Formulation and Process Optimization of Cinnarizine Fast-Release Tablets
The authors prepared granules containing cinnarizine using polyethylene glycol 6000 as a melting binder and lactose monohydrate as hydrophilic filler. The effects of binder concentration and size were studied.
Figure 6: Scanning electron micrograph of granules prepared with poly(ethylene glycol) 6000 of particles size (a) 642 μm,
(b) 343 μm, and 195 μm. (FIGURE IS COURTESY OF THE AUTHORS)
Effect of binder particle size. Various granulation batches prepared to study the effect of binder particle size on granule characteristics are listed in
Table I (batches M4–M6). The size distribution of granules prepared with binders having various particle sizes is shown in
Figure 5. These data indicate that particle-size distribution widened as the particle size of PEG increased from 195 to 642
μm. Granule size was directly proportional to the binder particle size (see Figure 6). Particles are easily agglomerated with
the binder's larger particle size.
Figure 7: In vitro dissolution of granules prepared with binder of various particle sizes. (FIGURE IS COURTESY OF THE AUTHORS)
In vitro dissolution profiles of granules prepared using a binder of various particle sizes are shown in Figure 7. The in vitro dissolution rate of all prepared granulates improved compared with that of the drug alone because of the superior hydrophilic
character of the systems. A slight increase in dissolution rate was observed with a decrease in the binder's average particle
size from 642 to 195 μm.
Figure 8: Scanning electron microscopy (SEM) image of granules at (a) 10 min granulation time, 21 × magnification, (b) 10
min granulation time, 127 × magnification, (c) 20 min granulation time, 21 × magnification, (d) 20 min granulation time, 127
× magnification. (FIGURE IS COURTESY OF THE AUTHORS)
Effect of granulation time. Table I lists the experimental conditions used to study the effect of granulation time (batches M7–M10), and Figure 9 shows
a plot of cumulative mass fraction versus particle size with respect to granulation time (PEG 6000). The data indicate a considerable
increase in particle size from the initial distribution to a granulation time of 5 min, with further granule growth occuring
between 5 and 10 min. After 10 min, the particle-size distribution increased slightly (PEG content 15% w/w). It is interesting
to note that the percentage of granules between 0.44 and 1.6 mm, the typical particle size range for pharmaceutical tablet
pressing, was in excess of 50% for a granulation time of 10–20 min. These results are indicative of nucleation followed by
the agglomeration process, whereby initial nuclei are formed and coalescence of particles takes place. However, further granule
growth is limited to a relatively short time period. Because of the relative particle size of the binder and powder, the nucleation
process is probably immersion nucleation, whereby the lactose powder adheres to and immerses into the molten PEG particles
(14). Some previous studies on melt granulation indicate that nucleation and coalescence are the predominant growth regimes
Rakesh P. Patel is an associate professor in the Department of Pharmaceutics and Pharmaceutical Technology, S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Gujarat, India.
Articles by Rakesh P. Patel
Ajay Suthar is a postgraduate at the department of pharmaceutics of S.K. Patel College of Pharmaceutical Education and Research, Ganpat Vidyanagr, Kherva, India 382711.
Articles by Ajay Suthar
How does your company apply quality-by-design (QbD) principles to manufacturing processes?
To all processes for both new and legacy products
To all process for new products only
To select process for new products only
To select processes for both new and legacy products