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INTISARI

Prometazin HCl mengalami efek lintas pertama hepatik sehingga memiliki bioavilabilitas yang relatif rendah yaitu sekitar 25%. Absorbsi oral sering terganggu oleh mual dan muntah, sehingga bioavilabilitas obat semakin rendah dan morning sickness tidak terterapi dengan baik. Penelitian ini bertujuan untuk mengetahui : 1) pengaruh variasi kadar propilen glikol, Tween 80 dan intensitas arus iontoforesis beserta interaksinya terhadap transpor prometazin HCl, 2) menentukan komposisi teoritis formula optimal prometazin HCl dalam sediaan transdermal secara in vitro. Enhancer propilen glikol, Tween 80 dan intensitas arus iontoforesis digunakan sebagai faktor dalam factorial design 23 dengan menggunakan delapan kondisi uji. Efek peningkat penetrasi terhadap transpor prometazin HCl diuji secara in vitro menggunakan sel difusi franz cell like tipe vertikal. Kulit tikus yang digunakan sebagai membran mengalami praperlakuan dengan propilen glikol dan Tween 80 kemudian dilakukan iontoforesis. Prometazin HCl yang tertranspor melalui membran kulit tikus galur wistar diukur dengan metode spektrofotometri pada max 251 nm. Analisis data menggunakan modeling WinSAAM berbasis kompartemen digunakan untuk mengetahui mekanisme transpor dan pengaruh enhancer. Optimasi dilakukan dengan metode factorial design menggunakan software Design Expert 7.1.4. Transpor prometazin HCl dapat dijelaskan dengan model empat kompartemen. Peningkatan konsentrai propilen glikol dan intensitas arus iontoforesis secara signifikan meningkatkan nilai Cp maks, AUC dan AD. Secara teoritis interaksi propilen glikol-iontoforesis secara signifikan meningkatkan nilai Cp maks, AUC dan AD. Peningkatan konsentrasi Tween 80, interaksi Tween 80propilen glikol serta Tween 80-iontoforesis secara signifikan menurunkan nilai Cp maks, AUC dan AD. Berdasarkan harga parameter Cp maks, AUC dan AD komposisi kondisi uji optimal adalah propilen glikol 20%, Tween 1% dan iontoforesis 0,5 mA/cm2. Secara teoritis kondisi tersebut menghasilkan harga Cp maks 775,519 ng/L, AUC 121 ,073 g dan AD 165,686 g.

Kata kunci : prometazin HCl, transdermal, propilen glikol, Tween 80, iontoforesis

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ABSTRACT

Promethazine HCl undergoes extensive hepatic first-pass metabolism following oral administration resulted in a low bioavailability at around 25%. Oral absorption is often interrupted by nausea and vomiting, so the bioavalability is low and morning sickness is not treated verry well. The purposes of this study were to evaluate the : 1) influence of propylene glycol, Tween 80 concentrations as enhancer and iontophoretic current density on the transport of promehtazine HCl, 2) to determine theoretical composition of optimum condition transdermal delivery system of promethazine HCl in transdermal preparation in vitro. Eight condition were prepared according to 23 factorial design employing propylene glycol, Tween 80 and iontophoretic current density. Ehancement effect on transport of prometazin HCl was investigated across hairless rat skin as membrane. The study was carried out by using vertical diffusion cell (franz cell like). Transport of promehtazine HCl across membrane was determined spectrophotometrically at max 251 nm. Data were analysed based on WinSAAM compartement modeling to determine transport kinetics and the effects of enhancers. Optimization was conducted by factorial design using Design Expert 7.1.4 software. Increasing propylene glycol concentration and the current of iontophoretic significantly increased the Cp max, AUC and also the potential of the drug to difuse (AD). Increasing Tween 80 concentration significantly decrease the Cp max, AUC and also AD. Interactions of propylene glycol and iontophoretic current density significantly increase Cp max, AUC and AD. Interaction of Tween 80 and propylene glycol and also interaction of Tween 80 and iontophoretic current density significantly decrease Cp max, AUC and AD. Based on values of Cp max, AUC and AD optimum composition of the condition containing propylene glycol, Tween 80 and iontophoretic current density which have the percentage and current density of 20%, 1% and 0,5 mA/cm2, respectively. Theoritically, this composition has Cp max, AUC and AD value of 775,519 ng/L, 121 ,073 g and 165,686 g.

Keyword : promethazine HCl, transdermal, propylene glycol, Tween 80, iontophoretic

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