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34 May 2015 Tablets & Capsules Table 1 Specifications and methodology of study Placebo methods: • 20-mesh screen; varying levels of lubricant; blend with MCC or SMCC; mix using Turbula blender for varying amounts of time. • Amounts of lubricant used: 0.5, 1.0, and 2.0% MgSt. • Blending times: 5 minutes, 20 minutes.* • Materials compressed with instrumented rotary tablet press that recorded compaction and ejection forces. • Tablets analyzed for hardness/crushing strength. API model methods: • 20-mesh screen; lubricant; blend with MCC or SMCC and 20 percent CPM; mix using Turbula blender for varying amounts of time. • Amounts of lubricant used: 0.5% MgSt or 0.5% SSF. • Blending times: 5 minutes, 20 minutes.* • Materials compressed with instrumented rotary tablet press that recorded compaction and ejection forces. • Tablets analyzed for hardness/crushing strength. * Note: In this study, blend times denote the period that the formulation spent undergoing blending in a high-energy lab-scale Turbula-style blender. In a production setting, true blend times and the shear applied are often difficult to measure. Furthermore, blending actually continues as the formulation is transported, transferred, and fed through the hopper onto the turret. It only really ends when the tablet is compressed. While blending time is usually held constant over the lifespan of a formulation, equipment and manufacturing sites may change, causing the shear force and true blend time to vary, which could lead to failures. The same trends are evident from the tests of the MCC formulation, ex - cept tablet hardness is much lower (data not shown). Similar trends are evident in a placebo formulation that used SSF as the lubricant, but there wasn't as much reduction in tablet hardness (data not shown). Baseline functionality of an excip- ient matrix in placebo formulations is useful, but the addition of APIs and how much is added dictate ulti- mate func tionality. Likewise, studies with mo del APIs can help you iden- tify is sues to anticipate when manu- facturing with comparable APIs. Figure 2 shows that SMCC formu- lated with a model API (CPM) and lubricated with MgSt has a substan- tially better compaction profile than a formulation that in cludes premium spray-dried MCC, regardless of the blend times. Note that tablet hard- ness increases consistently with compaction force in the SMCC for- mulation, while doubling the com- paction force applied to the MCC formulation improves hardness on ly negligibly and somewhat un even ly. It is noteworthy that the SMCC pro- files have steeper slopes, suggesting har der tablets are achievable. The same methods and equipment were used to compress formulations that included SSF instead of MgSt (Figure 3). Once again, the SMCC formulations had substantially better compaction profiles than the MCC ver sions. (All formulations had ac - cept able ejection forces.) As Figure 4 shows, combining SMCC and SSF produced very robust formulations, with a fivefold or greater increase in tablet hardness. This suggests that these excipients offer a broad design space without compromising CQAs. While the characteristics of a for mu - lation depend upon the specific API(s) used, this study using a model API re - flects the same trends seen in the pla ce - bo studies. Understanding these trends may help you substantially re duce development time, require less ma terial, and simplify risk-mitigation studies. In sum, the evidence examined in this study supports the assertion that the cost of failures and delays associ- ated with scale-up and production using common excipients outweighs the higher costs of HFEs. T&C F P P TABLETS & CAPSULES o r m u l a t i o n r o d u c t i o n a c k a g i n g J un e 20 15 Tablets & Capsules SOLID DOSAGE SOURCEBOOK June 2014 Solid Dosage Sourcebook Coming in June The T&C Solid Dosage Sourcebook — Spotlighting the top companies that supply equipment, materials, and expertise to manufacturers of pharmaceuticals and dietary supplements.