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| Basic properties | ||||
| Chemical and biochemical properties | ||||
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Lactose is very stable from a chemical point of view. Except for some special cases, it has no tendency to react with the active ingredient or other components of a formulation. Some remarks on the chemical properties of lactose are useful, however. The low hygroscopicity of lactose supports its virtual chemical inertness. Most chemical reactions of lactose occur noticeably only in aqueous environments. Because lactose has no tendency to attract moisture, water in dry lactose preparations is normally not present in amounts sufficient for chemical reactions to proceed at a noticeable speed. The water of crystallisation is bound so tightly in the crystal lattice of the lactose that it is chemically inert. Dehydration and pyrolysis At temperatures above 100ºC, α-lactose monohydrate gradually loses its water of crystallisation. At 140ºC, loss of crystal water is completed. The loss of water of crystallisation is accompanied by loss of the crystalline structure of the lactose – the lactose becomes amorphous. Further heating of lactose to higher temperatures causes the lactose to decompose. This process is called pyrolysis. The primary reaction products of pyrolysis tend to polymerise, resulting in brown and black macromolecules. Eventually, the lactose becomes black on heating. Maillard reaction In aqueous solution, lactose, as all reducing sugars (e.g. glucose, galactose, maltose, maltodextrines), tends to react with compounds containing primary amino-groups. Such compounds are proteins and peptides, for example. This reaction is called the Maillard reaction. The chemical pathways of the Maillard reaction are very complicated and will not be discussed further in this section. High temperature and high pH (high alkalinity) favour a quick completion of the reaction. At an advanced stage, yellow and brown polymers are formed, which ultimately turn the reaction mixture black. Purified lactose, even of pharmaceutical grades, still contains traces of proteinaceous matter. These are the reason why a Maillard reaction cannot be excluded completely even from some dry lactose preparations. However, the Maillard reaction requires some unbound water, although very little may suffice. Here again the low hygroscopicity of lactose proves favourable. α-lactose monohydrate and roller-dried lactose have no tendency to adsorb moisture. In addition, they have a sufficiently low moisture content to prevent the Maillard reaction to occur. Even over periods of years no change in colour is noticeable. Spray-dried lactose, however, being somewhat more hygroscopic, has some tendency to discolour slightly at long storage times. The somewhat higher free moisture content of spray-dried lactose favours discolouration. Formulating lactose with drugs of a protein or peptide character should pose no problems for drug stability, provided the free moisture content of the formulation can be kept very low. Fermentation As mentionedbefore, lactose is a carbohydrate and as such a suitable substrate for micro-organisms such as bacteria, yeasts and moulds. Controlled use of this phenomenon is made in several industrial fermentation processes where lactose is used as the carbon source. Uncontrolled fermentation of lactose, i.e. microbial spoilage of the lactose product, is of course highly undesirable. Here again, the low hygroscopicity of lactose adds to its microbial stability . Micro-organisms require moisture. Storage of lactose under dry and cool conditions will prevent microbial spoilage. |
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