Clopidogrel Bisulfate

Solid dispersions formulated to improve solubility & dissolution rate of poorly soluble drug Clopidogrel Bisulfate. Physical mixtures & solid dispersions of clopidogrel bisulfate were prepared with carboxymethylcellulose sodium and xanthan gum in the weight ratios of 1:1,1:3 and 1:5 using kneading method. The prepared solid dispersions were characterized by solubility determination, drug content, in vitro dissolution and accelerated stability studies. The results revealed that solid dispersions showned improvement in solubility and dissolution characteristics than the physical mixtures and pure drug. The reasons for increase in solubility and dissolution rate is decrease in particle size, increased surface area, amorphous state of the drug

In solubility study, excess of formulations (drug, PMs and SDs) were added to 10 ml of distilled water in a stoppered conical flasks and subjected to shaking for 8 h at 37±1oC and kept for 24 h after shaking to achieve equilibrium. 2 ml aliquots were withdrawn, filtered and after appropriate dilution with distilled water, filtrate was analysed at 220nm against blank. Readings were taken in triplicate and observations were recorded in table 1.

Drug content

Solid dispersions equivalent to 10mg of clopidogrel bisulfate were weighed accurately and dissolved in the 10ml of methanol. The solution was filtered, diluted suitably and drug content was analyzed at 220nm using UV spectrophotometer and observations were recorded (table 1).

Dissolution rate studies

The dissolution studies were carried out using dissolution apparatus (Rotating Paddle type) at a speed of 50 rpm. Accurately weighed amount of drug, PMs and SDs immersed in a pH 2.0 HCl buffer as dissolution medium at 37±0.5oC. The dissolution was carried out for 1 h and aliquot of 5ml was withdrawn at adequate intervals. The filtered samples were suitably diluted, assayed at 220nm and cumulative percentage of the drug dissolved from the formulations was calculated (table 2,

Dissolution Rate Studies

Solid dispersion of clopidogrel bisulfate showed a significant increase in the dissolution rate than the corresponding physical mixtures and pure drug. The dissolution rate increased on increasing the amount of polymers and maximum drug release was shown by FS3 (SDs with NaCMC 93.37±0.11%) and FS6 (SDs with Xanthan Gum 92.25±0.15%) as shown in table 2, 3.

Table 2: Cumulative % Drug Release of Solid Dispersion and Physical Mixture with Carboxymethylcellulose Sodium

Time (m) Drug FS1 FS2 FS3 FP1 FP2 FP3

0 0.00 0.00 0.00 0.00 0.00 0.00 0.00

10 2.67±0.11 6.98±0.29 8.65±0.21 10.35±0.12 4.67±0.18 5.19±0.27 5.95±0.21

20 5.89±0.25 17.83±0.69 22.50±0.15 25.87±0.54 10.85±0.23 12.36±0.29 15.58±0.34

30 12.46±0.10 29.56±0.21 38.07±0.82 43.20±0.09 19.15±0.93 24.22±0.16 27.94±0.26

40 20.08±0.17 41.83±0.92 50.19±0.27 57.15±0.36 31.09±0.24 36.80±0.41 40.98±0.17

50 27.92±0.47 65.95±0.17 74.42±0.12 77.82±0.22 48.81±0.35 51.69±0.23