By Prof. Dr. Hery Suwito, M.Si
Professor of Bioactive Compound Design and Synthesis, Faculty of Science and Technology, Universitas Airlangga

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Import data for Active Pharmaceutical Ingredients (APIs) published by the Ministry of Industry and Statistics Indonesia (BPS) over the past three years amounted to US$443 million (2021), US$509 million (2022), and US$1.27 billion (2023). The primary sources of these imports are China (45%), India (27%), and the United States (8%), with the remaining 20% from other countries. Despite a decrease in import volume in 2023, Indonesia’s dependence on imported APIs remained high—exceeding 90% by 2024.

Not all APIs are imported. A small portion is produced domestically, although not via full synthesis. In most cases, the final synthetic stage is conducted locally, but the precursors used in those final stages are still imported. Therefore, no complete API synthesis from basic domestic raw materials has been established. Moreover, patent costs for using certain production methods continue to burden local manufacturers.

Strategic API Production: The Case of Salicylic Acid

A feasible solution is to produce APIs from domestic raw materials, ideally those that serve dual functions—both as therapeutic agents and intermediates for other pharmaceutical compounds. Another key criterion is that the synthesis methods are patent-free, either because they are in the public domain or have long expired.

A prime example is the production of salicylic acid, which can be synthesized using the Kolbe-Schmitt reaction, involving phenol, sodium hydroxide, and carbon dioxide (CO₂). Phenol is an aromatic alcohol derived from benzene, a byproduct of petroleum. Indonesia already has four phenol-producing companies with a combined annual capacity of 125,250 tons.

This production method diversifies phenol applications beyond existing uses, tapping its potential as a pharmaceutical precursor. Indonesia also boasts eight sodium hydroxide producers, generating a total annual capacity of 1,306,000 tons. Meanwhile, PT Pupuk Kujang is a major producer of liquid CO₂, obtained from excess gas during fertilizer production, with a capacity of 50,000 tons/year and 99.9% CO₂ purity.

Kolbe-Schmitt Reaction Process

In the Kolbe-Schmitt process, phenol reacts with sodium hydroxide to form sodium phenoxide while water is evaporated. Carbon dioxide is then bubbled through the reaction vessel under 100–130°C temperature and 5–7 atm pressure. The resulting sodium salicylate is neutralized with hydrochloric or sulfuric acid, precipitating salicylic acid with a purity exceeding 90%.
This process was patented in 1860 by German chemists Hermann Kolbe and Rudolph Schmitt and is now public domain.

Applications and Derivatives of Salicylic Acid

Medically, salicylic acid is used to treat skin conditions such as eczema, corns, calluses, and warts, and serves as a base for synthesizing other drugs:

• Salisylamide – an analgesic and antipyretic; often combined with caffeine in cold remedies.

• Salsalate – a dimer of salicylic acid used to treat chronic inflammatory diseases like rheumatoid arthritis and osteoarthritis, with reduced gastric irritation compared to aspirin.

• Sulfasalazine – used to treat inflammatory bowel disease, rheumatic arthritis, and as an immunomodulator.

• Diflunisal – an analgesic and anti-inflammatory agent.

Producing salicylic acid locally is a strategic starting point toward API self-reliance. As both a therapeutic compound and intermediate for other pharmaceuticals, it offers a viable model for building domestic pharmaceutical resilience—economically and scientifically.

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Reposted by admin from source: “Jalan Panjang yang Belum Usai: Menuju Kemandirian Produksi Obat di Indonesia” | Jalan Panjang yang Belum Usai: Menuju Kemandirian Produksi Obat di Indonesia | jurnalindonesia.net