| Aryl propionic acid derivatives in non-steroidal drugs (flurbiprofen, ketoprofen, ibuprofen, loxoprofen, naproxen, etc.) have anti-inflamatory, antifebrile and analgesic actions which have been using in arthritis, rheumatoid arthritis and chronic pains. However, many patients suffer from gastro-intestinal disturbance when these drugs are administered orally, which limits the application of them. When the active ingredients are delivered transdermally, the topical concentration of them in joint location can increase; gastro intestinal disturbance may be avoided; furthermore, the active ingredients are continuously released at a constant rate. Therefore, much attention has been given to the transdermal delivery system (TDS) of these drugs.The high performance liquid chromatographic (HPLC) method using a reversed-phase column was adopted for determination of flurbiprofen (FP), ketoprofen (KP), ibuprofen (IP), loxoprofen (LP) and naproxen (NP). The relation between the permeation of these drugs through excised rat skin and oil-water partition coefficient was investigated. The cumulative penetrating amount and steady state flux of KP and FP increased when the polarity of alcoholic solvents decreased from n-butyl alcohol to n-octyl alcohol, which indicated that KP and FP in nonpolar polymers can maximize their thermodynamic activity and further increase the skin permeability. It was tested by the comparison of the drug release behavior through excised nude mouse skin between the transdermal delivery system of FP (FP-TDS) with polyisobutylene and FP-patch with hydrophilic matrix. Orthogonal design was used to optimize the composition of FP-TDS. Then, step-by-step, different content of drugs, antioxidants and permeation enhancers were chosen in FP-TDS. The FP released from FP-TDS at zero-order through excised nude mouse skin and the cumulative penetrating percentage of FP amounted to 85%. The differential scanning calorimetry (DSC) showed that 8.1% azone in preparation can make the minicrystal of FP disappear and form solid sols. For the first time, electret was used as substrate layer in FP-TDS. The matrix of FP-TDS can administer to the stability of electret, and electrostatic field of electret can enhance permeation of FP (1.61±0.33 times) .The content of FP in FP-TDS was measured by spectrophotometric at 247nm after abstracted with PBS (pH7.4) from medical gasoline. FP in dissolution medium was measured by spectrophotometric, too. In 40℃ and relative humidity 75%, the content of FP in FP-TDS and release of FP from FP-TDS kept stable for three months.FP in plasma of rabbit was measured by HPLC method with KP as an internal standard. The fever was induced by subcutaneous injection of yeast suspention (10%.W/V) 3 mL.Kg-1 and endotoxin (2 μg.mL-1) 0.2 mL.Kg-1. After FP-TDS and FP suspension (25 mg.Kg-1) was administred to rabbit respectively, the inhibition rate (E, %) of rabbit fever and FP in plasma were found correlative and the inhibition rates (E, %) of rabbit fever which administred FP-TDS were placid and persistent. By measuring the content of FP in FP-TDS after administration, it was tested that 58.20%±6.66% FP in FP-TDS was penetrated. Cmax were much lower after a single application of FP-TDS than after FP suspension (mean±SD: 7.11±2.57 μg.mL-1 versus 168.72±23.76 μg.mL-1 respectively), and the mean MRT prolonged (11.87 h±0.79 h and 3.19 h±0.99 h respectively). The mean relative bioavailability of FP from FP-TDS was 48.12%.
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