Excipients glassy

Pharmaceutical solids can generally be described as crystalline or amorphous (or glassy). In fact, the actual solid phase composition of a pharmaceutical formulation is usually characterized by an intermediate composition, both crystalline and amorphous in character. In a multicomponent system, such as a solid formulation comprising drug and excipient(s), certain components or even a single component may be... 

Soluble matrix systems. The third matrix system is based on hydrophilic polymers that are soluble in water. For these types of matrix systems, water-soluble hydrophilic polymers are mixed with drugs and other excipients and compressed into tablets. On contact with aqueous solutions, water will penetrate toward the inside of the matrix, converting the hydrated polymer from a glassy state (or crystalline phase) to a rubbery state. The hydrated layer will swell and form a gel, and the drug in the gel layer will dissolve and diffuse out of the matrix. At the same time, the polymer matrix also will dissolve by slow disentanglement of the polymer chains. This occurs only for un-cross-linked hydrophilic polymer matrices. In these systems, as shown in Fig. 5.3, three fronts are formed during dissolution9-11 ... 

The mechanism of the protective effects imparted by the excipients has not been fully elucidated. Empirical observations have pointed to the following contributing factors formation of a glassy state of the protein-excipient system crystallinity of the excipients hydrogen bonding between the excipient and protein molecules and residual water content. 

The stability of glass-forming systems is also a matter of considerable importance. Early studies have explored the association between the glassy behavior and the chemical stability (80), whereas a number of investigations have examined the recrystallization behavior of glassy drugs and excipients. In essence, the increased molecular mobility above the glass transition temperature renders recrystallization... 

Claims have been made that the TBA does not enter into the product glassy phase.It has, however, also been reported that some TBA is indeed incorporated into the freeze-concentrate. If true, this might raise regulatory problems with pharmaceutical product registration. It is also not yet clear whether at temperatures in the region of Tg, the effect of TBA is unique. For instance, with sucrose-water systems, the presence of a volatile buffer salt (ammonium bicarbonate, acetate, formate) has a more marked effect on the sublimation rate than has TBA. On the other hand, with PVP-water systems, TBA is superior in enhancing the sublimation rate. It thus appears that the choice of excipient can also affect the drying rate. 

The variable properties of solids are coimected with the ability of molecules to exist in different states of order, ranging from closely packed molecular crystals with a minimum free energy to metastable crystal phases and, finally, to the glassy state with the highest free energy. This phenomenon is commonly referred to as polymorphism. Lattice defects in crystals and particularly solvate formation add another level of complexity. Whether a solid in any metastable state can be handled and analysed is a kinetic issue, which again is affected by many factors (e.g. chemical impurities, solvent residues, moisture, and interactions with drug excipients). 

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