Carbohydrate excipients lactose

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). 

All excipient chemical reactions should be incorporated into the experimental design. For example, drugs that contain primary and secondary amines functionality undergo Maillard reactions with lactose and other reducing carbohydrates such as glucose and maltose under pharmaceutically reasonable conditions.This reaction should be considered during formulation development. Alternative excipients such as mannitol, sucrose, and trahalose, which are not subject to the Maillard reaction, should be used in place of lactose in such cases. 

SoUd-state NMR is a non-desttuctive technique and can be used to look at not only powders but also whole tablets. The spectra of tablets from three different vendors that contain just 5 mg of prednisolone in 100-mg tablets are shown in Fig. 7.15 [56]. Although not shown in Fig. 7.15, excipients do not generally interfere with solid-state NMR analyses because the resonances owing to the most common excipients (carbohydrates, such as lactose, starch, and various forms of cellulose) occur within a narrow range of frequencies (65-80 ppm) while those of the drug substance range from 15 to 240ppm. 

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