Microemulsion-based drug delivery system for transnasal delivery of Carbamazepine: preliminary brain-targeting study

Abstract

This study reports the development and evaluation of Carbamazepine (CMP)-loaded microemulsions (CMPME) for intranasal delivery in the treatment of epilepsy. The CMPME was prepared by the spontaneous emulsification method and characterized for physicochemical parameters. All formulations were radiolabeled with 99m Tc (technetium) and biodistribution of CMP in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rats was also performed to determine the uptake of the CMP into the brain. CMPME were found crystal clear and stable with average globule size of 34.11 ± 1.41 nm. Tc-labeled CMP solution (CMPS)/CMPME/CMP mucoadhesive microemulsion (CMPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMPMME compared to intravenous CMPME was found to be 2-to 3-fold higher signifying larger extent of distribution of the CMP in brain. Drug targeting efficiency and direct drug transport were found to be highest for CMPMME post-intranasal administration compared to intravenous CMP. Rat brain scintigraphy also demonstrated higher intranasal uptake of the CMP into the brain. This investigation demonstrates a prompt and larger extent of transport of CMP into the brain through intranasal CMPMME, which may prove beneficial for treatment of epilepsy.

Nanosystems in nose-to-brain drug delivery: A review of non-clinical brain targeting studies

“…However, zeta potential is a measure dependent on both particle charge and salt composition of the medium used for particle dilution, and these were not always described. It is often taken as a recommendation that its absolute value should be above 30 mV for maximum stability [15,20,21,38]. A direct electrostatic adsorptive interaction with the mucosa is usually expected with high positive zeta potential values, which justifies that chitosan, a natural cationic polymer, is one of the most mentioned mucoadhesive agents [12,25,39].…”

“…Researchers working on IN delivery frequently cite the disadvantages of classic administration routes, such as those related with the invasiveness of parenteral routes (involving injections); the variable bioavailability, slower onset of action, and low patient compliance of the rectal route; or the unsuitability of the transdermal route in cases of emergency (passive delivery systems) [6][7][8]. In what concerns the oral and oromucosal routes, the limitations are related with altered physiological states of individuals (such as nausea and vomiting, or the hypersalivation and inability to swallow that happen during an epileptic seizure) [3,4,[9][10][11], large intersubject absorption rate variability, slow onset of action, drug-drug and drug-food interactions and cytochrome P450 induction [8,10,[12][13][14][15][16][17]. Moreover, IN delivery offers the possibility of avoiding hepatic first pass metabolism and can reduce drug distribution to non-targeted sites, thereby minimizing systemic adverse effects [8,[18][19][20][21][22][23][24].…”

Development of Carbamazepine Nanostructured Lipid Carrier Loaded Thermosensitive Gel for Intranasal Delivery

“…1 About 50 million people in the world are affected by epilepsy and most of the population is from developing countries. 2 Although, epilepsy cannot be completely cured but its symptoms can be controlled with the treatment of antiepileptic drugs. 3 Carbamazepine (CBZ) is one of the anticonvulsant and antiepileptic drug used primarily for the treatment of epilepsy, neuropathic pain, and is a second line agent for the treatment of bipolar disorder and in some cases of schizophrenia.…”

Carbamazepine Loaded Vesicular Structures for Enhanced Brain Targeting via Intranasal Route: Optimization, in Vitro Evaluation, and in Vivo Study

“…CBZ has a specific mechanism to treat epilepsy by blocking sodium channel which leads to the delay of the recovery and decreases the firing's rate [3]. CBZ commonly exhibits the slow onset of action and systemic toxicity when administered via oral or intravenous (IV) routes due to the complex tight junctions between the endothelial cells of brain capillaries [4]. The intranasal route is the best choice to deliver CBZ directly to the brain, as this route exhibits several advantages as the good penetration and absorption of the small molecules, rapid delivery of therapeutic effect to blood and it can avoid metabolism by the first pass effect of the liver.…”

“…The intranasal route delivers the drug to the brain through different pathways as the olfactory pathway, trigeminal nerve pathway or vascular pathway. Different dosage forms as Nasal drops, sprays, gel, solution, and suspension can be used via the intranasal route [4].…”