| Summary: | 碩士 === 台北醫學院 === 藥學研究所 === 87 === It is well established that the rate-determining step in the absorption process for poorly water-soluble drugs is the dissolution rate for such drugs in the gastrointestinal fluids rather than the rapidity of their diffusion across the gut wall. Thus, the increase of the dissolution rate by increasing the solubility of poorly water-soluble drugs will improve the absorption rate. In this study, solid dispersions of nifedipine (m.p. 173oC) prepared with two water-soluble carrier systems, Gelucire 44/14 / PEG 600 and PVP/PEG 6000, by fusion method was developed to increase the solubility of nifedipine, then increasing the dissolution rate. The system of Gelucire 44/14 and PEG 600 was made by two methods. The first one was to melt the carriers at its melting point before evenly distributing nifedipine into it. The other one was to mix the carriers and nifedipine before melting them together at a higher temperature that both drug and carrier could melt. In the beginning, DSC analysis of the depression of melting point and the inhibition of crystallization of nifedipine by carriers was carried out. The results showed that Gelucire 44/14 and PEG 6000 inhibited the crystallization of nifedipine after melting them at a higher temperature over the ratio of 50% (w/w) and 60% (w/w), respectively. PVP could express the same effects at all ratios. The formation of amorphous state of nifedipine as a result of crystallization inhibition also increased with increasing ratio of carriers. Besides, mixing PEG 6000 with nifedipine at the ratio of 3:1, the melting point of nifedipine was decreased to approximately 110oC. This certainly would make the preparations of solid dispersion by fusion method more practically acceptable. Dissolution tests further demonstrated that nifedipine that fused with these carriers had a higher dissolution rate than that unmodified. For Gelucire 44/14 and PEG 600 system, the dissolution rate from those prepared at a higher temperature was faster than that prepared just at the melting point of Gelucire. The dissolution rate increased with increasing amount of Gelucire 44/14 as well. For the PEG 6000 and PVP series system, the results showed that the higher amount of PEG 6000 and PVP, the faster of the dissolution rate of nifedipine would become; The higher the molecular weight of PVP, the slower of the dissolution rate. Due to the viscous nature, the existence of PEG 6000 and PVP in the preparations would possibly increase the adhesion among particles, which makes them difficult to disperse into water minimizing the surface area available for dissolution. A set of formulation containing a higher amount of both additives (nifedipine : PEG 6000 : PVP K-12 = 1:3:3) was further mixed with Aerosil : Tween 80 = 1:1 to improve the dispersion. The results demonstrated that the dissolution rate became faster.
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