Lactose crystallinity

Diluent Bulking agent to adjust tablet Lactose, crystalline cellulose, dicalcium... 

Both maltose and lactose, being reducing sugars, give osazones which differ from one another and from glucosazone in crystalline form. Sucrose (G-r-r-F), having no potential aldehyde or ketone grouping, does not form an osazone. 

The approximate times of osazone formation in minutes are given in Table 111,139. The product from mannose is the simple hydrazone and is practically white. Arabinose osazone separates first as an oil, whilst that from galactose is highly crystalline. Lactose and maltose give no precipitate from hot solution. 

X-ray diffraction studies are usually carried out at room temperature under ambient conditions. It is possible, however, to perform variable-temperature XPD, wherein powder patterns are obtained while the sample is heated or cooled. Such studies are invaluable for identifying thermally induced or subambient phase transitions. Variable-temperature XPD was used to study the solid state properties of lactose [20], Fawcett et al. have developed an instrument that permits simultaneous XPD and differential scanning calorimetry on the same sample [21], The instrument was used to characterize a compound that was capable of existing in two polymorphic forms, whose melting points were 146°C (form II) and 150°C (form I). Form II was heated, and x-ray powder patterns were obtained at room temperature, at 145°C (form II had just started to melt), and at 148°C (Fig. 2 one characteristic peak each of form I and form II are identified). The x-ray pattern obtained at 148°C revealed melting of form II but partial recrystallization of form I. When the sample was cooled to 110°C and reheated to 146°C, only crystalline form I was observed. Through these experiments, the authors established that melting of form II was accompanied by recrystallization of form I. 

Lactose is normally encountered as a component of any skim milk that is used in bakery products. Small quantities of crystalline lactose are sometimes used in baked goods. If a product is made with too much lactose then a metallic taste appears. The amount of lactose that can be consumed without this taste appearing varies between individuals. 

This particular trimethylglucose is unique in that it was separated in crystalline form from the hydrolyzates of the methyl ethers of several naturally-occurring glucose polymers almost two decades before it was synthesized from glucose. These natural sources, which still furnish the most convenient routes for the preparation of 2,3,6-trimethyl-D-glucose, include maltose,124-128 cellobiose,127,128 lactose,122-181 starch,71,182 glycogen,188,184 cellulose,185-187 and lichenin. 188,189 The literature pub-... 

Lactose.—The whey is concentrated to a small volume on a ring burner which causes almost complete precipitation of the albumin. The mixture is filtered through linen, and the filtrate is again concentrated until lactose separates. When the mixture is cold the crude crystalline sugar is collected by filtration through linen on a Buchner funnel and dried. A second portion of lactose is obtained by further concentration of the mother liquor—this time on the water bath. Yield of crude material 70-75 g. 

Small amounts of surfactants may be used to prevent aggregation of proteins and may enhance the refolding process when the dried protein dissolves. Buffers may also help to prevent aggregation of the dissolved drug. Similarly, polymers may be used as aggregation inhibitors or to form matrices. Chan et al. [86] prepared crystalline powders of recombinant human deoxyribonuclease with high fractions of sodium chloride. These powders were formulated as adhesive mixtures on lactose and mannitol and showed improved aerosolization behaviour compared to the pure protein. 

H.V, Van Kamp, G.K. Bolhuis and C.F. Lerk, Effect of both lubrication and addition of disintegrants on properties of tablets prepared from different types of crystalline lactose. Act. Pharm. Suec., 23 (1986) 217. 

Figure 13. Screw extruders extrude poorly when the proportion of water soluble compounds, such as mannitol or lactose, reaches 50% or higher. Such formulations are better extruded with low-shear basket extruders (28). As the solubility increases from 5% to 30%, the percent of water needed for extrusion could decrease by up to 25%. This has implications for scale-up, as early lots of drug substance may have a different crystallinity or solubility profile than pilot lots.

Riepma KA, Lerk CF, De Boer AH, Bolhuis GK, Kussendrager KD. Consolidation and compaction of powder mixtures. I. Binary mixtures of same particle size fractions of different types of crystalline lactose. Int J Pharma 1990 66(l-3) 47-52. 

Given the complexity that arises from the multitude of interacting variables associated with DPI systems, there are very few excipients that have been incorporated into DPI formulations. Examples of commonly marketed products are listed in Table 2. Lactose has many benefits including a well-established safety profile, low cost, and wide availability. Physicochemical properties of lactose are also relatively desirable from a DPI formulation standpoint smooth surfaces, crystalline, and moderate flow properties. However, lactose may not be suitable for some active... 

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). 

Partly delactosed whey is produced by concentrating cheese whey or casein whey sufficiently to exceed the solubility limit of lactose, followed by cooling, seeding with lactose crystals and removal of the crystalline lactose. The resulting liquor fraction is recovered and dryed. 

Some properties of a- and /1-lactose are summarized in Table 2.3. Mixed a// crystals, e.g. a5/ 3, can be formed under certain conditions. The relationship between the different crystalline forms of lactose is shown in Figure 2.8. 

Lactose normally occurs naturally in either of two crystalline forms— a-monohydrate and anhydrous /3—or as an amorphous glass mixture of a- and /3-lactose. Several other forms may be produced under special conditions. 

Crystalline Habit. a-Lactose hydrate crystals are observed in a wide variety of shapes, depending on conditions of crystallization. The principal factor governing the crystalline habit of lactose is the precipitation pressure, the ratio of actual concentration to solubility (Herrington 1934A). When the pressure is high and crystallization is forced rapidly, only prisms form. As precipitation pressure lessens, the dominant crystal form changes to diamond-shape plates, then to pyramids and tomahawks, and finally, in slow crystallization, to the fully developed crystal. These types of crystals are illustrated in Figure 6.2. 

Figure 6.2. The crystalline habit of lactose a-hydrate. (A) Prism, formed when velocity of growth is very high. (B) Prism, formed more slowly than prism A. (C) Diamond-shaped plates transition between prism and pyramid. (D) Pyramids resulting from an increase in the thickness of the diamond. (E) Tomahawk, a tall pyramid with bevel faces at the base. (F) Tomahawk, showing another face which sometimes appears. (G) The form most commonly decribed as fully developed. (H) A crystal having 13 faces. The face shown in F is not present. (I) A profile view of H with the tomahawk blade sharpened. (From van Krevald and Michaels 1965. Reprinted with permission of the Journal of Dairy Science 48(3), 259-265.)...

In dairy products, crystallization is more complex. The impurities (e.g., other milk components), as far as lactose is concerned, may interfere with the crystalline habit. As a result, the crystals tend to be irregularly shaped and clumped, instead of yielding the characteristic crystals obtained from simple lactose solutions. In some instances, the impurities may inhibit the formation of nuclei and thus retard or prevent lactose crystallization (Nickerson 1962). 

Riboflavin also may adsorbed on growing lactose crystals and alter the crystalline habit. Since it is naturally present in the whey from which lactose hydrate is made and is present in all dairy foods, its influence on lactose crystallization may be of special interest. Adsorption is dependent upon concentration of riboflavin in solution, on degree of lactose supersaturation and on temperature (Leviton 1943, 1944 Michaels and Van Krevald 1966). No adsorption occurs below a certain minimum (critical) concentration of riboflavin (2.5 uglml), but adsorption increases linearly with riboflavin concentration above this critical level. Increasing the temperature of crystallization results in reduced riboflavin adsorption. Adsorption is favored at lower supersat-... 

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