School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, United Kingdom; Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston PR1 2HE, United Kingdom; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom.
Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston PR1 2HE, United Kingdom; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom.
Int J Pharm. 2018 Mar 1;538(1-2):250-262. doi: 10.1016/j.ijpharm.2017.12.049. Epub 2018 Jan 12.
Proliposome powders were prepared via a slurry method using sorbitol or D-mannitol as carbohydrate carriers in 1:10 or 1:15 w/w lipid phase to carrier ratios. Soya phosphatidylcholine (SPC) and cholesterol were employed as a lipid phase and Beclometasone dipropionate (BDP) was incorporated as a model drug. Direct compaction using a Minipress was applied on the lipid-enriched powder in order to manufacture proliposome tablets. Sorbitol-based proliposome tablets in a 1:15 w/w ratio were found to be the best formulation as it exhibited excellent powder flowability with an angle of repose of 25.62 ± 1.08°, and when compacted the resultant tablets had low friability (0.20 ± 0.03%), appropriate hardness (crushing strength) (120.67 ± 12.04 N), short disintegration time (5.85 ± 0.66 min), and appropriate weight uniformity. Moreover, upon hydration into liposomes, the entrapment efficiency for sorbitol formulations in both 1:10 and 1:15 lipid to carrier ratios were significantly higher (53.82 ± 6.42% and 57.43 ± 9.12%) than D-mannitol formulations (39.90 ± 4.30% and 35.22 ± 6.50%), respectively. Extended stability testing was conducted for 18 months, at three different temperature conditions (Fridge Temperature (FT; 6 °C), Room Temperature (RT; 22 °C) and High Temperature (HT; 40 °C)) for sorbitol-based proliposome tablets (1:15 w/w ratio). Volume median diameter (VMD) and zeta potential significantly changed from 5.90 ± 0.70 µm to 14.79 ± 0.79 µm and from -3.08 ± 0.26 mV to -11.97 ± 0.26 mV respectively at month 18, when samples were stored under HT conditions. Moreover, the entrapment efficiency of BDP decreased from 57.43 ± 9.12% to 17.93 ± 5.37% following 18 months storage under HT conditions. Overall, in this study for the first time, proliposome tablets were manufactured and thoroughly characterized, and sorbitol showed to be a promising carrier.
采用 1:10 或 1:15（w/w）脂质相与载体的比例，通过浆法制得前体脂质体粉末，其中山梨糖醇或 D-甘露醇用作碳水化合物载体。使用大豆卵磷脂（SPC）和胆固醇作为脂质相，并掺入倍氯米松二丙酸酯（BDP）作为模型药物。使用 Minipress 对富含脂质的粉末直接进行压缩，以制造前体脂质体片剂。发现基于山梨糖醇的前体脂质体片剂在 1:15（w/w）的比例下是最佳配方，因为它表现出极好的粉末流动性，休止角为 25.62±1.08°，并且当压缩时，所得片剂的易碎性（0.20±0.03%）低、硬度（压碎强度）（120.67±12.04N）适中、崩解时间短（5.85±0.66min）、重量均匀度适当。此外，在水合形成脂质体后，1:10 和 1:15 脂质与载体的比例的山梨糖醇制剂的包封效率显著更高（分别为 53.82±6.42%和 57.43±9.12%），而 D-甘露醇制剂的包封效率（分别为 39.90±4.30%和 35.22±6.50%）。在三种不同温度条件（冰箱温度（FT；6°C）、室温（RT；22°C）和高温（HT；40°C））下，对基于山梨糖醇的前体脂质体片剂（1:15（w/w）比例）进行了 18 个月的扩展稳定性测试。体积中值直径（VMD）和 Zeta 电位分别从 5.90±0.70µm 显著变化至 14.79±0.79µm 和从-3.08±0.26mV 显著变化至-11.97±0.26mV，在 18 个月时，样品在 HT 条件下储存。此外，在 HT 条件下储存 18 个月后，BDP 的包封效率从 57.43±9.12%降低至 17.93±5.37%。总的来说，在这项研究中，首次制造并彻底表征了前体脂质体片剂，并且山梨糖醇显示出是一种有前途的载体。
