Li Ning, Kommireddy Dinesh S, Lvov Yuri, Liebenberg Wilna, Tiedt Louwrens R, De Villiers Melgardt M
School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA.
J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):3252-60. doi: 10.1166/jnn.2006.421.
The results of this study report the novel use of electrostatic layer-by-layer nanoassembly of biocompatible nanoparticulate TiO2 multilayers to coat irregular nifedipine (NF) microcrystals to increase the photostability of the drug when exposed to simulated sunlight and to increase the dissolution rate and possibly the bioavailability of the drug after oral administration. The photostability of NF microcrystals (35 microm) coated with multiple bilayers of positively charged PDDA and negatively charged nanosized TiO2 particles (20-25 nm) was measured when exposed to an illuminance of 12 W/m2 corresponding to a light dose of 30 k lux or 25 W/m2 corresponding to light dose of 60 k lux. The dissolution rate of nifedipine from the coated microcrystals was measured in simulated gastric fluid containing 0.05% w/v polysorbate 80. Coating with one TiO2 layer increased the shelf life of nifedipine by 30 hours independent of the intensity of the light exposure. With an increase in the number of TiO2 layers; the photostability of the drug was enhanced even more. A TiO2 monolayer decreased the contact angle by 20 degrees for water and 33 degrees for the dissolution medium as compared with uncoated NF surfaces. This increase in wettability due to a decrease in contact angle increased the dissolution rate of nifedipine microcrystals coated with 1 PDDA/TiO2 bilayer 13-fold after 10 minutes, 5-fold after 1 hour, and 2-fold after 12 hours when compared to uncoated microcrystals. It is assumed that TiO2 increased the photostability because the nanoparticulate multilayers acts as a potential filter protecting the drug from damaging light rays reaching the drug crystals. The dissolution rate was increased because the hydrophilic TiO2 nanoparticles increased the aqueous wettability of the drug crystals thereby preventing aggregation in the dissolution medium. This ensured that the maximum drug surface area was exposed to the dissolution medium.
本研究结果报告了一种新型用途，即利用生物相容性纳米颗粒TiO₂多层膜的静电逐层纳米组装技术，包覆不规则的硝苯地平（NF）微晶，以提高药物在模拟阳光下的光稳定性，并提高口服给药后药物的溶解速率以及可能的生物利用度。当暴露于照度为12 W/m²（对应光剂量为30 klux）或25 W/m²（对应光剂量为60 klux）的光照下时，测量了用带正电荷的聚二烯丙基二甲基氯化铵（PDDA）和带负电荷的纳米级TiO₂颗粒（20 - 25 nm）的多个双层包覆的NF微晶（35微米）的光稳定性。在含有0.05% w/v聚山梨酯80的模拟胃液中测量了包覆微晶中硝苯地平的溶解速率。包覆一层TiO₂可使硝苯地平的保质期延长30小时，且与光照强度无关。随着TiO₂层数的增加，药物的光稳定性进一步增强。与未包覆的NF表面相比，TiO₂单层使水的接触角降低了20度，使溶解介质的接触角降低了33度。由于接触角减小导致的润湿性增加，与未包覆的微晶相比，包覆1个PDDA/TiO₂双层的硝苯地平微晶在10分钟后的溶解速率提高了13倍，1小时后提高了5倍，12小时后提高了2倍。据推测，TiO₂提高了光稳定性，因为纳米颗粒多层膜起到了潜在过滤器的作用，保护药物免受到达药物晶体的有害光线的损害。溶解速率增加是因为亲水性的TiO₂纳米颗粒增加了药物晶体的水相润湿性，从而防止在溶解介质中聚集。这确保了最大的药物表面积暴露于溶解介质中。
