The Measurement of the β/α Anomer Composition Within Amorphous Lactose Prepared by Spray and Freeze Drying Using a Simple (1)H-NMR Method.
Summary of "The Measurement of the β/α Anomer Composition Within Amorphous Lactose Prepared by Spray and Freeze Drying Using a Simple (1)H-NMR Method."
Reports of the anomeric composition of amorphous lactose are rare and state a highly variable range of composition (between 0% and 60% w/w β content). We aimed to develop a quantitative measurement by (1)H-NMR of α and β anomer content in amorphous lactose produced by different production methods.
Amorphous lactose was prepared by spray and freeze drying 10% w/v aqueous solutions of lactose. NMR analysis was performed in DMSO; peak areas of partially resolved doublets at 6.3 and 6.6 ppm were used to calculate % of α and β lactose present. Polarimetery was used to determine optical rotation of lactose solutions.
Observed specific rotation for supplied crystalline alpha lactose monohydrate of 88° recorded in DMSO was constant for the length of a typical NMR experiment (max. 10 min). β/α anomer contents of amorphous lactose measured by (1)H-NMR had standard deviations as low as 0.1% w/w (n = 6). Drying a lactose solution 4 h after its preparation led to almost 35% w/w difference in anomer composition within solid amorphous material compared to samples dried after only 30 min, e.g. for freeze dried samples, β content was 60 ± 0.1% w/w (4 h) and 25 ± 1.0% w/w (30 min). Mutarotation leads to this increase in β anomer concentration in aqueous solution and within the solid amorphous lactose stored at 25°C. e.g. after 56 d storage the β content of freeze dried lactose (30 min solution) increased from 25±1.0% to 50±0.5% w/w.
A simple solution-based (1)H-NMR method for measurement of anomeric composition of lactose has been established. The solution β/α ratio at the time of drying is mirrored in the composition of the resulting solid amorphous material. In order to produce a consistent anomer composition within spray and freeze dried amorphous lactose, the standing time for the feed solution should be greater than 4 h, such that the most dynamic region of the mutarotation profile has been exceeded. If the amorphous material has been formed from a solution that has not been allowed to equilibrate for 4 h, the resulting solid will continue to undergo mutarotation if trace amounts of moisture are present, until the anomeric β/α ratio slowly approaches 1.7.
Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
This article was published in the following journal.
Name: Pharmaceutical research
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21901569
- DOI: http://dx.doi.org/10.1007/s11095-011-0575-6
Medical and Biotech [MESH] Definitions
The condition resulting from the absence or deficiency of LACTASE in the MUCOSA cells of the GASTROINTESTINAL TRACT, and the inability to break down LACTOSE in milk for ABSORPTION. Bacterial fermentation of the unabsorbed lactose leads to symptoms that range from a mild indigestion (DYSPEPSIA) to severe DIARRHEA. Lactose intolerance may be an inborn error or acquired.
Plasmids which determine the ability of a bacterium to ferment lactose.
An enzyme of the transferase class that catalyzes the transfer of galactose from UDPgalactose to glucose, forming lactose. The enzyme is a complex of the enzyme N-ACETYLLACTOSAMINE SYNTHASE and alpha-lactalbumin; the latter protein is present in lactating mammary gland cells where it alters the usual specificity of the former to make lactose synthesis the preferred reaction. (Dorland, 28th ed) EC 220.127.116.11.
An amorphous form of carbon prepared from the incomplete combustion of animal or vegetable matter, e.g., wood. The activated form of charcoal is used in the treatment of poisoning. (Grant & Hackh's Chemical Dictionary, 5th ed)
An enzyme which catalyzes the hydrolysis of LACTOSE to D-GALACTOSE and D-GLUCOSE. Defects in the enzyme cause LACTOSE INTOLERANCE.
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