Carbamazepine Gel Formulation as a Sustained Release Epilepsy Medication for Pediatric Use

Abstract

This study aimed to develop a carbamazepine (CBZ) sustained release formulation suitable for pediatric use with a lower risk of precipitation. The CBZ was first prepared as sustained release microparticles, and then the microparticles were embedded in alginate beads, and finally, the beads were suspended in a gel vehicle. The microparticles were prepared by a solvent evaporation method utilizing ethyl cellulose as a sustained release polymer and were evaluated for particle size, encapsulation efficiency, and release profile. The beads were fabricated by the dropwise addition of sodium alginate in calcium chloride solution and characterized for size, shape, and release properties. The gel was prepared using iota carrageenan as the gelling agent and evaluated for appearance, syneresis, drug content uniformity, rheology, release profile, and stability. The microparticles exhibited a particle size of 135.01 ± 0.61 µm with a monodisperse distribution and an encapsulation efficiency of 83.89 ± 3.98%. The beads were monodispersed with an average size of 1.4 ± 0.05 mm and a sphericity factor of less than 0.05. The gel was prepared using a 1:1 ratio (gel vehicle to beads) and exhibited no syneresis, good homogeneity, and good shear-thinning properties. The release profile from the beads and from the gel was not significantly affected, maintaining similarity to the tablet form. The gel properties were maintained for one month real time stability, but the accelerated stability showed reduced viscosity and pH with time. In conclusion, CBZ in a gel sustained release dosage form combines the advantages of the suspension form in terms of dosing flexibility, and the advantages of the tablet form in regards to the sustained release profile. This dosage form should be further investigated in vivo in animal models before being considered in clinical trials.

Cellulose-Based Hydrogels as Sustained Drug-Delivery Systems

“…Microparticles from ethyl cellulose were prepared by a solvent evaporation method, in order to develop a sustained release formulation of carbamazepine (CBZ), suitable for dysphagic patients, especially for children below six years old [ 104 ]. The entire controlled drug-delivery (CBZ) system was accomplished by encapsulating the microparticles in alginate beads, which were then suspended in an iota-carrageenan gel ( Figure 9 ).…”

“… ( a ) Carbamazepine (CBZ)-alginate beads, ( b ) CBZ-gel prepared at a 1:1 ratio of beads to iota carrageenan gel [ 104 ]. …”

Carrageenan: Drug Delivery Systems and Other Biomedical Applications

“…Finally, the results of the physical stability studies showed that the gel formulation maintained its properties for a month when stored at 30 °C. The authors found that carbamazepine in a gel-sustained release dosage form combines the advantages of the suspension form in terms of dosing flexibility, and the advantages of the tablet form in regard to the sustained release profile [ 187 ].…”

Assessment of the biomarkers of hepatotoxicity following carbamazepine, levetiracetam, and carbamazepine-levetiracetam adjunctive treatment in male Wistar rats

“…The United States Food and Drug Administration (FDA) approved carbamazepine formulations include chewable tablets (Tegretol®), a suspension (Tegretol®), sustained release capsules (Carbatrol®), and sustained release tablets (Tegretol®-XR) since 1965 [ 9 ] It is widely accepted that carbamazepine (CBZ) [C 15 H 12 N 2 O] achieves its anticonvulsant properties by its interaction with different types of channels and receptors, while the main target of CBZ are voltage-dependent sodium channels [ 10 ]. Studies have shown that the pharmacologically active component of CBZ, carbamazepine-epoxide reduced the frequency of sustained repetitive firing of action potentials in cultured mammalian central neurons by inhibiting high frequency but not low frequency firing [ 10 , 11 ].…”