Chapter 8. Historical background of pathogenetic therapy

The first information known to science about the use of certain solid pressed dosage forms by mankind for dosing the active substance is presented in the Ebers Papyrus (about 1550 BC), which describes the method of making pills. In addition to Ancient Egypt, this medicinal form was also known in Mesopotamia, and then became widespread in ancient times in Greece and Rome, where the first device for its production was invented. The term «tablet» (Latin tabella) for the designation of the medicinal form was first used in 1608 by Jean de Renou, who used it to name pastilles obtained as a result of pressing (Fig. 8.1).

Fig. 8.1. Jean de Renou (1568–1620) — French doctor and pharmacist, Royal physician

However, until the 19th century, the most common solid oral dosage form were pills, which caused problems when swallowed and were characterized by low stability due to the use of liquid adhesive agents during their production.

The creator of tablets in the modern sense is considered to be the British engineer William Brockedon, who decided to use press when forming the dosage form to completely abandon the introduction of liquid adhesives (Fig. 8.2).

Fig. 8.2. William Brocke­don (1787–1854) — English artist, writer and inventor of the 19th century

On December 8, 1843, Brockedon registered British patent No. 9977 «shaping pills, lozenges and black Lead by Pressure in Dies», in which he described a method for producing «compressed pills» by squeezing a paste located in the matrix with a puncheon that was ерут hit with a hammer. According to Brockedon biographer Liz Wilkinson, judging by the structure of the document, for the inventor, the most important part of this patent was not the dosage forms, but the production of artificial plumbago, with a shortage of which British artists were facing at that time. Nevertheless, in 1844, the text of Brockedon’s patent and samples of potassium bicarbonate tablets derived from it were anonymously delivered to the editorial office of the pharmaceutical Journal and received an approving review from it. However, at the time, this invention did not cause a serious stir, but Brockedon still managed to establish a small production in the UK (Fig. 8.3).

Fig. 8.3. Samples of bicarbonate and potassium chlorate tablets obtained on the basis of the patent of William Brockedon (1843)

The beginning of export deliveries of «pressed pills» of Brockedon gave impetus to the development of new dosage form technology. By 1860, the pills had already become widespread in the United States, but there is evidence that the shipments themselves were organized in earlier years at the request of Commodore Matthew Perry, who met with the pills in London and intended to take them on his expedition to the coast of Japan. In 1864, Jacob Danton established his own production of «pressed pills» in Philadelphia using a manual unit similar to the Brockedon device, which he patented in 1876.

In 1872, in the German Empire, Professor Isidor Rosenthal proposed a replacement for the manual Brockedon device, which was a screw press for the production of tablets. Also in 1872, in the United States, Thomas young introduced the first semi-automatic machine consisting of a matrix and two coaxial punches, from which the upper one was lowered during pressing using an eccentric, and the lower one pushed the formed tablet out of the matrix at the end of the process. In 1874, also in the United States, Joseph McFerran, commissioned by Wyeth, designed a fully automatic rotary tablet press that did not require manual filling of the matrix with tablet mass (Fig. 8.4).

Fig. 8.4. Device of the First McFerran rotary tablet press (1874)

In the McFerran apparatus, a circular arrangement of punches was used, in the matrix of one of which, before pressing, the tableted material was fed through a loading screw. New types of devices marked the beginning of the German-North American struggle for leadership in the field of tablet production, which lasted until the beginning of the 20th century. This competition had the form of a competition of engineers, for whom the first place was the organization of mass production of a new dosage form on an industrial scale, and their quality indicators were only secondary parameters. It was at this time in 1878, instead of «pressed pills», the new dosage form was first called «tablets» (English tablets) — this name appeared on the products of Burroughs, Wellcome & Co, and later was assigned to all similar products of other companies.

Also in 1878, Robert Fuller proposed an alternative method for the production of tablets, in which, instead of pressing a dry mass containing the active substance, the distribution of pasty material was used in prepared forms, from which, after drying, ready-made tablets were squeezed out. As auxiliary substances in this process, water or ethanol were used, in which the active substance was diluted to the desired consistency, mixed with lactose or other fillers. Such tablets were called «trituration», and later found use for active substances in which the use of pressing was unacceptable.

In 1884, German Professor Paul Gerson Unna created a special keratin coating for tablets that allowed them to dissolve in the medium of the small intestine, which was the first example of tablets with modified release (Fig. 8.5).

Fig. 8.5. Unna Paul Ger­son (1850–1929) — German dermatologist