Compaction physics excipients

Coprocessed excipients have been mainly used in DC tableting because of their better flow ability and compressibility, and the excipient formed is a filler-binder. The compressibility of several coprocessed excipients such as Cellactose (45), SMCC (42,44), and Ludipress (BASF AG, Ludwigshafen, Germany) (46) have been reported to be superior to the physical mixtures of their constituent excipients. While comparing the compressibility profile of SMCC with MCC in the presence of high compression forces, the former was found to retain the compaction properties,... 

Dilution potential is the ability of the excipient to retain its functionality even after dilution with another material in a finite proportion. Most drug substances are poorly compressible, and require excipients to achieve better compressibility to retain good compaction even on dilution with them. Cellactose has been shown to possess a higher dilution potential than a physical mixture of its constituent excipients (50). 

The presence of amorphous lactose in the excipient may have a negative effect on compactibility and product stability. Direct compression grades of lactose monohydrate are available as granulated/agglomerated particles from multiple vendors. These physical properties are listed in Table 7.4. Commercial products combine the good flowability of coarse lactose crystals and the good compressibility... 

In essence, the test battery should include XRPD to characterize crystallinity of excipients, moisture analysis to confirm crystallinity and hydration state of excipients, bulk density to ensure reproducibility in the blending process, and particle size distribution to ensure consistent mixing and compaction of powder blends. Often three-point PSD limits are needed for excipients. Also, morphic forms of excipients should be clearly specified and controlled as changes may impact powder flow and compactibility of blends. XRPD, DSC, SEM, and FTIR spectroscopy techniques may often be applied to characterize and control polymorphic and hydrate composition critical to the function of the excipients. Additionally, moisture sorption studies, Raman mapping, surface area analysis, particle size analysis, and KF analysis may show whether excipients possess the desired polymorphic state and whether significant amounts of amorphous components are present. Together, these studies will ensure lotto-lot consistency in the physical properties that assure flow, compaction, minimal segregation, and compunction ability of excipients used in low-dose formulations. 

The physical properties of the solid state seen in crystals and powders of both drugs and pharmaceutical excipients are of interest because they can affect both the production of dosage forms and the performance of the finished product. Powders, as Pilpel reminded us, can float like a gas or flow like a liquid but when compressed can support a weight. Fine powders dispersed as suspensions in liquids are used in injections and aerosol formulations. Both liquid and dry powder aerosols are available and are discussed in Chapter 9 some properties of compacted solids are dealt with in Chapter 6. In this chapter we deal with the form and particle size of crystalline and amorphous drugs and the effect these characteristics have on drug behaviour, especially on drug dissolution and bioavailability. 

Similar behavior has been observed for noncrystallizing polymers. For example, the diffusivity of water in poly(vinylpyrrolidone) (PVP) (Oksanen and Zografi, 1993) has been shown to increase at water contents beyond the hydration limit. Additional reports have shovm that the hydration limit has physical significance for other polymer excipients. Microcrystalline cellulose and lactose for compression, for example, lose their direct compaction properties at water contents just below (Huettenrauch and Jacob, 1977), and gelatin capsules become brittle as the water content is reduced below Wm (Kontny and Mulski, 1989). Recently, the chemical stability of a model peptide in PVP matrices was shown to improve when the amorphous dispersion was stored below the polymer s hydration limit (Lai et al., 1999a Lai et al., 1999b Lechuga-Ballesteros et al., 2002). 

The physical properties of the drag substance and excipients are important in the manufacture, packaging, shipping, and use of drags [1]. These physical properties include solubility, dissolution rate, stability, particle size, water absorption, compactibility, and others. The crystalline form of the solid affects each of these properties. The physical form (i.e. polymorphism) of the drag substance can even affect the bioavailability of the drag and its effectiveness as a medicine [2]. Different solid-state forms of a chemical can be patented, thereby protecting the intellectual property of the pharmaceutical company, which can have a... 

---