Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 N. Eagleville Rd, Storrs, Connecticut, 06269-3092, USA.
Drug Product Development, Research and Development, AbbVie Inc., North Chicago, Illinois, 60064, USA.
AAPS PharmSciTech. 2018 Oct;19(7):3298-3310. doi: 10.1208/s12249-018-1178-x. Epub 2018 Sep 14.
FDA-approved self-emulsifying medicines rely on liquid-based formulations, which can exhibit limited stability and short shelf-lives. Solid self-emulsifying drug delivery systems (SEDDS) can improve such issues, but there is still a great need for identifying suitable porous carriers to convert liquid SEDDS into solids without impairing their mechanical properties, functionality, and industrial feasibility. The impact of SEDDS adsorption on tableting is also poorly understood. Therefore, solid SEDDS were prepared by adsorbing liquid SEDDS onto ten commercially available porous excipients. Products were assessed with respect to mechanical behavior, tabletability, and product performance. Adsorbing SEDDS onto porous excipients led to satisfactory stability, with the exception of Zeopharm® 600 due to its high alkalinity, and Neusilin® US2/UFL2, which caused quercetin to crystallize out of the liquid concentrate. SEDDS adsorption reduced the elastic recovery of most excipients, making tableting achievable using Aeroperl® 300 and Aerosil® 200/300. The impact of SEDDS on elastic recovery provides additional understanding on solid SEDDS manufacture process. Acceptable tablets were made via direct compression but with slow disintegration. Addition of a superdisintegrant (crospovidone 5% w/w) ensured tablet manufacturing without impairment of product performance. Solid SEDDS displayed several technical advantages over their liquid counterparts, but attention must be given to the properties of the porous excipient chosen. Drug-excipient interactions play a significant role in drug degradation and crystallization in solid SEDDS. Improved mechanical behavior upon adsorption led to well-composed tablets that performed satisfactorily in vitro upon addition of a superdisintegrant. This study provides an insight on excipient-oriented rational development of solid SEDDS.
美国食品和药物管理局批准的自乳化药物依赖于基于液体的制剂，其稳定性和保质期有限。固体自乳化药物递送系统（SEDDS）可以改善这些问题，但仍需要确定合适的多孔载体，将液体 SEDDS 转化为固体，而不损害其机械性能、功能和工业可行性。SEDDS 吸附对压片的影响也知之甚少。因此，通过将液体 SEDDS 吸附到十种市售的多孔赋形剂上来制备固体 SEDDS。产品的机械性能、可压性和产品性能方面进行了评估。将 SEDDS 吸附到多孔赋形剂上导致稳定性令人满意，除了 Zeopharm® 600 由于其高碱性和 Neusilin® US2/UFL2 导致槲皮素从液体浓缩物中结晶出来之外。SEDDS 吸附降低了大多数赋形剂的弹性恢复，使得使用 Aeroperl® 300 和 Aerosil® 200/300 可以实现压片。SEDDS 对弹性恢复的影响提供了对固体 SEDDS 制造工艺的更多理解。通过直接压缩可以制成可接受的片剂，但崩解速度较慢。添加超崩解剂（交联聚维酮 5%w/w）可确保在不损害产品性能的情况下制造片剂。固体 SEDDS 相对于其液体对应物具有许多技术优势，但必须注意所选择的多孔赋形剂的性质。药物-赋形剂相互作用在固体 SEDDS 中的药物降解和结晶中起着重要作用。吸附后机械性能的改善导致组成良好的片剂，在添加超崩解剂后在体外表现出令人满意的性能。本研究为基于赋形剂的固体 SEDDS 合理开发提供了深入了解。
