Formulation and Process Optimization of Cinnarizine Fast-Release Tablets - Pharmaceutical Technology

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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.


Pharmaceutical Technology
Volume 33, Issue 8, pp. 53-59

Results and discussion


Table I: Experimental conditions used to study the effect of binder and process parameters.
DSC analysis. DSC curves obtained for powdered CNZ, lactose monohydrate, PEG 6000, and granules prepared by melt granulation are shown in Figure 2. Pure powdered CNZ exhibited a melting endotherm at 125.54 C. DSC scans of lactose monohydrate and PEG 6000 showed single sharp endotherms at 154.65 and 69.08 C, respectively, due to melting of both compounds.


Figure 3: Size distribution of granules prepared with various binder concentrations. (FIGURE IS COURTESY OF THE AUTHORS)
DSC thermograms of granules of CNZ, lactose monohydrate, and PEG 6000 showed an absence of CNZ and the presence of sharp endothermic peaks because of the melting of PEG 6000 and lactose monohydrate. This complete absence of CNZ peak indicates that CNZ is present as amorphous or as a solid solution inside the PEG matrix.


Figure 4: In vitro dissolution of granules prepared with various binder concentrations. (FIGURE IS COURTESY OF THE AUTHORS)
Effect of binder concentration. The various granulation batches prepared to study the effect of binder concentration are listed in Table I (batches M1–M3). Figure 3 shows the particle-size distributions of the granules prepared using various binder concentrations. Ungranulated fines decreased as the concentration of PEG increased from 10.0% to 20.0% (w/w). Particle-size distribution widened as the PEG content of the feed increased from 10.0% to 20.0% (w/w). When granulation was attempted with a PEG content of 25% (w/w), slurry was produced (i.e., the system was over-wetted and defluidized). In Figure 3, there is evidence of the emergence of overwetting in the granulation with a feed with PEG content of 20 % (w/w).


Figure 5: Size distribution of granules prepared with binder of various particle sizes. (FIGURE IS COURTESY OF THE AUTHORS)
The in vitro dissolution rate of all prepared granulates increased compared with that of the drug alone. This increase is a result of the higher hydrophilic character of the systems due to the carriers and the slight reduction of CNZ crystallinity (see Figure 4). No significant in vitro dissolution differences were attested among the granules prepared using various concentrations of the binder.


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