Proliposome Tablets Manufactured Using A Slurry-Driven Lipid-Enriched Powders: Development, Characterization and Stability Evaluation

Abstract

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. [Abstract copyright: Copyright © 2017. Published by Elsevier B.V.]