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 9: Granule size distribution after various granulation times. (FIGURE IS COURTESY OF THE AUTHORS)
An SEM study (see Figure 8) showed that at 10 min of granulation, the mechanism of granule growth was nucleation, and at 20
min, nucleation was followed by agglomeration, whereby initial nuclei were formed and coalescence of particles took place.
Figure 10: Granule size distribution at various fluidized air velocities. (FIGURE IS COURTESY OF THE AUTHORS)
Effect of fluidizing air velocity. The data presented in Table I show the operating conditions used to investigate the influence of fluidizing air velocity
(batches M11–M14). The variation in median size correlated with increased fluidizing air velocity. In all cases, the granule
size was lower at a higher velocity. At the lowest fluidizing air velocity (350 m3/h), reduction in solids motion resulted in local overwetting, thus causing the defluidization of the bed. As the fluidized
air velocity increased from 450 m3/h to 650 m3/h, mean granule size decreased, which may be attributed to the increase in the number of collisions at a faster velocity
(see Figure 10).
Figure 11: Scanning electron microscopy (SEM) images of granules produced at (a) 60 °C and (b) 68 °C. (FIGURE IS COURTESY
OF THE AUTHORS)
Effect of bed temperature. Table I lists the experimental conditions used to study the effect of bed temperature (batch M15–M18). At 60 °C, materials
are completely fluidized and granules were produce with superior characteristics. When granulation was attempted at higher
temperatures (64 and 68 °C), the bed defluidized and many lumps formed. The main cause for this occurrence is that these operating
bed temperatures fall within the melting range of the binders, thereby inhibiting binder solidification to form granules.
The authors' investigation into the influence of bed temperature using PEG 6000 clearly showed that the mean diameter of granules
increased with increased bed temperature. The former observation can be explained by the hypothesis of Vander Scheur on the
basis of the difference in binder solidification and heat transfer rate at increased bed temperature. For example, a higher
bed temperature will induce a slower binder solidification rate, and the binder will remain molten for a longer period. This
means the binder will have more time to promote more particle aggregation before it solidifies, thus leading to a faster growth
rate with increased bed temperature (15).
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
What do you think the role of continuous (rather than batch) processes in pharmaceutical manufacturing will be over the next five years?
Many companies in the industry will be using continuous processes for some products.
Companies in both pharmaceutical and biopharmaceutical production will be evaluating continuous processes but few will implement.
Only a few companies will be evaluating or implementing; most will stay with batch processing.