| Ketoprofen Self-Emulsifying Drug Delivery System, choosing ketoprofen as the drug and oils and surfactants as vehicles, was thermodynamically stable SEDDS. Ketoprofen (KP), a nonsteroidal anti-inflammatory and analgesic drug, has been mainly used for rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute gout and other acute pains. Most oral dosage forms of KP had low bioavailability because KP could hardly dissolve in water. Therefore, SEDDS was selected as the carrier to prepare KPSEDDS capsule to increase dissolution, promote absorption and enhance bioavailability of KP.The solubility of KP in Ethyl Oleate and Labrafac CC, which was higher than other choosed oils, was 23.19±2.58 and 29.46±2.91 mg·ml-1 respectively. KP, the logarithm of apparent partition coefficients in octanol/0.1 mol·L-1 HCl, octanol/water and octanol/pH 6.8 PBS were 2.94,2.43 and 0.96 respectively, was lipophilic. Two methods, UV spectrophotometry and HPLC, were developed for in vitro assay. HPLC could eliminate the disturbance of excipients on analysis.Ethyl oleate and Labrafac CC were used for oils. Two kinds of systems were made sure through the investigation of the required HLB of Ethyl oleate and Labrafac CC, compatible combination between various surfactants and oils and the cosolvent ability of increasing solubility of the surfactants, which were ethyl oleate, Tween80, Transcutol and Labrafac CC, T70S30(70%Tween80,30%Span80), Transcutol respectively. The pseudo-ternary phase diagrams of two kinds of systems were studied, the results of which indicated that the self-emulsifying region area was reduced by 50% and 15.8% and the maximum of emulsified oils was 40% and 55% (w). We investigated the effects of the vehicle contents, temperature, the flow shape, pH and volume of media on the self-emulsifying efficiency. All results brought us a best KPSEDDS formulation.The results from drug release mechanism were consistent with Hixson-Crowell equation by bulk- equilibrium reverse dialysis bag technique.The physicochemical properties of blank SEDDS and KPSEDDS were studied. Their viscosities were 5.57 ×10-2 and 6.49 × 10-2 Pa·s, indicating KP loading can increase the... |
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