A Long Way to Go: Toward Drug Production Independence in Indonesia
By: Prof. Dr. Hery Suwito, M.Si
DATA on imports of Raw Materials for Medicines (BBO) released by the Ministry of Industry and the Central Bureau of Statistics (BPS) in the last three years are US$443 million (2021), US$509 million (2022), and US$1.27 billion (2023). The main countries importing the raw materials are China (45%), India (27%), and the United States (8%), with the remaining 20% coming from other countries. Despite a decrease in import volume in 2023, BBO import dependency remains high, reaching more than 90% in 2024.
The fulfillment of BBO is not all imported. A small portion of these drugs are already produced in Indonesia, although not through total synthesis, meaning that BBO is produced from simple chemicals. The production process is usually carried out at the final stage of the reaction, while the raw materials needed for the synthesis of the final stage of the reaction are still imported.
Thus, there has been no synthesis of medicinal raw materials from simple basic ingredients derived from domestic production. In addition, there are additional production costs that must be paid, namely the patent costs of the production methods used.
One of the solutions that can be offered to solve the problem of BBO production is to produce BBOs made from domestic ingredients, as well as those that have dual functions, namely useful as drugs and as intermediates for producing medicinal ingredients with other activities.
Furthermore, the production method of the material is free of patent fees, which can be obtained from a production method that has exceeded the limit for paying patent fees (a patent has been registered for a long time).
A simple BBO production that meets these criteria is salicylic acid production. Salicylic acid can be produced using the Kolbe-Schmitt reaction from phenol and sodium hydroxide as raw materials, followed by the addition of carbon dioxide (CO2) gas.
Phenol is an aromatic alcohol obtained from benzene, while benzene can be obtained from petroleum. There are 4 companies that produce phenol in Indonesia with a production capacity of 125,250 tons per year.
If so far phenol has not been widely used for the production of pharmaceutical materials, this breakthrough is an effort to diversify other phenol applications. As for sodium hydroxide, Indonesia has a production capacity of 1,306,000 tons per year from 8 chemical companies.
One of the main producers of liquid carbon dioxide in Indonesia is PT Pupuk Kujang, which is produced by utilizing excess gas from fertilizer production, with a production capacity of 50,000 tons of liquid CO2 per year, with the purity of CO2 produced up to 99.9%. This data shows that the basic materials needed to produce salicylic acid can be obtained domestically.
In the salicylic acid production process using the Kolbe-Schmitt reaction, the first step is to react phenol with sodium hydroxide to form sodium phenoxide, while the water formed is evaporated. The next stage is to flow CO2 gas into the reaction vessel, and the reaction mixture is heated at a temperature of about 100-1300C and a pressure of 5-7 atm. The sodium salicylate salt formed is then neutralized using strong acid (hydrochloric acid or sulfuric acid), so that the desired salicylic acid precipitates.
After filtering, salicylic acid with a purity of more than 90% will be obtained. The Kolbe-Schmitt reaction was patented by two German scientists, Hermann Kolbe and Rudolph Schmitt in 1860. Therefore, this patent has expired and can be used freely.
In the medical field, salicylic acid is commonly used for the treatment of skin problems (removing dead skin layers, calluses, warts and eczema), reducing inflammation, and used as a raw tire for other drugs.
The following are other drugs made from salicylic acid. Salicylamide is a salicylic acid derivative that is used as an analgesic (pain reliever), and antipyretic (fever reducer) drug. The combination of salicylamide with caffeine is used as a cold or flu medicine.
Salsalate is a salicylic acid dimer that is usually used as a chronic anti-inflammatory drug, especially rheumatoid arthritis and osteoarthritis. It has the advantage of causing less gastric irritation than aspirin.
Next is sulfasalazine, which is commonly used as an inflammatory bowel drug, rheumatic arthritis, and immunomodulator. The last is diflunisal, which is commonly used as an analgesic (pain reliever), and anti-inflammatory drug.
It can be concluded that the selection of salicylic acid production can be used as the initial stage of drug production made from domestic raw materials. In addition, salicylic acid is also an intermediate material that becomes the raw material for the production of other salicylic acid-based drugs. (The author is a Professor of Design and Synthesis of Bioactive Compounds, Faculty of Science and Technology – Universitas Airlangga)
Republished by admin from the source: A Long Way to Go: Toward Independence of Drug Production in Indonesia
