Effect of Various Factors on the Corrosion and Rusting of Tooling Material Used for Tablet Manufacturing

Abstract

Various f a c t o r s t h a t cause t h e r u s t i n g o f t a b l e t punches anddies by a hydrochloride s a l t were evaluated. r i c h i n n i c k e l content was found t o have t h e b e s t r e s i s t a n c e t o r u s t i n g by t h e hydrochloride s a l t . humidity, temperature and c o n t a c t time w i t h t h i s hydrochloride s a l t were a l s o found t o be responsible f o r r u s t i n g o f t o o l i n g Tooling m a t e r i a l Other f a c t o r s such as materi a1 . The hydrogen c h l o r i d e l i b e r a t e d from t h e s a l t was found t o A c o r r e l a t i o n between the be t h e cause of r u s t i n g o f t o o l i n g . s t a b i i i t y o f hydrochloride s a l t as determined by thermogravim e t r i c a n a l y s i s and i t s e f f e c t on r u s t i n g o f t o o l i n g m a t e r i a l was demonstrated. Optimization o f t o o l i n g composition d u r i n g p r e f o r m u l a t i o n i s recommended.

Salt Disproportionation in the Solid State: Role of Solubility and Counterion Volatility

“…Volatilization of HCl, following disproportionation of HCl salt, has been reported in the literature. − Hydrochloride and methanesulfonate salts of triazole antifungal agent of the α-styrylcarbinol class (p K a = 1.7–2.2) were prepared, and stored at 60 °C. A loss of 12.7% of chloride ion was observed after 6 h of storage, in the case of its HCl salt.…”

“…The liberated hydrogen chloride gas either escapes from the system or reacts with other components of the formulation. , A proprietary hydrochloride salt, REV-6000-A­(SS), was found to liberate hydrogen chloride gas and thereby cause the rusting of tablet punches and dies. The thermogravimetric analysis of the salt indicated the loss of a mole of hydrogen chloride between 147 and 175 °C . Volatilization of HCl may also influence the chemical stability of an API.…”

“…The thermogravimetric analysis of the salt indicated the loss of a mole of hydrogen chloride between 147 and 175 °C. 29 Volatilization of HCl may also influence the chemical stability of an API. Lyophilization of quinapril HCl, in the absence of pH control, produced an amorphous mixture of salt and free base due to volatilization of a small amount of HCl.…”

The Utility of Sulfonate Salts in Drug Development

“…8 The driving force for this reaction is the generation of volatile hydrogen chloride gas that is either lost from the system or reacts with other components of the formulation/processing equipment leading to either de-stabilization and/or processing issues. 35,36 Narurkar et al 37 reported on the rusting of tablet tooling which was attributed to the liberation of hydrogen chloride gas from the hydrochloride salt of the API. A similar phenomenon also occurs during lyophilization where the high vacuum/low temperature combination tends to drive off labile hydrogen chloride gas from the corresponding hydrochloride salts.…”

Characterization of fentanyl HCl powder prior to and after systematic degradation

“…This is supported by the mass spectrometer data that found the fentanyl to remain between 99.00% and 99.76% pure throughout the degradation process. Additionally, the single mass‐loss event suggests hydrogen chloride is not lost prior to degradation of the fentanyl molecule as has been reported for other pharmaceuticals [16].…”