Stability Data Packaging Concerns

Inhalation drug products include inhalation aerosols (metered dose inhalers) inhalation solutions, suspensions, and sprays (administered via nebulizers) inhalation powders (dry powder inhalers) and nasal sprays. The CMC and preclinical considerations for inhalation drug products are unique in that these drug products are intended for respiratory tract-compromised patients. This is reflected in the level of concern given to the nature of the packaging components that may come in contact with the dosage form or the patient. 

---

When the PVC unzippers, it discolors and becomes brittle. To prevent this dehydrochlorination reaction, heat stabilizers are added. Lead stabilizers are effective and a major type of heat stabilizer. Data from 2003 [24] shows lead stabilizers to represent more than 50% of the world PVC stabilizers, but less than 20% in the U.S. where tin stabilizers predominate. The use of lead stabilizers is on the decline and being phased out due to concerns about the health effects of lead. Nonetheless, the news occasionally reports that lead has been found in a toy or other PVC article imported from a country such as China. The source of lead is likely due to the stabilizer. Another type of heat stabilizers is the mixed metal packages which are based upon mixtures of different... 

Cyclodextrins have had valuable industrial uses for a considerable time, particularly as agents to bind or release volatile molecules. Accurate predictions concerning the selectivity and stability of cyclodextrin-guest complexes are therefore of considerable interest both academically and practically." MD was used to simulate cyclodextrin hydrates" as a test of the applicability of the GROMOS program package to systems beyond proteins and nucleic acids. Other early MD simulations focused on interactions with guests such as enantiomers of methyl-2-chloropropionate. Comparisons between calculated thermodynamic properties for complexes formed by O -cyclodextrin with para-substituted phenols and the results of MM simulations led to improvements in force fields that described the interactions. MM2 simulations were used to support NMR data for the -cyclodextrin inclusion complex with benzoic acid. " The well-known catalytic effect of cyclodextrins has been modeled. For example, the relative rate increase of hydrolysis of S over R phenyl ester stereoisomers in the presence of -cyclodextrin... 

---