Use of Enzymatic Activity for Design of Orally Administered Enteric Dosing Forms

Nishihata, Toshiaki; Yamamoto, Kenji; Ishizaka, Mayumi

doi:10.1111/j.2042-7158.1993.tb05632.x

Cited by 5 publications

(3 citation statements)

References 6 publications

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“…The stability of lipid-based formulations in the small intestinal tract was evaluated by the method of Nishihata 8) with some modifications. Briefly, 0.2 ml of each formulation was added to 4 ml of simulated intestinal fluids composed of 10 mM sodium taurocholate and 375 U/ml pancreatic lipase in phosphate-buffered saline (pH 6.5), and the mixture was incubated at 37°C.…”

Section: Stability Of Formulations In the Simulated Intestinal Fluidsmentioning

confidence: 99%

Disposition of Lipid-Based Formulation in the Intestinal Tract Affects the Absorption of Poorly Water-Soluble Drugs

Iwanaga

Kubota

Miyazaki

et al. 2006

Biological & Pharmaceutical Bulletin

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Recently, drug discovery strategies, based on the technology of combinatorial chemistry and high throughput screening, have often produced compounds with poor water-solubility.1,2) Most of those compounds will drop out as candidates at the pre-formulation or formulation study stage because of their low intestinal absorption despite their high pharmacological activity in vitro. Therefore, the investigation of new dosage formulations for poorly water-soluble compounds will contribute to drug development.Since a new oral dosage formulation for an immunosuppressant drug (cyclosporine A), named "Neoral R ", was developed and used clinically, 3) lipid-based formulations 4,5) to improve the oral absorption of poorly water-soluble drugs have received considerable attention in the pharmaceutical industry. Neoral R contains various ingredients to form an emulsion in the intestinal tract and works as a Self-microemulsifying drug delivery system (SMEDDS).6) This system is regarded as an advanced system of lipid-based formulations. As SMEDDS generally consists of lipid(s) and surfactant(s), these components may affect the absorption mechanism of poorly water-soluble drugs. However, the disposition of lipidbased formulation components in the intestinal tract has not yet been clarified.In this study, we investigated the role of lipid-based formulation components for the intestinal absorption of poorly water-soluble drug by focusing on the disposition of the formulation after oral administration. , the mixture of saturated polyglycolized glyceride and mono-or di-fatty acid esters of polyethylene glycol (Lauroyl macrogol-32 glycerides), was a kind gift from Gattefosse (Gennevilliers Cedex, France). All other chemicals used were of analytical grade. MATERIALS AND METHODS MaterialsPreparation of Lipid-Based Formulations SG (M.W. 418.5), an anthraquinone derivative, was used as a poorly water-soluble model compound. This compound is a poorly water-soluble dye, and its logP value was 7.40. Soybean oil emulsion was prepared by the conventional method. 7) Briefly, 3 mg of SG was added to 0.5 ml of soybean oil preheated at 60°C in a hot water bath and dissolved completely. 0.25 ml of Tween 80 and 4.25 ml of distilled water were added to the oil and sonicated at 20 W for 5 min using an Ultrasonic Disrupter UD-201, Tomy Co. (Tokyo, Japan). For SMEDDS, 3 mg of SG was dissolved in 5 ml of Gelucire 44/14 R preheated at 60°C in a hot water bath. It was then cooled down immediately before use because Gelucire 44/14 R becomes semi-solid at room temperature.In Vivo Oral Administration to Rats All animal experiments were approved by the Animal Experimentation Committee of Osaka University of Pharmaceutical Sciences. Male Wistar rats weighing 300-350 g were obtained from Japan SLC, Inc. (Shizuoka, Japan). The day before the experiment, the rats were lightly anesthetized with ether, and were implanted surgically with a combination of Phicon (Fuji Systems Ltd., Tokyo, Japan) and PE50 (Clay Adams, Parsippany, NJ, U.S.A.) in a catheter, which was ins...

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Section: Stability Of Formulations In the Simulated Intestinal Fluidsmentioning

confidence: 99%

Disposition of Lipid-Based Formulation in the Intestinal Tract Affects the Absorption of Poorly Water-Soluble Drugs

Iwanaga

Kubota

Miyazaki

et al. 2006

Biological & Pharmaceutical Bulletin

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“…We have reported that oleaginous vehicles, including glyceride ester, release drugs incorporated in the vehicles by enzymatic (lipase) degradation (Nishihata et al 1986;Yoshitomi et al 1987). We have also reported that PS-80 vehicles incorporating Sudan 11 (poorly water-soluble dye) released Sudan I1 easily in rat small intestine, in spite of no release in rat stomach, after oral dosing (Nishihata et al 1993); i.e. it was considered that the role of the PS-80 vehicle in increasing intestinal absorption of poorly watersoluble drugs was to transport the drug in solution to the small intestinal tract without precipitation in the stomach and to release drug by enzymatic (small intestinal esterase) degradation of vehicle for intestinal absorption.…”

mentioning

confidence: 99%

“…To understand the role of PS-SO as the vehicle, it is necessary to clarify the enhancing effect of PS-80 on the intestinal absorption of poorly water-soluble drugs in the absence of enzymatic degradation of PS-80, and then to investigate the role of esterase on the PS-80 vehicle. In the present study, we investigated the effect of PS-80 on the rat rectal absorption of itazigrel, which is known to have poor water solubility (less than 100ngmL-' (Nishihata et al 1993)), and the effect of esterase co-administered with dosing vehicles containing PS-80.…”

mentioning

confidence: 99%

Enhanced rectal absorption of itazigrel formulated with polysorbate 80 micelle vehicle in rat: role of co-administered esterase

Yamamoto¹,

Shah²,

Nishihata³

1994

Journal of Pharmacy and Pharmacology

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We investigated the effect of esterase on rectal absorption in the rat of itazigrel using polysorbate 80 (PS-80) micelle as a vehicle to overcome the poor aqueous solubility of itazigrel. The itazigrel formulation prepared with PS-80 increased the absorption compared with a 0.25% carmellose sodium suspension, probably by supplying the itazigrel solute to keep a high concentration at the epithelial surface. When esterase was co-administered with the formulations containing PS-80, the absorption of itazigrel from rat rectum was accelerated further, by rapid release of itazigrel from the micelle vehicle after enzymatic degradation of the PS-80 micelle.

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Bioavailability of itazigrel in dogs after oral administration of soft elastic capsules

Yamamoto¹,

Yokohama²,

Emori³

et al. 1994

International Journal of Pharmaceutics

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Use of Enzymatic Activity for Design of Orally Administered Enteric Dosing Forms

Cited by 5 publications

References 6 publications

Disposition of Lipid-Based Formulation in the Intestinal Tract Affects the Absorption of Poorly Water-Soluble Drugs

Disposition of Lipid-Based Formulation in the Intestinal Tract Affects the Absorption of Poorly Water-Soluble Drugs

Enhanced rectal absorption of itazigrel formulated with polysorbate 80 micelle vehicle in rat: role of co-administered esterase

Bioavailability of itazigrel in dogs after oral administration of soft elastic capsules

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