Chemical Stability of Amorphous Materials: Specific and General Media Effects in the Role of Water in the Degradation of Freeze-Dried Zoniporide

The Importance of Individual Protein Molecule Dynamics in Developing and Assessing Solid State Protein Preparations

“…Of course, the final water amount, or amount of any plasticizer/good hydrogen‐bonding additive that is present in the bulk amorphous material, needs to be low enough so as not to overplasticize the system and render it a poor bulk amorphous material at the storage temperature . Besides the poorer physical stability, excess water is also an excellent enabler of protein chemical degradation mechanisms . Although, theoretically speaking, managing the water content certainly appears to be the best practice, operationally speaking, this can be difficult to accomplish, as for many freeze‐drying procedures, there is a delicate balance between managing the benefits of obtaining that optimal water content and the risk of “overdrying.” However, as we are emphasizing, it is the resulting final solid‐state mixture composition that appears to determine the successful long‐term storage stability, so the investments in properly controlling the drying risks are critical to developing the proper solid‐state material.…”

Excipient Selection in Oral Solid Dosage Formulations Containing Moisture Sensitive Drugs

“…Although excipients are considered to be inert in therapeutic or biological actions, they should also not cause any unwanted changes to the drug such as phase transitions or degradation and thus ensure the required stability of the API in the formulation during manufacturing and shelf life. The type and quantity of the excipients used in drug formulations can have a significant effect on final product stability (Cunningham et al 2001;Moribe et al 2007;Flemming and Picker-Freyer 2008;Islam et al 2008;Konno and Taylor 2008;Luthra et al 2012). Materials that are included in solid dosage forms contain inherent moisture, which may act both as a reagent and/or reaction medium (Waterman et al 2002).…”

“…Hydrolytic reactions are amongst the most common processes for drug degradation (Waterman et al 2002;Airaksinen et al 2003Airaksinen et al , 2005aJørgensen et al 2004;Waterman and Adami 2005;Heidarian et al 2006;Luthra et al 2012).…”

Water Clusters in Amorphous Pharmaceuticals

“…One such case was reported in Ref. 76 in which the impact of water on amide hydrolysis of a model drug, zoniporide, in the amorphous solid state was investigated and difference in the shape of the degradation curves between dry samples and samples with elevated water contents was noted. For a nominally dry sample (water content 0.1-0.3 wt %), the hydrolysis kinetics followed zero-order process, whereas the kinetic curves for samples exposed to RH 6% and 11% RH were best described using C = f(t n ) dependence, where C is concentration of the degradant, t is time, and the exponent n was determined to be between 0.5 and 1.…”