The Measurement of the β/α Anomer Composition Within Amorphous Lactose Prepared by Spray and Freeze Drying Using a Simple 1H-NMR Method
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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 1H-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 1H-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 1H-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.
KEY WORDSamorphous freeze drying lactose NMR spray drying β/α anomer composition
ACKNOWLEDGMENTS & DISCLOSURES
This work was supported by a Dorothy Hodgkin Postgraduate Award DHPA funded by the EPSRC and Cadbury Plc / Kraftfoods Inc.
- 4.Wade A, Weller P. Handbook of pharmaceutical excipients. 2nd ed. Washington, DC: American Pharmaceutical Association; 1994.Google Scholar
- 6.Street CA. Flour confectionery manufacture. New York: Blackie Inc VCH publishers; 1991.Google Scholar
- 7.McSweeney PLH, Fox PF. Advanced dairy chemistry: volume 3: lactose, water, salts and minor constituents. New York: Springer Science; 2009.Google Scholar
- 8.Fox PF, McSweeney PLH. Dairy chemistry and biochemistry. New York: Kluwer Academic/Plenum publishers; 1998.Google Scholar
- 9.Aulton ME. Aulton’s pharmaceutics: the design and manufacture of medicines. 3rd ed. Edinburgh: Churchill Livingstone Elsevier; 2007.Google Scholar
- 12.McMurry J. Organic chemistry. 6th ed. Belmont: Brooks/Cole; 2004.Google Scholar
- 18.Roetman K, Schaik MV. The β/α ratio of lactose in the amorphous state. Neth Milk Dairy J. 1975;29:225–37.Google Scholar
- 24.Buckton G, Chidavaenzi OC, Koosha F. The effect of spray-drying feed temperature and subsequent crystallization conditions on the physical form of lactose. AAPS PharmSciTech;3(4). Technical note 1 1–6 (2002).Google Scholar
- 26.Dynamic Mechanical Analysis: A Practical Introduction Kevin P. Menard CRC-Press; 1 edition (December 14, 1997)Google Scholar
- 30.Fox PF, Guinee TP, Cogan TM, McSweeney PLH. Fundamentals of cheese science. USA: Aspen publishers, Inc; 2000.Google Scholar