotoxicity of Oral Carbon Tetrachloride in the Rat

SANZGIRI¹,

BRUCKNER²

1997

Toxicol Sci

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Emulphor, a polyethoxylated vegetable oil, is now being used widely to incorporate volatile organic compounds (VOCs) and other lipophilic compounds into aqueous solutions for biochemical, pharmacokinetic, and toxicological studies. Previous work in this laboratory demonstrated that 0.25% Emulphor did not alter the kinetics or hepatotoxicity of low doses of CCL, compared to when the halocarbon was given to rats orally in water. The present study was undertaken as there was concern that higher concentrations of Emulphor (necessary to maintain lipophilic VOCs in stable aqueous emulsions for extended periods) might alter the VOCs' absorption, disposition, and/or toxidty. Dosages of 10 and 180 mg CCU/kg bw were given, as an aqueous emulsion using 1, 2.5, 5, or 10% Emulphor, by gavage to fasted male Sprague-Dawley rats. Serial microsamples of blood were collected from an indwelling cannula in unanesthetized, freely moving rats at intervals of 2-60 min for up to 12 hr. The samples' CCL, content was measured by headspace gas chromatography. Thereby, it was possible to obtain blood CCL, concentration-versus-time profiles. Animals were euthanized 24 hr postdosing and blood was collected for measurement of serum enzymes as indices of hepatotoxicity. No toxicologically significant differences in pharmacokinetic parameters as a function of Emulphor concentration were found. Similarly the hepatotoxic potency of 10 and 180 mg/kg CCL,, as reflected by elevation in serum enzyme activities, did not vary significantly with the concentration of Emulphor utilized. Hence, it can be concluded that Emulphor, in concentrations as high as 10% (equivalent to 260 mg Emulphor/kg bw) in aqueous emulsions, does not significantly affect the absorption, disposition, or acute hepatotoxicity of CCL, in male Sprague-Dawley rats, o iw sod«y of To

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“…Lecithin and cholesterol are normal components of bile, while fatty acids and monoglycerides are the normal breakdown products of fat digestion, have been shown to form mixed micelles with the conjugated bile salt in the small intestine (Gibaldi & Feldman, 1970). When these substances are present in concentrations higher than their critical micelle concentration, micellar solubilization of the drug can occur (Bates et al, 1966).…”

Section: Equilibrium Solubility In Biorelevant Mediamentioning

confidence: 99%

The physicochemical properties of geraniin, a potential antihyperglycemic agent

Elendran

Wang

Prankerd

et al. 2015

Pharmaceutical Biology

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Context: Natural products play a vital role in the discovery of leads for novel pharmacologically active drugs. Geraniin (GE) was identified as the major compound in the rind of Nephelium lappaceum L. (Sapindaceae), while ellagic and gallic acids have been shown to be its main metabolites. GE and its metabolites possess a range of bioactive properties including being an anti-infective, anticarcinogenic, antihyperglycemic, and antihypertensive. Objective: GE and its metabolites were investigated to establish its gastrointestinal absorption and physicochemical properties. Materials and methods: GE was purified from N. lappaceum rind extract using reverse-phase C18 column chromatography. Lipophilicity (log P) was determined using the 1-octanol/water shakeflask method. Equilibrium solubility of GE and its metabolites (20 mg) was determined in water and four biorelevant media: simulated gastric, simulated intestinal, fasted state-simulated intestinal, and fed state-simulated intestinal after 72 h. Results and discussion: The purification yield was 10.8%; where a 97-99% pure GE was obtained. Log P values for GE, ellagic, and gallic acids were established as À0.73 ± 0.17, 0.11 ± 0.06, and 0.71 ± 0.21, respectively, establishing them as polar compounds. All three compounds were found to exhibit poor solubility in gastric (0.61-8.10 mg/mL) but good solubility in intestinal fluids (3.59-14.32 mg/mL). Conclusion:The above results indicate that the compounds have limited gastrointestinal absorption due to its polarities. To consider these compounds as oral drug candidates, formulation strategies are being developed.

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Mechanisms of Surfactant Effects on Drug Absorption

Cited by 190 publications

References 76 publications

Transdermal Delivery of Carvedilol Containing Glycyrrhizin and Chitosan as Permeation Enhancers: Biochemical, Biophysical, Microscopic and Pharmacodynamic Evaluation

Transdermal Delivery of Carvedilol Containing Glycyrrhizin and Chitosan as Permeation Enhancers: Biochemical, Biophysical, Microscopic and Pharmacodynamic Evaluation

Effect of Emulphor, an Emulsifier, on the Pharmacokinetics and Hepatotoxicity of Oral Carbon Tetrachloride in the Rat

The physicochemical properties of geraniin, a potential antihyperglycemic agent

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