Development of delayed-release proliposomes tablets for oral protein drug delivery

One among many attempts to improve oral protein drug delivery was utilizing the colloidal drug carriers particularly liposomes.

The purpose was to develop proliposomes of bovine serum albumin (BSA) in the form of granules and delayed-release tablets by using simple tablet manufacturing process.

BSA proliposomes granules were prepared by spraying 7:3 (w/w) -- lecithin:cholesterol solution mixture onto BSA-mannitol granules rotating in a glass coating pan. BSA proliposomes granules were directly compressed into tablets and subsequently coated with Eudragit(®) L100 film. The physical properties and stability in gastrointestinal fluids of delayed-release BSA proliposomes tablets as well as reconstituted liposomes were assessed.

The BSA proliposomes tablets disintegrated readily and the obtained reconstituted BSA liposomes exhibited multilamellar vesicles, the size and entrapment efficiency of which were around 2--3 µm and 10--14%, respectively. The delayed-release BSA proliposomes tablets were found to be relatively stable in United States Pharmacopoeia (USP) simulated gastric and intestinal fluids. Increase in amount of BSA in granules resulted in the increase in entrapment efficiency and loading capacity.

The Fourier transform infrared spectroscopy (FTIR) results indicated increase in α-helix structure of BSA entrapped in liposomes. ³¹P phosphorous nuclear magnetic resonance spectroscopy (³¹P-NMR) spectrum indicated interaction between BSA molecules and phosphoric acid polar groups of bilayers membrane.

The delayed-release BSA proliposomes tablets developed could completely be reconstituted into liposomes with sufficient resistance to the hostile environment in gastrointestinal tract.