The present study proposes to enhance solubility and eventually bioavailability of
Atorvastatin Calcium (ATV) by preparing hot melt extrusion based orodispersible tablet (ODT). Tablet
dosage forms displaying faster disintegration providing significant advantages over traditional
techniques of solid dispersion (SD) were made by a speedy method. Dissolution analysis of the
extrusion processed ATV using Soluplus in combination with Kolliphor TPGS (1:2:0.5) showed
significantly increased dissolution rates and extent of supersaturation over pure drug. DSC and XRD
studies revealed that ATV is converted to amorphous form during extrusion. A design of experiments (DOE) was
conducted on ODT formulation to evaluate the effect of compression force and Kollidon CL-SF (super disintegrant)
concentration on disintegration time, friability and hardness (p value <0.0001). The optimum formulation showed
disintegration time 33±1.52 Sec, friability 0.91±0.035%, hardness 3.8±0.15 kg/cm2 and 91.18±1.2 % drug release within
15 min, thus comply US-FDA standard. The in vivo study revealed that the rate and extent of absorption of prepared tablet
were higher than pure drug and marketed tablet. Cmax value of optimized formulation was 67.42±1.45 μg/ml, obviously
higher than that of pure drug and marketed formulation which was 19.04±1.26 µg/ml and 56.11±1.64 µg/ml respectively.
Similarly, Tmax value of former, 120 min significantly earlier compared with that of drug and marketed formulation which
was 360 min and 240 min. Furthermore, Short-term accelerated stability study showed that tablets were stable at 40 °C
and 75% RH as per ICH guideline.
Keywords: Atorvastatin calcium, central composite design, hot melt extrusion, orodispersible tablet.
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