Water spray-dried lactose

Some excipients contain a certain amount of amorphous form such as spray-dried lactose,27 and others are hygroscopic, such as microcrystalline cellulose.28 These excipients will adsorb water, which causes a change in the micro-environment of the formulation. If the drug substance is moisture-sensitive, degradation may occur quickly. Therefore, consider both drug-excipient compatibility and excipient impurity profile in selecting excipients for low-dose drug products. 

Harjunen PI, Lehto VP, Vaelisaari J, et al. Effects of ethanol to water ratio in feed solution on the crystallinity of spray dried lactose. Drug Dev Ind Pharm 2002 28(8) 949-955. 

The Ter (onset) of spray-dried and freeze-dried materials obtained from dynamic DSC analysis are shovm in Figure 44.3 with respective water contents. The decreased with increasing water activities and water contents showing a similar behavior as Tg. T of freeze-dried lactose was higher than T r of spray-dried lactose in the anhydrous state and at all corresponding water contents (Figure 44.3). T for freeze-dried lactose was nearly the same as reported by Roos and Karel (1990) for freeze-dried anhydrous and humidified lactose over various RVP. Crystallization of lactose also occurred differently from differently dehydrated materials. 

Haque, M.K. and Roos, Y.H. Water plasticization and crystallization of lactose in spray-dried lactose/protein mixtures, /. Food Sci., 69, 23, 2004. 

Figure 22 Influence of the amount of lactose or dicalcium phosphate dehydrate (% total weight) on the extrusion forces (N) for mixtures of lactose or dicalcium phosphate dehydrate-Avicel PH 101-water after granulation with a planetary mixer. Each end point is the mean of six values. The SD is lower than 3% for each point. Six different types of lactose were used , a-lactose monohydrate 80 mesh o, a-lactose monohydrate 200 mesh , a-lactose monohydrate 325 mesh , spray dried lactose DCL 11 x, anhydrous P-lactose DCL 21 , anhydrous a-lactose DCL 30. One type of dicalcium phosphate dehydrate was used, a. (From Ref 33.)...

Lactose may be obtained in two crystalline forms a-lactose and P-lactose (in addition to amorphous forms). The alpha form is obtained when water is incorporated into the lattice structure during crystallization (usually by supersaturation below 93.5°C) (5). Alternatively, the beta form does not contain water and exists as a non-hygroscopic and anhydrous form. Amorphous lactose is formed when either the crystallization is rapid or sufficient transient energy is introduced into the crystalline forms (74), i.e., spray drying (75), micronization and milling (76), freeze-drying, and anti-solvent crystallization (77). 

Lactose glass. When a lactose solution is dried rapidly, viscosity increases so quickly that crystallization is impossible. A noncrystalline form is produced containing a- and /J-forms in the ratio at which they exist in solution. Lactose in spray-dried milk exists as a concentrated syrup or amorphous glass which is stable if protected from air, but is very hygroscopic and absorbs water rapidly from the atmosphere, becoming sticky. 

The state of lactose has a major effect on the properties of spray-dried whey powder manufactured by conventional methods, i.e. preheating, condensing to about 50% total solids and drying to less than 4% water. The powder is dusty and very hygroscopic, and when exposed to ambient air it... 

When a lactose solution is dried rapidly, its viscosity increases so quickly that crystallization cannot take place. The dry lactose is essentially in the same condition as it was in solution, except for removal of the water. This is spoken of as a concentrated syrup or an amorphous (noncrystalline) glass. Various workers have shown conclusively that lactose in milk powder (spray, roller, or freeze-dried) is noncrystalline and exists in the same equilibrium mixture of a- and /3-lactose as existed in the milk prior to drying (Zadow 1984). 

Haque, K., and Roos, Y.H. (2005). Crystallization and x-ray diffraction of crystals formed in water-plasticized amorphous spray-dried and freeze-dried lactose-protein mixtures. Car-bohydr. Res. 340,293-301. 

Physical Structure, Water Plasticization, and Crystallization of Spray-Dried and Freeze-Dried Lactose... 

The Tg (onset) values for spray-dried and freeze-dried lactose are shown in Figure 44.2 with corresponding water contents. Tg decreased with increasing... 

Glass-transition temperature (onset) for spray-dried and freeze-dried lactose as a function of water content, determined using DSC during heating at 5°C/min. 

Riickold et al., 2000). This leads to greater or smaller discrepancies between the "official" results for moisture and the water content, depending essentially on the lactose content of the product. For the typical spray-dried milk such as full cream or skimmed milk powder these discrepancies are normally small as the lactose is in most cases amorphous. 

Figure 8.6b shows sorption isotherms for dried skim milk, of which about 50% is lactose. The lactose can remain amorphous when the milk is spray-dried. It can also be made with crystalline lactose, and the normal crystalline form is a monohydrate. The water of crystallization is not available as a solvent, which means that aw is smaller than for amorphous sugar at the same water content, provided the latter is fairly small. At higher water content, the curves cross, and amorphous sugar may crystallize, taking up part of the water. 

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