A-lactose monohydrate

WjU 4-0-/ -D-Galactopyranosyl-a-D-glucopyranose, monohydrate (a-lactose, monohydrate) LACTOS01, 10 30 453... 

Ludipress a-Lactose monohydrate, povidone, crospovi-done BASF... 

Flow behavior of powders is also of interest in direct compression. It is generally accepted that the flow rate initially increases with particle size, achieves a maximum in the range of 100-400 /um, and then decreases [85]. An excipient that has been well characterized is lactose, which undergoes particle fragmentation when compacted. For a-lactose monohydrate, it has been shown that the... 

The Storage to Initial Ratio of two tablet parameters crushing strength (S) and disintegration time (D) were measured for a combination of one filler-binder (a-lactose monohydrate) and one disintegrant (rice starch), at three concentration levels. 

The used tablet ingredients were a-lactose monohydrate (Ph.Eur grade, 100 mesh), rice starch (Ph.Eur. grade) and magnesium stearate (Ph.Eur. grade). Before use the magnesium stearate was sieved through a 210 im sieve. Prior to use, the materials were stored at 20 1 °C and 45 5% relative humidity (RH) for at least one week. 

Just as may be expected, the initial disintegration time of a-lactose monohydrate/starch tablets is influenced by the starch concentration. The compression load level has a small effect on the initial disintegration time. The effect of the concentration is influenced by the level of the compression load. 

Tablets were prepared either with an insoluble (dicalcium phosphate dihydrate), a soluble (6-lactose) or a moderately soluble filler-binder (a-lactose monohydrate). As a disintegrant four different starches (com, rice, potato and tapioca) were used. As a comparison the effect of two super-disintegrants (crospovidone and sodium starch glycolate) was studied. The disintegrants were added at two concentration levels. The compression load was adjusted in order to obtain tablets with comparable initial cmshing strengths.

Figure 8.3a Storage to Initial Ratio of crushing strength (SIR(S)) of a-lactose monohydrate/tapioca starch tablets (20% w/w disintegrant) as a function of the storage time...

Native starches are used as disintegrants, diluents, and wet binders. However, their poor flow and high lubricant sensitivity make them less favorable in direct compression. Different chemical, mechanical, and physical modifications of native starches have been used to improve both their direct compression and controlled-release properties (Sanghvi, 1993 van Aerde and Remon, 1988). Schinzinger and Schmidt (2005) used potato starch as an excipient and compared its granulating behavior with a-lactose-monohydrate and di-calcium phosphate anhydrous in a laboratory fluidized bed granulator using statistical methods. 

Coprocessing of a-lactose monohydrate with cornstarch helped in improving its compressibility, and provided dual benefits of enhanced binding capacity and better disintegration potential, the attributes associated to starch (48). This effect was a result of binding of small starch particles together with a-lactose monohydrate crystals into compound particles. 

Figure 6.3. Tomahawk crystal of a-lactose monohydrate. (From Nickerson 1974.)...

It has been demonstrated in the laboratory that by careful manipulation of alcohol concentration, amorphous lactose high in the /3 anomeric form could be precipitated (Majd and Nickerson 1976 Ross 1978A Olano and Rios 1978). Parrish et al. (1980B) have formed /3-lactose from stable forms of anhydrous a-lactose and have prepared /3-lactose from a-lactose monohydrate with potassium methoxide (1979B). None of these processes have been commercialized. 

Other approaches use Laser-Raman spectra to differentiate five conformational states of lactose, including a-lactose monohydrate, /3-lactose, and lactose glass (Susi and Ard 1974). Differential thermal analysis has also been used to measure the concentration of crystalline lactose, especially a-lactose hydrate (Ross 1978B). The specialized equipment required by these procedures may limit their use. 

Parrish, F. W., Ross, K. D. and Simpson, T. D. 1979B. Formation of /3-lactose from a-and /3-lactose octaacetates, and from a-lactose monohydrate. Carbohydr. Res. 71, 322-326. 

Parrish, F. W., Sharpies, P. M., Hoagland, P. D. and Woychik, J. H. 1979, Demineralization of cheddar whey ultrafiltrate with thermally regenerable ion-exchange resins Improved yield of a-lactose monohydrate. J. Dairy Sci. 44, 555-557. 

Seifert, H. and Labrot, G. 1961. About the structure of a-lactose-monohydrate (milk sugar). Naturwissenschaft 48, 691. 

The Raman spectra of a-lactose monohydrate, /1-lactose in the crystalline state, a-lactose-/3-lactose mixture, and equilibrated lactose in aqueous solution have been investigated.186 It was found that the spectra are very sensitive to small structural changes, and this suggested that Raman spectroscopy should be used as a method for identification of closely related isomers. 

Scheme 22.—Radical Chain-reactions in Crystalline a-Lactose Monohydrate.

Savolainen et al. investigated the role of Raman spectroscopy for monitoring amorphous content and compared the performance with that of NIR spectroscopy [41], Partial least squares (PLS) models in combination with several data pre-processing methods were employed. The prediction error for an independent test set was in the range of 2-3% for both NIR and Raman spectroscopy for amorphous and crystalline a-lactose monohydrate. The authors concluded that both techniques are useful for quantifying amorphous content however, the performance depends on process unit operation. Rantanen et al. performed a similar study of anhydrate/hydrate powder mixtures of nitrofurantoin, theophyllin, caffeine and carbamazepine [42], They found that both NIR and Raman performed well and that multivariate evaluation not always improves the evaluation in the case of Raman data. Santesson et al. demonstrated in situ Raman monitoring of crystallisation in acoustically levitated nanolitre drops [43]. Indomethazine and benzamide were used as model... 

Such small particles usually are generated by air-jet micronization and less frequently by controlled precipitation or spray drying. As bulk powder, they usually tend to be very cohesive and exhibit poor flow and insufficient dispersion because of large interparticle forces such as van der Waals and electrostatic forces (Zeng et al. 2001 Podczeck 1998 Hickey et al. 1994). The control of sufficient powder flow and deaggregation (dispersion) is thus of utmost importance to ensure efficient therapy with a dry-powder aerosol. Two different formulation approaches are used currently in marketed DPI preparations to fulfill the requirements. Most often, coarse particles of a pharmacologically inactive excipient, usually a-lactose monohydrate, are added that act as a carrier and provide sufficient powder flow to the mixture. Other carbohydrates, amino acids, and phospholipids have been suggested frequently (Crowder et al. 2001). 

Other examples of the use of microcalorimetry to study drug-excipient compatibility in the solid state are provided by Selzer et al. (30), who studied the interaction between a solid drug and a range of excipients [including potato starch, a-lactose-monohydrate, microcrystalline cellulose (MCC), and talc] and Schmitt (31) who used water slurries instead of humidified samples. 

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