DRUG PARTICLE-SIZE REDUCTION FOR DECREASING GASTRIC IRRITANCY AND ENHANCING ABSORPTION OF NAPROXEN IN RATS
DRUG PARTICLE-SIZE REDUCTION FOR DECREASING GASTRIC IRRITANCY AND ENHANCING ABSORPTION OF NAPROXEN IN RATS
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DOI：
10.1016/0378-5173(95)00148-c
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发表时间：
1995-10-31
影响因子：
5.8
通讯作者：
CONZENTINO, P
中科院分区：
文献类型：
--
作者：
LIVERSIDGE, GG;CONZENTINO, P
胃粘膜损伤是口服NSAIDs后最常见的事件，是由于全身效应和高局部药物浓度效应的共同作用。大鼠口服萘普生后，通过将药物颗粒从20-30微米减小到270 nm，并用Pluronic F-68稳定混悬液中的颗粒，从而减少了对胃的刺激。刺激性的减少归因于局部高浓度和长期浓度的降低，可归因于晶体尺寸的减小。此外，口服纳米粒制剂观察到的刺激量与静脉注射萘普生相似。萘普生的尺寸减小也与吸收速率明显增加约有关。4倍。吸收速率的增加归因于纳米晶体配方溶解表面积的增加。
Gastric mucosal damage, the most common event following oral administration of NSAIDs, is due to a combination of a systemic effect and a high local drug concentration effect. It has been demonstrated in rats that the gastric irritation induced following oral administration of naproxen was decreased by reducing drug particle size from 20-30 mu m to 270 nm and stabilizing the particles in suspension with pluronic F-68. The reduction in irritation is attributed to a decrease in the local high and prolonged concentration of naproxen attributable to reduced crystal size. Further the amount of irritation observed with the orally administered nanoparticle formulation is similar to that following intravenous administration of naproxen. The size reduction of naproxen was also associated with an apparent increase in the rate of absorption by approx. 4-fold. The increase in the rate of absorption is attributed to an increase in surface area for dissolution for the NanoCrystal formulation.