The effect of particle size on the dehydration/rehydration behaviour of lactose

• Published in: International journal of pharmaceutics 2010-05, Vol.391 (1), p.38-47
• Main Authors: Crisp, J.L., Dann, S.E., Edgar, M., Blatchford, C.G.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; CP-MASNMR; Crystallization - methods; Desiccation - methods; Drug Stability; Ethanol - chemistry; General pharmacology; Humidity - adverse effects; Lactose; Lactose - chemistry; Medical sciences; Nanotechnology - methods; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymorph; Powders - chemistry; PXRD; SEM; Sub-micron
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2010.02.012

Ethanolic suspensions of spray dried and micronized alpha lactose monohydrate (Lα·H 2O) with average particle size between 3 and 200 μm, have been prepared and their dehydration behaviour was investigated by 13C CP-MASNMR spectroscopy. Sub-micron lactose suspension prepared by a novel high pressure homogenisation method has been compared with the standard ethanolic suspensions of Lα·H 2O prepared by reflux or static room temperature methods. In all cases, suspensions were shown to contain the stable anhydrous form of lactose (Lα S). Several approaches were employed to remove ethanol from these suspensions and the resulting dry lactose powders were then analysed by FT-IR, PXRD and SEM to evaluate the effect of drying procedure on type and distribution of lactose polymorphs and particle size. For samples with mean particle size greater than 1 μm, the stable anhydrous polymorphic form of lactose was retained on removal of the ethanol, although differences in the morphology and particle size of the crystals were apparent depending on method of suspension formation. Sub-micron Lα S, while stable in dry conditions, has been shown to be less stable to atmospheric water vapour than Lα S with particle size between 3 and 200 μm.