Amiodarone is antihypertensive drug with variable bioavailability following oral administration due to poor solubility and pre-systemic metabolism. Accordingly, the study strategy was to enhance the dissolution rate of the drug by solid dispersion (SD) and surface solid dispersion (SSD) techniques, with optimum formulations being developed as fast disintegrating tablets with rapid release. Binary and ternary SD were prepared using Pluronic F68, Pluronic F127 and PVP k30 as the hydrophilic polymers. SSD were prepared employing Pluronics and Aerosil as polymer and carrier, respectively. Both SDs and SSDs increased the dissolution rate compared to pure drug and physical mixtures. Thermal analysis revealed reduced drug crystalinity Ternary SD and SSD were selected to prepare a series of fast disintegrating tablets. Unprocessed drug in the fast disintegrating matrix was used as control. Tablets were prepared by direct compression technique using croscarmelose as superdisintegrant. Effect of using Avicel PH102 or mannitol as filler was also investigated. All tablets showed better dissolution parameters compared to control. Tablets prepared using SSD and employed mannitol showed the highest drug release after 5-min. The study thus developed fast disintegrating tablets with rapid drug dissolution with the potential of increased oral bioavailability by reducing pre-systemic metabolism due to Pluronic polymers.
Key words: Amiodarone, enhancing dissolution, solid dispersion, surface solid dispersion, fast disintegrating tablets
|
