Formulation Evaluation and Optimization of Mebendazole Colon Targeted Sustain Release Pellets by Extrusion Spheronization

Abstract

The aim of present investigation is to formulate evaluate and optimization of colon targeted pellets bearing mebendazole, benzimidazole derivative with broad spectrum of anthelminthic activity. It is highly effective against adult and larval stages of ascaris lumbricoids, hook worms and  indicated for the treatment of nematode infestation. Pellets were prepared by extrusion spheronization process using microcrystalline cellulose as spheronizing aid, natural polysaccharide pectin as binders in three different percentages i.e 5%, 10% and 15% and glycerine as plasticizer.  Further study was carried out to select the natural polysaccharide for formulation of colon targeted pellets i.e. Pectine, Xanthan gum and Guar gum. The formulation were prepared with optimized constant process parameters i.e. Percentage LOD 10%, Spheronization time 3 minutes and Speed of spheronization 700-1200 rpm. Prepared A1 – A9 batches were then evaluated by their micromeritic properties like tapped density, carr’s index, hausner, S ratio, angle of repose  and characterized by microscopic study, % yield, hardness, friability, % assay and dissolution study was carried out and compared with marketed formulation by statistical analysis similarity factor (f₂). The batch A5 is having 10% pectin, 18% MCC and 20% mebendazole shows (22.20±2.05) % carr’s index, (1.22±0.04) hausner’s ratio, (26.65±1.15) angle of repose, (88.2±2.36) % yield, (3.96±0.46) hardness, (0.23±0.03) % friability  (88.47±3.26) % assay and (99.81±3.80) % drug release after 10 hours. Pellets equivalent to 300mg of mebendazole  were then filled in capsules and capsules coated with 12.5% w/v Eudragit S 100 using optimized 4- 5 ml/min spray rate, 15 rpm pan speed and 40±5°C coating inlet temperature and then optimized for % weight gain in four different trials. W2 batch having 10% weight gain were then evaluated by % cumulative drug release, disintegration test in 0.1 N HCl shows (99.73±3.34) % CDR, intact after 12 hours. The pellets of batch A5 and the enteric coated capsule with 10 % weight gain were packed in aluminum pouch and charged for accelerated stability studies at (40°C±2°C) and (75%±5%) RH for 1 month in a stability chamber shows no change in the dissolution profile at (40°C±2°C) and (75%±5%) RH storage condition.