Formulation and evaluation of pediatric carbamazepine sustained release oral jelly

Abstract

Once daily epilepsy carbamazepine (CBZ) medication oral jelly for pediatrics was prepared and evaluated. The available marketed CBZ pediatric dosage form is CBZ suspension only which is not sustained release medication. Therefore, developing new CBZ sustained release oral jelly can play an important role to handle the following issues; (1) suitable dosage form for easy swallowing (2) reducing the multiple daily doses to one daily dose for patient convenience. This work consists of three parts, first one is to prepare CBZ sustained release microparticles, the second part is to incorporate the microparticles in alginate beads and the final one is to suspend the beads in oral jelly. The microparticles prepared by solvent evaporation method utilizing EC as sustained release polymer. Microparticles were evaluated for particle size, encapsulation efficiency (EE), in vitro release test, differential scanning calorimetry (DSC), attenuated total reflection–fourier transform infrared spectroscopy (ATR-FTIR), and high-pressure liquid chromatography (HPLC). CBZ release from microparticles was achieved and compared to the release of CBZ sustained release tablets of 200 mg stated in United States Pharmacopoeia (USP). The beads fabricated by crosslinking of sodium alginate with calcium chloride solution utilizing electrospray. CBZ beads were tested for the size, morphology, in vitro drug release and HPLC. In vitro release study results of CBZ from the beads showed the same release of CBZ in microparticles. Finally, the CBZ oral jelly prepared using an iota carrageenan gelling agent and evaluated for the dissolution test, syneresis, rheology, drug content uniformity, viscosity, physical appearance, and stability. CBZ loaded microparticle size ranged from 131 to 186 ?m. The highest EE was 96% for MP2 and the lowest one was 74% for MP9. The cumulative release percentage of CBZ at 24 h was ranged from 49% in MP1and 89% in MP10. CBZ bead results showed bead size of 1.4 mm for B2 and 3.5 mm for B4 with same EE of CBZ loaded microparticles. The release of CBZ from its beads was almost equal for all prepared bead formulations. In vitro drug release of CBZ was done firstly in the same conditions of dissolution test of CBZ beads and CBZ microparticles to ensure that there was no change in the release of CBZ when fabricated in iota carrageenan jelly. Secondly, comparison dissolution test study was carried out between CBZ oral jelly and Tegretol® XR 200 mg tablets and similarity factor was calculated to ensure that the CBZ jelly matching to the guidelines. Stable and homogenize CBZ oral jelly was obtained with the release similarity factor (F2) of 76 between CBZ oral jelly and Tegretol® XR 200 mg tablets under the same release conditions. The release of CBZ from the jelly found to be 94.11% from the original concentration after 24 hours. This study developed a new CBZ dosage form for pediatric patients with sustained release property and could be used as main and alternative treatment for pediatric epilepsy patients.