Studies on the Phase Diagrams of TPGS Based Microemulsion Systems and Their Pharmaceutical Applications
| Autor: | Wen-Ting Ke, 柯文庭 |
|---|---|
| Rok vydání: | 2005 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 93 This dissertation is composed of two parts of studies; the title of part I is “Studies on the Phase Diagrams of D--Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) Based Microemulsion Systems” and that of part II is “Physical Characterization of Self-Microemulsifying Drug Delivery System for Fenofibrate”. Attempts in part I of the dissertation were to develop microemulsion systems using medium chain triglyceride (MCT), Captex 300, deionized water (H2O), and TPGS as surfactant for the oral delivery of protein drugs or poorly water soluble drugs. Pseudo-ternary phase diagrams were constructed to elucidate the phase behavior of systems composed of medium-chain triglyceride and water with TPGS as main surfactant, polysorbates (Tween 20, Tween 40, Tween 60 and Tween 80) as adjuvant surfactants, and polyethylene glycols (PEG 400 and PEG 600) and polyols (ethanediol, 1,2-propanediol, 1,3-propanediol, 1,3-butanediol, 1,4-butanediol and glycerin) as cosurfactants. The weight ratios of TPGS to Tweens, PEGs or polyols (Km) were set at 4/1, 2/1, 1/1, 1/2, and 1/4. The phase diagram for H2O/Captex 300/TPGS system reveals that when TPGS was used as a sole surfactant, it is not capable of producing isotropic solutions of water and Captex 300 over a wide range of the compositions. H2O/Captex 300/TPGS/Tweens systems with various Km, regardless of the adjuvant surfactant used were capable of producing an isotropic phase. The extension of microemulsion phase and the presence and extension of the gel phase were found to be dependent on the surfactant mixture. The phase diagrams of H2O/Captex 300/TPGS systems using polyols as cosurfactants demonstrate that the types of polyols have a slight effect on the region of existence of the microemulsions. Comparison between the isotropic regions for the polyols system reveals that as the relative concentration of polyols increase, the isotropic region decrease in size. This decrease is towards the surfactant mixture (Smix)-water axis indicating that as the relative concentration of polyols increases the maximum amount of oil solubilized decreases. The gel region decreased in size with the increase of polyols weight ratio. All polyols do not solubilized Captex 300 without using TPGS as surfactant. The part II of this dissertation is the application of the studies of part I. Attempts in part II of the dissertation were to develop and characterize the self-microemulsifying drug delivery systems (SMEDDSs) for poorly water soluble drugs. Fenofibrate (an effective agent for the treatment of various types of dyslipidemia) was selected as a model drug that was formulated in a Myritol 318 and nonionic surfactant mixtures of TPGS and polysorbates (Tween 20 or Tween 80), which exhibited self-microemulsifying characteristics under conditions of gentle agitation in an aqueous medium. Using TPGS/Tween 20 as the mixture of surfactant (Smix) at a Km value of 1/4 was found to yield the desired SMEDDSs for fenofibrate. In vitro dissolution studies illustrated that the release of fenofibrate from SMEDDSs was complete within 30 minutes either in 0.025 M SLS solution or water medium. But the release of fenofibrate from Tricor® tablets or micronized fenofibrate dispersion systems (MDSs) was limited in water medium. The present study also revealed that the self-microemulsified drug delivery system of poorly-water soluble drugs exemplified by fenofibrate increased their dissolution rate leading to enhance their bioavailability correspondingly. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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