Evaluating the Bioavailability of Carbamazepine Using a Novel SNEDDS Formulation

Carbamazepine (CBZ) is an anticonvulsant drug primarily used to treat epilepsy, bipolar disorder, trigeminal and glossopharyngeal neuralgia. CBZ is a lipophilic, poorly soluble drug that belongs to the class-2 category according to the Biopharmaceutics Classification System. As a class-2 drug, the plasma concentration of CBZ is limited by its ability to diffuse across biological membranes. To increase its bioavailability, different methods such as crystal modifications, particle size reduction, amorphization, cyclodextrin complexation, pH modification, and self-emulsification were explored. Of these methods, Self Nano Emulsifying Drug Delivery Systems (SNEDDS) have shown to reduce particle size of CBZ molecules and improve its solubility. However, the bioavailability of CBZ administered as SNEDDS are not yet investigated. Given this background, the current study proposes to evaluate the bioavailability of these novel drug delivery systems using a rat model. The study is designed as a randomized controlled crossover experiment using 10-12 Sprague-Dawley rats divided equally into two groups. For this study, blood samples will be collected at 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes after administering two different formulations of CBZ nanoemulsions and stored at -20°C until ready for analysis. Plasma concentrations of CBZ will be determined by HPLC method. An unpaired t-test will be used to compare the significance between the two sets of data

Evaluating the Bioavailability of Carbamazepine Using a Novel SNEDDS Formulation

Central to the mechanism of how drugs work are the concepts of solubility and bioavailability. Drugs enter the body via absorption into the bloodstream, arrive at the target location, and bind to receptors to cause an effect. Drugs need to be soluble enough to pass through the cell membrane to enter and exit the bloodstream. Higher solubility generally correlates to higher bioavailability. Additionally, the smaller the particle size, the easier the drug will pass through the membrane into the blood plasma. Researchers have designed a system to categorize solubility class: Class I being high permeability and high solubility, Class II high permeability and low solubility, Class III low permeability and high solubility, and Class IV low permeability and low solubility. The study will use a Class II anticonvulsant, carbamazepine (CBZ). CBZ is a suitable candidate for this study because it requires a higher bioavailability due to its need to cross the blood brain barrier and act on the trigeminal nucleus. To increase bioavailability researchers have tried crystal modifications, particle size reduction, amorphization, cyclodextrin complexation, pH modification, and self-emulsification. These methods have been successful at increasing bioavailability, but this experiment will focus on reducing particle size into a new self-emulsifying formulation. In particular, the formulation of CBZ in this study is a self nano-emulsifying drug delivery system (SNEDDS), which shows more promise than previous methods to increase bioavailability. This study will create a SNEDDS formulation as a nasal nebulizer mist delivery and compare it to a FDA approved oral suspension using a crossover rat model design. Sixteen Sprague-Dawley rats will be ordered through Central State University and normalized to the study environment for a minimum of one week. Pending IACUC approval from Central State University, the tail vein method will be used to collect blood samples. The samples will be stored until needed for analysis using ELISA, enzyme-linked immunosorbent assay, which will be used to determine the concentration of CBZ in blood plasma