Compaction of lactose drug mixtures: Quantification of the extent of incompatibility by FT-Raman spectroscopy

Abstract

It is well known that lactoses interact with drugs containing amino groups and undergo the Maillard reaction. Lactose monohydrate may also interact with moisture sensitive drugs and affect the stability of the drug. These interactions were analyzed using three model drugs – Thiaminchloride hydrochloride, Nicotinamide and Acetylsalicylic acid – which interact with spray-dried lactose or anhydrous lactose. FT-Raman spectroscopy was used for the first time to qualitatively and quantitatively analyze these excipient drug interactions in powders and tablets. Both lactoses undergo the Maillard reaction with Thiaminchloride hydrochloride. Nicotinamide did not react with the lactoses because the amide group is protected against the reaction with the lactoses. Only a transition from β- to α-lactose was noticed. The moisture sensitive drug Acetylsalicylic acid remained stable even when the tablets were stored under accelerated conditions (40 °C and 75% RH). The crystal water of lactose monohydrate (spray-dried lactose) had no influence on the drug stability but a transition from β- to α-lactose was noticed. In conclusion, FT-Raman spectroscopy is a fast and valuable tool for a quantitative determination of the extents of incompatibility in solid dosage forms.