本文關(guān)鍵詞： 馬來(lái)酸阿塞那平 經(jīng)皮給藥 貼劑　出處：《蘇州大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：將馬來(lái)酸阿塞那平制備成經(jīng)皮給藥貼劑，通過(guò)對(duì)其進(jìn)行體外滲透研究、制劑學(xué)研究、制劑質(zhì)量研究和體內(nèi)藥動(dòng)學(xué)研究制備合格的貼劑，以達(dá)到緩控釋藥的目的。 方法：（1）對(duì)馬來(lái)酸阿塞那平進(jìn)行處方前研究。建立馬來(lái)酸阿塞那平含量分析方法，包括標(biāo)準(zhǔn)曲線的繪制，精密度、回收率和穩(wěn)定性的考察；對(duì)馬來(lái)酸阿塞那平的理化性質(zhì)進(jìn)行了考察，包括不同溶劑中的溶解度和油水分配系數(shù)測(cè)定；采用Franz擴(kuò)散池法，對(duì)馬來(lái)酸阿塞那平的體外滲透能力進(jìn)行評(píng)價(jià)；（2）采用溶劑揮發(fā)法制備馬來(lái)酸阿塞那平貼劑，以粘附力、釋放度和滲透量為評(píng)價(jià)指標(biāo)，考察交聯(lián)劑和增塑劑對(duì)貼劑的影響，優(yōu)選最終處方，并對(duì)固化時(shí)間進(jìn)行考察；（3）對(duì)貼劑的質(zhì)量進(jìn)行評(píng)價(jià)，，包括粘附力、釋放度、滲透性和含量均勻度；（4）通過(guò)給予大鼠自制貼劑，初步研究馬來(lái)酸阿塞那平貼劑的體內(nèi)藥動(dòng)學(xué)特征。 結(jié)果：（1）建立的馬來(lái)酸阿塞那平HPLC含量分析方法，標(biāo)準(zhǔn)曲線線性關(guān)系良好，精密度、回收率符合要求，樣品溶液在12h內(nèi)穩(wěn)定。溶解度測(cè)定結(jié)果顯示，馬來(lái)酸阿塞那平在水中的溶解度為6.42±0.48mg/mL，在其它溶劑中溶解度最高的是甲醇，17.90±1.72mg/mL，因此最終處方中加入1mL甲醇來(lái)溶解藥物。馬來(lái)酸阿塞那平的溶解度還顯示出一定的pH依賴性，pH1.2時(shí)，溶解度為9.33±1.22mg/mL，而pH8.0時(shí)，溶解度為2.54±0.26mg/mL；馬來(lái)酸阿塞那平的油水分配系數(shù)LogP值為-0.95，有一定的親水性。體外滲透結(jié)果表明，馬來(lái)酸阿塞那平滲透速率隨著濃度增大而增大，當(dāng)濃度達(dá)到5mg/mL時(shí)，滲透系數(shù)達(dá)到49.55μg/cm2h，24h累積透過(guò)量達(dá)到1.3mg，透過(guò)百分率也達(dá)到了61.69%，說(shuō)明馬來(lái)酸阿塞那平具有良好的經(jīng)皮滲透性能。（2）通過(guò)考察各種因素對(duì)貼劑的影響，確定貼劑載藥量為15%，增塑劑TEC用量為9.5%，交聯(lián)劑琥珀酸用量為0.5%，固化時(shí)間為1h。通過(guò)不同方程擬合，確定藥物從該貼劑中的釋放符合higuchi方程，其釋放機(jī)制為擴(kuò)散和溶蝕的雙重作用。（3）三批貼劑進(jìn)行質(zhì)量評(píng)價(jià)結(jié)果顯示，貼劑粘附力大于14，持粘力大于75h；24h累積釋放量大于350μg/cm2，釋放百分比大于14%；滲透量大于280μg/cm2，滲透百分比大于11%；貼劑含量均勻度符合《中國(guó)藥典》相關(guān)要求。（4）大鼠體內(nèi)藥代動(dòng)力學(xué)試驗(yàn)結(jié)果表明，自制馬來(lái)酸阿塞那平貼劑具有明顯的緩釋效果。 結(jié)論：成功制備了具有緩釋效果的馬來(lái)酸阿塞那平貼劑，該制劑未見(jiàn)國(guó)內(nèi)外文獻(xiàn)和專利報(bào)道，為的后續(xù)研究打下基礎(chǔ)。
[Abstract]:Objective: to prepare a transdermal patch of Asenapine maleate, and to prepare a qualified patch through in vitro permeation study, preparation study, preparation quality study and in vivo pharmacokinetic study. In order to achieve the purpose of slow and controlled release of drugs. Methods the analepine maleate content analysis method was established, including the drawing of standard curve, precision, recovery and stability. The physicochemical properties of Asenapine maleate were investigated, including the determination of solubility and oil-water partition coefficient in different solvents. The in vitro osmotic capacity of azenapine maleate was evaluated by Franz diffusion cell method. (2) Asena maleate patch was prepared by solvent volatilization method. The influence of crosslinking agent and plasticizer on the patch was investigated with adhesion, release and permeation as the evaluation index, and the final prescription was selected. The curing time was investigated. Evaluation of the quality of the patch, including adhesion, release, permeability and content uniformity; (4) the pharmacokinetic characteristics of Asenapine maleate patch were studied. Results the standard curve was linear, the precision and the recovery rate were satisfied with the standard curve established for the determination of HPLC content of atenapine maleate. The sample solution was stable within 12 hours, and the solubility of azenapine maleate in water was 6.42 鹵0.48 mg / mL, and the highest solubility in other solvents was methanol. 17. 90 鹵1. 72 mg / mL, so 1 mL methanol was added to the final prescription to dissolve the drug. The solubility of Asenapine maleate also showed a certain pH dependence at pH 1.2. The solubility was 9.33 鹵1.22 mg / mL, while in pH8.0, the solubility was 2.54 鹵0.26 mg / mL; The oil and water partition coefficient (LogP) of Asenapine maleate was -0.95, and it had hydrophilicity. The osmotic rate of Asenapine maleate increased with the increase of concentration in vitro. When the concentration reached 5 mg / mL, the permeation coefficient reached 49.55 渭 g / cm ~ (-2) h ~ (-1) and the cumulative transmittance reached 1.3 mg / mL, and the permeation percentage reached 61.69%. The results showed that Asenapine maleate had good transdermal permeability. (2) by examining the effect of various factors on the patch, the dosage of the patch was 15 and the amount of plasticizer TEC was 9.5%. The dosage of crosslinking agent succinic acid was 0.5 and the curing time was 1 h. By different equation fitting, the release of the drug from the patch was confirmed to be in accordance with the higuchi equation. The mechanism of release is diffusion and dissolution. The quality evaluation of three batches of patch shows that the adhesive force of the patch is more than 14 and the adhesive force is more than 75 h. The cumulative release amount was more than 350 渭 g / cm ~ 2 and the release percentage was more than 14 渭 g / cm ~ 2. The osmotic capacity was more than 280 渭 g / cm ~ 2, and the osmotic percentage was more than 11 渭 g / cm ~ 2. The results of pharmacokinetic test in rats showed that the self-made Asenapine maleate patch had obvious sustained release effect. Conclusion: Asenapine maleate patch with sustained release effect has been successfully prepared, which has not been reported in domestic and foreign literatures and patents, which lays a foundation for further study.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R943

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