Formulation of cilostazol spherical agglomerates by crystallo-co-agglomeration technique and optimization using design of experimentation

Abstract

Introduction:

Spherical agglomeration is one of the novel techniques for improvement of flow and dissolution properties of drugs. Cilostazol is a biopharmaceutics classification system Class II drug with poor solubility resulting in limited bioavailability. The present study aims at improving the solubility and dissolution of cilostazol by crystallo-co-agglomeration technique.

Materials and Methods:

Cilostazol agglomerates were prepared using various polymers with varying concentration of hydroxypropyl methylcellulose E 50 (HPMC E50), polyvinyl pyrrolidone K30 (PVP K30), and polyethylene glycol 6000. The influence of polymer concentration on spherical agglomerate formation was studied by 3 ² factorial design. Cilostazol agglomerates were evaluated for percent yield, mean particle size, drug content, aqueous solubility, and in vitro dissolution and further characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD).

Results:

The agglomeration process resulted in optimized formulation, F3 with mean agglomerate size of 210.0 ± 0.56 μm, excellent flow properties, approximately 15-fold increase in solubility than pure cilostazol and complete drug release in 60 min. Process yield, agglomerate size, and drug release were affected by amount of PVP K 30 and HPMC E50. The presence of drug microcrystal was confirmed by SEM, whereas FTIR study indicated no chemical change. Increase in drug solubility was attributed to change of crystalline drug to amorphous form that is evident in DSC and XRD.

Conclusion:

Crystallo-co-agglomeration can be adopted as an important approach for increasing the solubility and dissolution of poorly soluble drug.