Effects of poloxamer and HPMC on the dissolution of clonazepam-polyethylene glycol solid dispersions and tablets

Clonazepam is an anticonvulsant and anxiolytic drug characterized by poor solubility and rapid absorption. The purpose of the study was to improve the solubility of clonazepam in solid dispersions by incorporating hydroxypropyl methyl cellulose (HPMC) and poloxamer 407. Solid dispersions were prepared by using polyethylene glycol 6000 as carrier in 1:20 ratio by melt granulation. The solid dispersions were compressed in to tablets by adding microcrystalline cellulose, sodium starch glycolate and talc. The solid dispersions were characterized by differential scanning calorimetry, particle size analysis, and drug contents were measured by HPLC coupled with UV detection. The in vitro dissolution of the tablets was compared with pure drug in 900 ml water using USP dissolution apparatus (type II). HPMC improved the solubility of clonazepam by decreasing its particle size and drug dissolution from the tablets also increased significantly (p<0.05). The thermograms of poloxamer containing formulations indicated that clonazepam could be in molecularly dispersed form. Unlike HPMC, significant increase in drug solubility and dissolution (p<0.05) was observed with smaller amount of poloxamer. From the results it was concluded that both crystallization inhibitor (HPMC) and wetting agent (poloxamer) in solid dispersions can improve solubility and release profile of poorly soluble clonazepam.