Solid pharmaceutical dosage forms excipients

For the pharmaceutical product development scientist, there is clearly a need for objective information about the practical performance of different excipients and their various grades. In this chapter we set out to bring together the results of some of our ongoing evaluations of the physical and mechanical properties of excipients commonly used for the manufacture of solid oral dosage forms. In this particular article, we have chosen to focus on the fillers that are most commonly used in the manufacture of immediate release tablets microcrystalline cellulose (MCC), lactose, calcium phosphate, and mannitol (1). 

To provide a forum for information exchange of issues relating to solid- and liquid-state characterization of chemical entities, active pharmaceutical ingredients, excipients, and early-phase development of pharmaceutical dosage forms and delivery systems... 

One possibility to improve the structure of compacts is to reduce friction (see also Section 8.2, Fig. 8.3). The addition of lubricants (see also Section 5.1.2) was first introduced in the pharmaceutical industry for the improvement of tablette quality from high speed punch-and-die presses (see below). Even today, lubricants are often a considerable part of the formulation of solid drug dosage forms. Mixed into the entire powder mass such lubricants must be included as inert excipients but always constitute additives that need to be accounted for. Because interparticle friction is normally very little affected by mass lubrication, the amount of lubricants, which, in reality, is meant mostly to reduce wall friction, must be much higher than is commensurate with its effect. Therefore, developments were directed toward the lubrication of only the tool surfaces. For this task, nozzles and solenoid valves which operate reliably in millisecond intervals were used and, later, the lubricant was also electrostatically charged to become attracted by and adhere to the tooling walls [B.42]. 

Uses Pharmaceutical excipient, film-former for enteric coating of solid oral dosage forms, esp. for controlled release of drugs masks unpleasant tastes and odors barrier between incompat. active substances moisture barrier protecting against atmospheric humidity Features Effective barrier to gastric juice protects acid-sensitive drugs releases active at site of action... 

In the present work, such a systematic approach to the physical characterization of pharmaceutical solids is outlined. Techniques available for the study of physical properties are classified as being associated with the molecular level (properties associated with individual molecules), the particulate level (properties pertaining to individual solid particles), and the bulk level (properties associated with an ensemble of particulates). Acquisition of this range of physical information yields a total profile of the pharmaceutical solid in question, whether it is an active drug, an excipient, or a blend of these. The development of a total profile is a requirement for successful manufacture of any solid dosage form. 

A pulsed system, called Time-Clock System, has been developed. It comprises a solid dosage form coated with a hydrophobie surfactant layer to which a water-soluble polymer is attached to improve adhesion to the core [66]. The thickness of the outer layer determines the time required to disperse in an aqueous environment. Following the dispersion of the outer layer, the eore becomes available for dispersion. An advantage is that eommon pharmaceutical excipients can be used to manufacture this system. Studies performed on human volunteers showed that the lag time was not affeeted by gastrie residence time. Furthermore, the dispersion of the hydrophobic film was not influenced by the presence of intestinal digestive enzymes or by the mechanieal aetion of the stomach. 

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