The crystallization and caking of amorphous lactose in mixtures with α-lactose monohydrate powder

Commercial bulk lactose powders commonly contain amorphous lactose. It may be produced intentionally to improve product solubility and tablet compaction (e.g. spray-drying) or unintentionally (e.g. milling). The content of amorphous lactose in bulk powders is difficult to adjust. Materials with a relatively small amorphous content might exhibit significant changes in behaviour which can have serious consequences for drug stability and materials handling. Partially caked lactose powders can be difficult to convey and cause blockages and breakdowns in feeders and tabletting machines. The presence of more than 10% amorphous lactose causes caking in lactose powder under pressure (1.4 MPa, corresponding to a load of 25 kg over a standardized contact area 1.77x10-4 m2). The texture analyzer was used to prepare and analyze plugs of lactose. Storage at 33% relative humidity (25⁰C, 3 months) did not markedly change the hardness of the caked lactose plugs. Storage at 57% and 75% relative humidities (25⁰C, 3 months) markedly increased the hardness of the caked lactose plugs when the lactose powder initially contained 50% amorphous lactose and above. The lactose plugs reduced in size after storage. Exposure of amorphous lactose to humid air (75% relative humidity, 25⁰C, 3 months) did not result in complete crystallization when the amorphous lactose was less than 10% in the bulk powder. However, when there was 25% amorphous lactose or more in the bulk powder, all of the amorphous lactose crystallized after exposure to a relative humidity as low as 33%. These results will be used to develop an understanding of how to avoid the formation of amorphous lactose and hence how to control caking in bulk lactose powders.