| Tinidazole is usually used to treat trichomonas vaginitis and bacteria vaginitis clinically. But the dosage for oral use is large and there is a lot of adverse effect. Orthodox vaginal praeparatum was eliminated vitro due to the action of clearence of vagina itself. The drug has a short stagnation at site of the action, so curative dose is low and curative time is short. It would influence the therapeutic efficacy. Looking for the pharmaceutical preparation of long stagnation and delayed release is the considerable question for treating vaginitis.Part one The preparation of TNZ microcapsule and research of its quality1. Gelatin and Acacia were used as capsule wall material. TNZ microcapsules were prepared by complex coacervation.2. We established a UV method for the determination of TNZ microcapsules and release rate in vitro. The regression equation is A=0.032C+ 0.0137 (r=0.9999).3. EE and DL were used as index , we investigated different factors that influencing the microencapsulation and obtained the optimal formulation: 5% gelatin solution, 5% acacia solution, quality proportion of capsule core and capsule wall of 1:1, 200rmp angitation, temperature of 50℃, hardening agent of 2mL per 120mL of coacervation system,1h harding time and freeze-drying. The microcapsules prepared by optimal formulation have good appearance, mean diameter was 35.66μm,mean DLwas 34.05%, EE was 74.05% and it sustained released 90% for 240min.Part two The preparation of composite TNZ microcapsules suppository and research of its quality1. we prepared composite TNZ microcapsules suppository by S-40. TNZ composite microcapsules suppository which prepared by hot fusion was content-adqulis, ivory and slick. It has fast-release and delayed-release effect simultaneously.2. The determination was performed on a elite column (ODS, 4.6mm×150mm, 5μm) with methanol-0.01mol·L-1potassium dihydrogen phosphate(15:85) as mobile phase at a flow rate of 1mL·min-1, the detection wavelength was 317nm and column temperature was room temperature. This method is accurate, selective and reproducible.3. 100mL lactic aid solution wae used as the releasing media, the temperature was 37±0.5℃and the rate of rotation was 50r/min. The vitro release of TNZ composite microcapsules suppository followed the first order kinetics : In(1-Mt/M∞)=-0.0051t-0.115 (0.9777), among the total, the fast-release and the delayed-release both followed the Higuchi kinetics, the fast-release(0-180min) the fast-release(0-180min) : Mt/M∞=4.2291t1/2-13.6982(r=0.9960), the delayed-release(180-600min): Mt/M∞=2.6559t1/2 +69.844(r=0.9776).4. TNZ microcapsule suppository was stable under humidity 75%±5% or illumination (4500±500) Lx; stable under temperature (30±2)℃and humidity 65%±5% in six months; stable under temperature (25±2)℃and humidity 60%±10% in twelve months.5. TNZ microcapsule suppository has no irritation and injury to vaginal mucosa after administrate to vagina of rabbits for continuous seven days.There are no literatures and reports internal or overseas about the preparation of TNZ microcapsules by complex coacervation and TNZ microcapsules vaginal suppository prepared in this experiment.
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