Granulation pharmaceutical methods

Since the development of the Spansule brand (Smith Kline Beech am) of coated beads and granules in the late 1960s, various dmg product technologies have been developed and patented to achieve extended durations of therapeutic effects. Each of these does so by various mechanisms of control of dmg release from adrninistered dosage forms. Each method has its advantages and disadvantages, a discussion of which is available in the pharmaceutical hterature (see Drug delivery systems) (21). 

The outcome of dissolution tests on pharmaceutical formulations can be influenced by a nnmber of factors including the nature of the excipients and lubricants, blending method and granulation procedure used. When the solubility of the API is not the limiting factor, the compaction pressure used to produce tablets is inversely proportional to their dissolution rate and, as noted in the previous section, directly proportional to the slope of the NIR spectra for intact tablets. Blanco et have developed various approaches for... 

Figure 2 Process flow diagram for the manufacture of a tablet dosage form by wet granulation method. The arrows show the transfer of material into and out of each of the various unit operations. The information in parentheses indicates additions of material to specific unit operations. A list of useful pharmaceutical unit operations is presented in Table 6.

The first direct compression excipient, spray-dried lactose, was introduced in the early 1960s as a filler specifically designed for direct compression processes. Over many years, more direct compression API and excipients, especially diluents and binders, were developed. Since these are now commercially available, design of direct compression formulations is readily possible. However, despite the simplicity of the direct compression process, the pharmaceutical industry still produces most tablets by wet granulation methods.1... 

Slugs or preforms are usually 1 to 2 in. diameter in pharmaceutical manufacture. Suited to granulation of moisture-sensitive materials and those unable to withstand high temperature of drying in wet granulation methods. 

In the standard wet granulating method used to produce tablet feed in the pharmaceutical industry, sigma blade or heavy duty planetary mixers are often employed [12]. These machines may handle 220 or 440 lb (100 or 200 kg) batches and employ 7 to 10 hp (5.2 to 7.5 kW) drives to knead and... 

In the pharmaceutical industry large, often poorly-formed, tablets or slugs are made from fine cohesive powders in large capacity tablet presses and then comminuted to form a granular feed suitable for final tableting [10]. Slugs are typically 1 or 2 in. (2.5 or 5.1 cm) in diameter and perhaps in. (1.3 cm) thick. Results comparable to those accomplished with this piston and die method are also obtained by roll compaction followed by granulation (see Section 2.2). 

Fonner, D. E., Banker, G. S., and Swarbrick, J. (1966), Micromeritics of granular pharmaceutical solids. 1. Physical properties of particles prepared by 5 different granulation methods. /. Pharm. Sci., 55,181. 

Historically, the most common method of drying of pharmaceutical powders has been tray-drying. With this method, wet powder or granulation is placed on paper-lined trays, usually solid or perforated metal, which are then placed directly onto racks in a drying chamber (oven) or onto movable racks, or trucks, that are wheeled into an oven. The heat and low relative vapor pressure of solvent provided by the flow of heated, dry air throughout the chamber provide a driving force for solvent transfer to and subsequent removal from the particle surfaces of the powder. This results in the gradual overall loss of solvent from the bulk powder. 

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