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In-vitro studies to improve microdia...

Long Island University, The Brooklyn Center.

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In-vitro studies to improve microdialysis recovery of a lipophilic drug: Ketoconazole.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	In-vitro studies to improve microdialysis recovery of a lipophilic drug: Ketoconazole./
作者:	Patel, Chanchal.
面頁冊數:	81 p.
附註:	Adviser: Grazia Stagni.
Contained By:	Masters Abstracts International47-02.
標題:	Chemistry, Pharmaceutical. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=1459602
ISBN:	9780549878087

In-vitro studies to improve microdialysis recovery of a lipophilic drug: Ketoconazole.
Patel, Chanchal.

In-vitro studies to improve microdialysis recovery of a lipophilic drug: Ketoconazole. - 81 p.

Adviser: Grazia Stagni.

Thesis (M.S.)--Long Island University, The Brooklyn Center, 2009.

In conclusion, it appears that under physiological conditions the pH 4 lactated ringer's perfusate gives the highest recovery, followed by the Lipo-emulsion, then pH 7.4 buffer solution with 5% BSA, and finally the pH 4 buffer solution with 5% BSA.

ISBN: 9780549878087Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

In-vitro studies to improve microdialysis recovery of a lipophilic drug: Ketoconazole.
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245 1 0 $a In-vitro studies to improve microdialysis recovery of a lipophilic drug: Ketoconazole.
300 $a 81 p.
500 $a Adviser: Grazia Stagni.
500 $a Source: Masters Abstracts International, Volume: 47-02, page: 1021.
502 $a Thesis (M.S.)--Long Island University, The Brooklyn Center, 2009.
520 $a In conclusion, it appears that under physiological conditions the pH 4 lactated ringer's perfusate gives the highest recovery, followed by the Lipo-emulsion, then pH 7.4 buffer solution with 5% BSA, and finally the pH 4 buffer solution with 5% BSA.
520 $a During the last decade microdialysis (MD) has proven to be a very useful technique for the assessment of cutaneous drug delivery and pharmacokinetics of drugs in the skin. Microdialysis is a sampling technique that allows collection of macromolecule-free samples in vivo, continuously and allows repeated sampling at the same site. The microdialysis technique is based on the passive diffusion of substances along their concentration gradients, from the extracellular fluid into the dialysate (1). Because the perfusate is usually an isotonic aqueous solution, only water soluble drugs are sampled by the MD technique. However, most of the drugs that are active in skin diseases are very lipophilic i.e., hormones, antifungals, or antiacne compounds.
520 $a This project explores the possibility of using a modified perfusate in order to improve the recovery of a typical lipophilic drug: Ketoconazole. Ketoconazole was selected as the drug of choice because it is a very lipophilic drug that is administered orally or topically to treat fungal infections in the skin. There are several different challenges faced during the microdialysis sampling of lipophilic molecules. The first difficulty is its inability to collect measurable concentration of a lipophilic molecule in a hydrophilic perfusate, the second challenge is that most lipophilic drugs are highly protein bound and this results in only a small fraction of the actual concentration being in the unbound state and thus available for sampling by the microdialysis fiber. Some of the approaches reported in literature tested to enhance the relative recovery of lipophilic molecules are the use of perfusing media consisting of lipophilic emulsions (lipomicrodialysis), or a physiological solution of albumin, or a solution of cyclodextrins. The present project, aims at improving the MD recovery of ketoconazole by using the lipoemulsion and albumin approaches. In addition, we tried an isotonic water solution at pH 4 in which ketoconazole is freely soluble.
520 $a The HPLC method selected and validated for the determination of ketoconazole consisted of a reverse phase C18 column, a flow rate of 1ml/min, and detection by fluorescence (lambdaex=260 nm and lambdaem=375 nm). The mobile phase consisted of Acetonitrile: 0.05 M Phosphate buffer (50:50). The retention time was typically 4.89 minutes.
520 $a In vitro microdialysis recovery studies were done first under non-physiological conditions at pH 4 in both bulk and perfusate solutions. Then, the bulk solution was made to simulate the Extra Cellular Fluid (ECF): pH 7.4 phosphate buffer in 5% bovine serum albumin (BSA) and a series of different perfusates were tested for recovery studies: (1) pH 4 lactated ringer's solution; (2) pH 4.0 buffer solution with 5% BSA; (3) pH 7.4 buffer solution with 5% BSA; (4) Lipoemulsion-Intralipid 20%.
520 $a Extraction recovery at pH 4 (non-physiological conditions) was 65% showing that when the drug is well soluble the recovery is high and efficient. When the bulk solution simulated the ECF, the Gain/Loss results for the different perfusates: (1) pH 4 lactated ringer's solution; (2) pH 4 buffer solution with 5% BSA; (3) pH 7.4 buffer solution with 5% BSA; (4) Lipoemulsion: Intralipid 20% used were: (1) 35.5 +/- 3.9/76.4 +/- 2.6; (2) 18.6 +/- 0.8/19.4 +/- 0.5; (3) 23 +/- 0.9/22.1 +/- 0.9; (4) 27.4 +/- 1.5/29.3 +/- 1, respectively.
520 $a Results were also corrected for the protein-free ketoconazole, since only the unbound ketoconazole is available to cross the membrane. The corrected Gain/Loss results for the perfusates: (1) pH 4 lactated ringer's solution; (2) pH 4 buffer solution with 5% BSA; (3) pH 7.4 buffer solution with 5% BSA; (4) Lipoemulsion: Intralipid 20% were: (1) 84.1 +/- 3.6/76.7 +/- 2.6; (2) 44.6 +/- 1.9/46.8 +/- 1.2; (3) 57.2 +/- 1.3/55.3 +/- 2.2; (4) 68.9 +/- 8.7/29.3 +/- 1 respectively.
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