Inclusion complex of cyclodextrin with ergotamine and evaluation of cyclodextrin-based nanosponges

Purpose The anti-migraine drugs show first-pass metabolism, short half-life, and low bioavailability resulting in repeated dose or overdose effect. Polymeric, biodegradable and highly porous nanosponges emerge as a promising carrier for migraine treatment to improve aqueous solubility, stability and bioavailability. Method Ergotamine nanosponges prepared by interfacial polymerization method wherein hydroxypropyl beta-cyclodextrin inclusion complex was crosslinked using toluene diisocyanate. Caffeine used as a permeation enhancer for ergotamine by forming soluble molecular complex with cyclodextrin moiety of nanosponges. Further, nanosponges were characterized for particle size, zeta potential, entrapment efficiency, percentage drug release profile, antioxidant activity, photostability and instrumental analytical studies. Results Caffeine significantly improved the permeation of ergotamine nanosponges. The particle size for optimized nanosponges was 693.5 +/- 11.7 nm, zeta potential of - 19.4 +/- 5.69 mV with high colloidal stability and maximum entrapment efficiency of 98.88 +/- 2.8%. In-vitro and ex-vivo studies exhibited controlled release profiles of ergotamine 81.6% +/- 3.4% and 79% +/- 4.2% for 24 h, respectively. Nanosponges demonstrated higher antioxidant activity 85.68% +/- 1.23% whereas photostability data showed no significant decrease in drug content indicating good stability. Fourier transform infrared spectroscopy confirmed significant interaction of ergotamine with cyclodextrin-based nanosponges. Conclusion Nanosponges showed improvement in bioavailability of ergotamine and long-term stability offering inexpensive, productive and safe alternative for migraine. [GRAPHICS] .