School of Pharmacy and Medical Sciences, University of South Australia, City East Campus, Adelaide, South Australia 5001, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science & Technology, Australia.
School of Pharmacy and Medical Sciences, University of South Australia, City East Campus, Adelaide, South Australia 5001, Australia.
Eur J Pharm Biopharm. 2018 Apr;125:13-20. doi: 10.1016/j.ejpb.2017.12.012. Epub 2017 Dec 22.
The method of supersaturation for achieving high drug loads in lipid-based formulations is under exploited and relatively unexplored, especially in the case of solid-state lipid-based formulations. Silica-lipid hybrids are solid-state lipid-based formulations designed for improving the oral delivery of poorly water-soluble drugs. However, their application to compounds of low potency and requiring large doses is limited by their low drug loading capacity. Here, an innovative technique to fabricate supersaturated silica-lipid hybrid formulations (super-SLH) has been established and the relationship between drug load and performance investigated. Using the model poorly water-soluble drug, ibuprofen, super-SLH was fabricated possessing drug loads ranging from 8 to 44% w/w, i.e. greater than the previously developed standard ibuprofen silica-lipid hybrids (5.6% w/w). Drug crystallinity of the encapsulated ibuprofen ranged from non-crystalline to part-crystalline with an increase in drug load. Super-SLH achieved improved rates and extents of dissolution when compared to pure ibuprofen, regardless of the drug load. The percentage increase in dissolution extent at 60 min varied from 200 to 600%. The results of the current study indicate that supersaturation greatly improves drug loading and that 16-25% w/w is the optimum loading level which retains optimal dissolution behaviour for the oral delivery of ibuprofen, which has the potential to be translated to other poorly water-soluble drugs.
用于实现脂质体制剂中高药物负载的过饱和方法尚未得到充分利用，也相对没有得到充分探索，尤其是在固态脂质体制剂的情况下。硅脂质混合体是为改善难溶性药物的口服递送而设计的固态脂质体制剂。然而，由于其载药量低，它们在应用于低效力和需要大剂量的化合物方面受到限制。在这里，建立了一种用于制备过饱和硅脂质混合体制剂（超 SLH）的创新技术，并研究了药物负载与性能之间的关系。使用模型难溶性药物布洛芬，制备了具有 8-44%w/w 药物负载的超 SLH，即大于以前开发的标准布洛芬硅脂质混合体（5.6%w/w）。包封的布洛芬的药物结晶度从非晶态到部分晶态随药物负载的增加而增加。与纯布洛芬相比，超 SLH 无论药物负载如何，都能提高溶解速率和程度。在 60 分钟时，溶解程度的百分比增加从 200%到 600%不等。当前研究的结果表明，过饱和度大大提高了药物负载，并且 16-25%w/w 是最佳负载水平，可保持布洛芬口服递送的最佳溶解行为，这有可能转化为其他难溶性药物。
