Intranasal spanlastics of coenzyme Q10-assisted midazolam nanoformulation for status epilepticus management

To circumvent the blood–brain barrier (BBB), spanlastics was utilized as the drug delivery carrier. The present research focused on development and evaluation of spanlastics via intranasal route to overcome bioavailability issue of Midazolam (MZ). To reduce the oxidative stress in brain during seizures, Coenzyme Q10 (CQ) was used in this study for management of status epilepticus. Midazolam-Coenzyme Q10 loaded spanlastics (MZ-CQ-SPL) were formulated by ethanol injection method followed by optimization with Central composite rotatable design (CCRD). They were then evaluated by performing characterization parameters, in vitro and ex vivo analysis, followed by pharmacodynamic and histopathological studies. Spanlastics demonstrated particle size of 157 nm with high entrapment efficiency (MZ: 80.80 ± 1.66%; CQ: 76.98 ± 1.92%). In vitro release showed sustained release profile (MZ: 91.36 ± 1.26%; CQ: 84.91 ± 1.37%) in 24 h. Ex vivo permeation showed 1.95- and 2.82-times enhanced flux across the nasal mucosa for MZ and CQ, respectively. Pharmacodynamic study revealed enhanced antiepileptic potential of MZ-CQ-SPL in delaying seizure onset along with reducing the severity of seizures. Outcomes concluded the potential of spanlastics in enhancing the bioavailability and therapeutic applicability of MZ and CQ in combination therapy for effective management of seizures.