Prediction of quality attributes (mechanical strength, disintegration behavior and drug release) of tablets on the basis of characteristics of granules prepared by high shear wet granulation

Abstract

High shear wet granulation is commonly applied technique for commercial manufacturing of tablets. Granulation process for tablets manufacturing is generally optimized by hit and trial which involves preparation of granules under different processing parameters, compression of granules and evaluation of the resultant tablets; and adjustment is made in granulation process on the basis of characteristics of tablets. Objective of the study was to optimize the process of high shear wet granulation and prediction of characteristics of tablets on the basis of properties of granules. Atenolol granules were prepared by high shear wet granulation method, using aqueous solution of polyvinyl pyrrolidone (PVP k-30) as binder. Concentration of binder solution and granulation time were taken as process variables, both studied at three levels. Different combinations of process variables were determined by Design Expert software. Granules were evaluated for different parameters on the basis of SeDeM-ODT (Sediment Delivery Model-Oro Dispersible Tablets) expert system. Granules from all the trials were compressed using round (10.5 mm) flat faced punches at compression weight of 250 mg/tablet. Tablets were evaluated of different quality control parameters as per USP. Results showed that both the process variables had positive effect on mechanical strength of tablets and negative effect on disintegration and dissolution rate. Granule prepared with highest level of binder concentration (15%) and highest granulation time (60 sec) resulted in tablets with highest crushing strength (11.8 kg), specific crushing strength (0.328 kg/mm2), tensile strength (0.208 kg/mm2), lowest value of friability (0.19%) and highest disintegration time (10.9 min), as predicted from granules characteristics on the basis of SeDeM-ODT expert system. Drug release from Trial-13 (processed under highest level of both process parameters) was also lower than rest of the trials. It is concluded from the study that quality characteristics of tablets can be predicted from granules characteristics using SeDeM-ODT expert system. Furthermore, SeDeM-ODT expert system can also be used for optimization of the process of high shear wet granulation.

Effects of carboxymethylated gum obtained from Entandophragma angolense tree on the compressional and release properties of ibuprofen tablets

“…A formulation scientist needs to understand the forces that contribute to bond formation and breakage within a tablet matrix [16]. Attractive forces occurring between the components of the formulations (such as binders, APIs and other excipients) are all critical factors that affect not only the mechanical properties of the tablets but also the rate and extent to which the API is released from the tablet matrix [17]. The parameters obtained from the Heckel and Kawakita plots are presented in Table 2, while Figure 2 and 3 show representative Heckel plots for polymers incorporated at 5.0% w/w and Kawakita plots for the carboxymethylated Entandophragma angolense gum (CENTA) respectively.…”

“…The parameters obtained from the Heckel and Kawakita plots are presented in Table 2, while Figure 2 and 3 show representative Heckel plots for polymers incorporated at 5.0% w/w and Kawakita plots for the carboxymethylated Entandophragma angolense gum (CENTA) respectively. The compaction of powders involves a volume reduction process on the application of an external pressure [17]. Generally, the ranking of the Py, calculated from the regions of the Heckel plots showing the highest correlation coefficient for the plots is ENTA > CENTA > gelatin BP.…”

Effect of Mannitol Particle Size on Melatonin Dissolution and Tablet Properties using a Quality by Design Framework

“…Disintegration time of the ODT formulations was less than 30 seconds, but formulations containing M100 had a faster disintegration time compared with formulations containing larger mannitol particles (M200), as seen in Figure 1 (39). Tablets were prepared using wet granulation followed by tableting, which could produce granules with a smaller size distribution, which can positively impact the mechanical strength of tablets and negatively impact disintegration time and dissolution rate (40).…”

Modification of Bulk Density, Flow Property and Crystallinity of Microcrystalline Cellulose Prepared from Waste Cotton

“…Moreover, a powder mixture with low bulk density requires an excess force to apply for tablet formation while increased bulk density powder may be exposed to insufficient pressure, both may result in crushing or capping problems for tablets [ 25 ]. In contrast, the flow property is directly associated with the ease of transfer of powder mixture from the hopper to the die cavity in appropriate amounts and variation of this property affects the dose uniformity of tablet [ 26 ]. Additionally, crushing strength which depends upon the compressibility of the powder affects the disintegration and subsequent dissolution of the drug in the gastrointestinal tract.…”

“…Additionally, crushing strength which depends upon the compressibility of the powder affects the disintegration and subsequent dissolution of the drug in the gastrointestinal tract. Hence, proper crushing strength is essential for quality products [ 25 , 26 ].…”