Dorkoosh Farid A, Verhoef J Coos, Verheijden Jos H M, Rafiee-Tehrani Morteza, Borchard Gerrit, Junginger Hans E
Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
Pharm Res. 2002 Oct;19(10):1532-6. doi: 10.1023/a:1020416918624.
The aim of this study was to investigate the enhancement of peroral octreotide absorption using delivery systems based on superporous hydrogel (SPH) and SPH composite (SPHC) polymers.
Six female pigs (BW of 23.5 kg) were used in this study. SPH-based delivery systems were made of two components: 1) a conveyor system made of SPH and SPHC; 2) a core that contained octreotide. The core was inserted into the conveyor system (core inside, c.i.) or attached to the surface of the conveyor system (core outside, c.o.). Four different peroral formulations were investigated: c.i., c.o., core outside including trimethyl chitosan chloride (c.o.t.), and octreotide only in the absence of any polymer (o.o.). All formulations were placed in enteric-coated gelatin capsules (size 000) and administered perorally. Intravenous administration was used to determine bioavailability (F) values. Blood samples taken from the cannulated jugular vein were analyzed by radioimmunoassay.
Peroral administration of 15 mg o.o. resulted in low F values of 1.0 +/- 0.6% (mean +/- SEM) whereas c.i. and c.o. administrations resulted in remarkably higher F values of 12.7 +/- 3.6% and 8.7 +/- 2.4%, respectively. By the addition of trimethyl chitosan chloride as an extra absorption enhancer to c.o.t., the highest bioavailability (16.1 +/- 3.3%) was achieved.
These novel delivery systems based on SPH and SPHC polymers are able to increase the peroral bioavailability of octreotide by mechanical fixation and increasing the retention of the dosage form at the absorption site.
本研究旨在探讨基于超多孔水凝胶（SPH）和SPH复合材料（SPHC）聚合物的给药系统对口服奥曲肽吸收的增强作用。
本研究使用了6只体重为23.5千克的雌性猪。基于SPH的给药系统由两部分组成：1）由SPH和SPHC制成的输送系统；2）含有奥曲肽的核心部分。核心部分插入输送系统内部（核心在内，c.i.）或附着在输送系统表面（核心在外，c.o.）。研究了四种不同的口服制剂：c.i.、c.o.、含氯化三甲基壳聚糖的核心在外（c.o.t.）以及仅不含任何聚合物的奥曲肽（o.o.）。所有制剂均置于肠溶明胶胶囊（000号）中口服给药。通过静脉给药来确定生物利用度（F）值。通过放射免疫分析法对从颈静脉插管采集的血样进行分析。
口服15毫克o.o.导致较低的F值，为1.0±0.6%（平均值±标准误），而c.i.和c.o.给药的F值分别显著更高，为12.7±3.6%和8.7±2.4%。通过向c.o.t.中添加氯化三甲基壳聚糖作为额外的吸收增强剂，实现了最高的生物利用度（16.1±3.3%）。
这些基于SPH和SPHC聚合物的新型给药系统能够通过机械固定和增加剂型在吸收部位的滞留来提高奥曲肽的口服生物利用度。
