The pH profile of the lactose browning reaction was ascertained with various buffers under accelerated stability conditions and compared to the pH browning profile obtained by similar procedures for both dextrose and galactose. The effect of heat, humidity, and tablet lubricants was studied also. A correlation was found between the ultraviolet absorption spectrum and the 5-hydroxymethylfurfural content of samples of spray-dried lactose. The increase in absorption during the browning process afforded a simple procedure for studying this phenomenon. Also, absorption measurement could serve as a purity test for U.S.P. purposes. A procedure involving the use of anion exchange resins was developed for the purification of spray-dried lactose. This method should be adaptable to large scale commercial processes. Lactose which was spray-dried following this purification treatment was less susceptible to browning than the commercially available material.
AND COMPRESSIBILITY properties of FL:;ray-dried lactose (lactose S.D.) have led to an increased use of this material as an excipient in tablet and capsule formulations. However, the discoloration of such formulations is a problem and has been investigated by various workers. Gunsel and Lachman (I), evaluating the tableting properties of lactose, noted that while lactose S.D. was advantageous in several respects, it darkened more rapidly than conventionally processed lactose. The reason for this has not been clearly established. The significant differences between the two grades are that lactose S.D. contains (a) about 8% amorphous lactose, ( b ) slightly higher amounts of other sugars, metals, and ash and (c) that i t has been exposed to heat during the spraydrying process.
Webb (2) investigated the browning of lactose and other milk products and reported that the hydrogen ion concentration is of major importance and that phosphate buffer has a catalytic effect. However, the reaction was studied over a narrow pH range. Patton and Josephson (3) and Ramsey et al. (4) proposed that phosphates may be of secondary importance in the browning of milk products. A synergistic effect of phosphate and protein amino groups has been suggested by Pederson et al. (5). Recently, Brownley and Lachman (6) have demonstrated a relationship between the discoloration of lactose S.D. and the presence of free 5-hydroxymethylfurfural (HMF) .
The large-scale use of lactose in complex pharmaceutical formulations and the lack of ade-