Pohja Seppo, Suihko Eero, Vidgren Mika, Paronen Petteri, Ketolainen Jarkko
Department of Pharmaceutics, University of Kuopio, POBox 1627, FIN-70211 Kuopio, Finland.
J Control Release. 2004 Feb 10;94(2-3):293-302. doi: 10.1016/j.jconrel.2003.09.017.
The aim of this study was to investigate the effect of a high degree on substitution (DS) on starch acetate (SA) and SA concentration on tablet properties. SAs with a DS of 2.6 and 3.0 were used as matrix formers with propranolol hydrochloride (PH) as a model drug. The SA-3.0 powder had better compactibility than the SA-2.6 powder. A decrease in SA concentration decreased compactibility of PH/SA blended powders when compared to neat SA powders. In general, drug release was considerably slower from SA-3.0 matrices than from SA-2.6 matrices. Also, a decrease in SA concentration increased the drug release rate. Water penetration into 80% (w/w) SA-3.0 matrices was incomplete during 24-h dissolution tests. Diffusion path length increased with time and PH was released by Fickian diffusion. However, all other PH/SA tablets were completely hydrated during dissolution tests. Macroscopic cracks were formed during dissolution, which increased area available for Fickian diffusion and resulted in slow attenuation of the drug release rate. Crack formation, not been reported earlier, must be taken into account in order to understand drug release from SA matrices.
本研究的目的是研究高取代度(DS)的醋酸淀粉酯(SA)以及SA浓度对片剂性质的影响。以DS为2.6和3.0的SA作为骨架材料,盐酸普萘洛尔(PH)作为模型药物。SA-3.0粉末的可压性优于SA-2.6粉末。与纯SA粉末相比,SA浓度降低会降低PH/SA混合粉末的可压性。一般来说,SA-3.0骨架的药物释放比SA-2.6骨架慢得多。此外,SA浓度降低会提高药物释放速率。在24小时溶出试验中,水渗入80%(w/w)的SA-3.0骨架并不完全。扩散路径长度随时间增加,PH通过菲克扩散释放。然而,在溶出试验期间,所有其他PH/SA片剂都完全水合。溶出过程中形成了宏观裂缝,这增加了菲克扩散的可用面积,并导致药物释放速率缓慢衰减。为了理解SA骨架的药物释放,必须考虑此前未报道过的裂缝形成。