Development of vitamin B12 containing pullulan-bovine serum albumin microparticles designed dry powder inhaler: In-vitro and in-vivo study

Abstract

The poor permeability and low bioavailability of vitamin B12 (vit. B12) through the mucosal lining of lungs are required substitutes. Therefore, the present work aims to develop a dry powder inhaler (DPI) of (Vit.B12) encapsulated into bovine serum albumin (BSA) followed by pullulan coated micro particles (Vit.B12-Pull-BSA) through spray drying. Briefly, pullulan was used as a mucoadhesive agent whereas BSA was used as an encapsulating agent. The obtained Vit.B12-Pull-BSA micro-particles were characterized using different in-vitro spectroscopic techniques, in vitro dissolution, mucoadhesion study, particle size analysis, etc. As a result, the surface morphology of Vit.B12-Pull-BSA micro-particles shows spherical micro-particle with circular surface morphology that can be suitable for pulmonary drug delivery. The PXRD study reveals the conversion of the crystalline nature of vitamin B12 to amorphous nature. Particle size showed 590.1 nm and zeta potential of microparticles was −27.3 mV respectively, which indicates the good stability of particles. The in-vitro assessment of Vit.B12-Pull-BSA microparticles using cascade Impactor revealed that 90.8 ± 1.1% of dry powder formulation was emitted from the device whereas 64.1 ± 6.8% of vitamin B12 loaded particles were reached at a fine stage that suggests preferential delivery of micro-particle. Male Wister rats were utilized for pharmacokinetic analysis through intratracheal administration of Vit.B12-Pull-BSA micro-particles that confirmed the increase in the permeability. Accordingly, it increases the 4.5 folds' relative bioavailability of vitamin B12. In conclusion, the Vit.B12-Pull-BSA micro-particles-based DPI offers improved permeability and bioavailability that can provide the alternative for conventional drug delivery.