Interdigitation of lipids for vesosomal formulation of ergotamine tartrate with caffeine: a futuristic trend of intranasal route.

ABSTRACT

OBJECTIVE: This research work aimed to form vesosomes using combination of two drugs ergotamine (ERG) and caffeine for synergistic activity when given intranasally resulting in faster absorption, steric stability, and controlled release. SIGNIFICANCE: The multicompartment vesicles viz., vesosomes of ERG tartrate proved to increase absorption of drugs post-intranasal administration, bypassing the blood-brain barrier via the olfactory pathway. METHODS: The phospholipids like soya lecithin, cholesterol, and dipalmitoyl phosphatidylcholine (DPPC) were used to form a multicompartment structure called vesosomes using ethanol-induced interdigitation of lipids as the preparation method. RESULTS: The formulation showed low particle size (PS) of 315.48 ± 14.27 nm with zeta potential (ZP) of -21.78 ± 4.72 mV, higher % EE of 91.13 ± 1.29%, and controlled release kinetics, when assessed for in-vitro and ex-vivo studies as 97.64 ± 5.13% and 82.25 ± 3.27% release, respectively. Vesosomes displayed several advantages over liposomes like improved stability against phospholipase-induced enzymatic degradation and higher brain uptake 3.41-fold increase of ERG via the olfactory pathway. CONCLUSIONS: The stable vesosomes prepared using interdigitation of saturated phospholipids proved to be a viable option for ERG when administered intranasally for better absorption and bioavailability coupled with ease of administration gaining wider patient acceptance.

Vesosomes as multicompartment vesicles formulated of ergotamine (ERG) and caffeine for synergistic action in migraine treatment.Ethanol induced for interdigitation of lipids in vesosomes preparation exhibited nano-size, good colloidal stability, better encapsulation efficiency, and controlled release profile.ERG vesosomes demonstrated stability against phospholipase-induced enzymatic degradation.