Historical Background

The concept of producing dosage units by molding is not new. Molded tablets or tablet triturates were introduced by Fuller in 1878 as unit oral dosage forms; a moistened powder comprising drug and excipients was pressed into a cavity, extruded, and dried (Fig. 12.1). Suppositories are also manufactured by casting a molten mass in a mold and allowing it to solidify by cooling (Fig. 12.2). Simple tablet and suppository molding techniques and equipment were prevalent in the nineteenth century. Earlier manufacture involved mixing with a spatula and "hand-rolling" on a glass plate [1]. Such "drug delivery" approaches did not encompass concepts of modifying release or otherwise enhancing drug performance. They were simply a means of providing an accurate dose of medication in as "user-friendly" a form as was possible at the time.

Manual and automatic machinery was developed for more efficient manufacture of molded tablets and suppositories, but as better unit dose presentations became ft ^

Fig. 12.1 Molded tablet or tablet triturate mold. The cavities plate is placed on the glass plate, the moistened mass is forced into the cavities and then the pegs plate is used to extrude the tablets ft ^

Fig. 12.1 Molded tablet or tablet triturate mold. The cavities plate is placed on the glass plate, the moistened mass is forced into the cavities and then the pegs plate is used to extrude the tablets

Fig. 12.2 Suppository form or mold. The molten mass is cast into the mold (held closed with the screws), the mass is allowed to solidify, the mold is opened by loosening the screws and the suppositories are ready for insertion

available (e.g. tablets and capsules) there was no significant evolution of technologies for pharmaceutical manufacture of "molded" dosage forms. However, as techniques for synthesizing different "plastic" materials were invented there were concomitant developments of technologies to process these to product forms. In 1855, Alexander Parkes developed a synthetic replacement for ivory made from cellulose treated with nitric acid and a solvent. Cellulose nitrate could be dissolved in alcohol and hardened into a transparent elastic material that could be molded to a desired shape or form when heated. Many other materials were subsequently invented. In 1868, John Wesley Hyatt developed a plastic, which he named "celluloid" that could be readily processed into product forms. He patented the first injection molding machine in 1872 [2], which was based on a plunger forcing the plastic through a heated cylinder into a mold.

The first plastic based on a synthetic polymer was made from phenol and formaldehyde (Bakelite) in 1909 by Leo Hendrik Baekeland [3]. In 1946, James Watson Hendry built the first screw injection molding machine (the screw is now termed the extruder), which afforded precise control over speed of injection and quality of product. It also allowed materials to be mixed before injection, for instance, colored or recycled plastic could be added to virgin material and mixed thoroughly before being injected. Today, screw injection technology is incorporated in the majority of machines. In the 1970s, Hendry developed the first gas-assisted injection molding process, permitting the manufacture of complex, hollow articles that cooled quickly. This greatly improved design possibilities as well as product strength and finish, while reducing production time, cost, weight, and waste [4].

For the production of objects made of plastic, thermoforming (when the plastic can be repeatedly melted and solidified) or thermosetting (when the plastic irreversibly cures) technologies were developed. Other technologies included calendaring, film casting, film blowing, extrusion, and injection. Many of these are used in the pharmaceutical industry, but for packaging or making patches and plasters and not

-Injection Unit-x-Clamping unit-

Fig. 12.3 Schematic section of an injection molding machine. The numbers in the picture correspond to the numbers in parenthesis in the text [#]

-Injection Unit-x-Clamping unit-

Fig. 12.3 Schematic section of an injection molding machine. The numbers in the picture correspond to the numbers in parenthesis in the text [#]

usually in dosage form design. However, injection molding has been used to manufacture implants [5], while screw extrusion and calendaring techniques are gaining momentum in melt-granulation. The next section describes equipment and mode of extrudate formation, as it pertains to dosage forms as well as other forms of product manufacture.

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