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.

A Facile and Novel Approach to Manufacture Paclitaxel-Loaded Proliposome Tablet Formulations of Micro or Nano Vesicles for Nebulization

“…Being structurally similar to biological membranes, unlike polyoxyethylated castor oil, are not associated with hypersensitivity reactions (15,16). Hydrophobic compounds are commonly entrapped within the concentric bilayers of the vesicles, whereas hydrophilic molecules position into the central aqueous core (17). A number of studies have demonstrated that PTX can be entrapped into liposomes bilayers without PEGylation (18)(19)(20)(21)(22).…”

“…However, a notable limitation of liposomes however is poor stability upon storage (31)(32)(33) exhibited by aggregation or fusion of vesicles and drug leakage from the vesicles (17,34). The formulation of liposomes in a dry-stable form referred to as proliposomes (which may be hydrated with water to generate liposomes) has been developed as a solution to stability issues associated with the vesicles (35,36).…”

Spontaneous In Situ Formation of Liposomes from Inert Porous Microparticles for Oral Drug Delivery

“…In 1986, Payne et al [ 24 ] introduced dry and free-flowing liposomal formulations that could produce multi-lamellar liposomes upon hydration. These systems were given the name “proliposomal formulations” and have been a subject of various studies [ 5 , 25 , 26 , 27 , 28 , 29 ].…”

<p>Proliposomes for oral delivery of total biflavonoids extract from <em>Selaginella doederleinii</em>: formulation development, optimization, and in vitro–in vivo characterization</p>

“…However, despite liposomes enable an antitumor agent to improve solubility and bioavailability, inherent limitation such as aggregation, drug leakage, sedimentation, phospholipid susceptibility to oxidation and hydrolysis still exist 26,27. In order to overcome these issues, a proliposome formulation, dry and free-flowing granular powder, which can disperse to form liposomes suspension via addition of water, is adopted in the current study 28…”