The Basic Concepts of Active Pharmaceutical Ingredients

What is an active pharmaceutical ingredient?

An Active Pharmaceutical Ingredient (API) is the chemical substance contained in a pharmaceutical, which is responsible for its therapeutic effect. However, APIs generally cannot be used directly as medicine taken by patients. APIs need to be formulated into dosage forms with the addition of pharmaceutical excipients. There are more than 2,000 APIs worldwide up to now. Only a few pharmaceutical companies can produce their own APIs, but no one can produce all the APIs they need.

The quality of an API determines the quality of the pharmaceutical formulation. Countries around the world have developed strict pharmacopoeia standards and quality control methods for APIs.

What is an Intermediate?

An intermediate is a chemical substance produced during the API manufacturing process. Intermediates need further reactions or processing to be transformed into the active pharmaceutical ingredient. The FDA (U.S. Drug Administration) requires intermediates to be registered.

Types of APIs

APIs can be categorized into two major types based on their source: synthetic APIs and natural APIs.

Synthetic APIs

A synthetic API refers to a product with a certain therapeutic effect obtained by means of a chemical reaction under specific conditions. Synthetic APIs can be further divided into inorganic APIs and organic APIs.

Inorganic APIs

Inorganic APIs are inorganic compounds, such as Aluminum Hydroxide for treating stomach and duodenal ulcers.

Examples of Inorganic APIs

  • Sodium Hydroxide
  • Copper Oxide
  • Magnesium Hydroxide
  • Sodium Bicarbonate
  • Potassium Iodide

Organic APIs

Organic APIs are mainly obtained through a series of organic chemical reactions, such as Aspirin and Chloramphenicol. In terms of variety and market, organic APIs far surpass inorganic APIs.

Examples of Organic APIs

  • Pranoprofen
  • Antipyrine
  • Eletriptan
  • Sulfadiazine

Natural APIs

Natural APIs are the biologically active components in medications that are derived from natural sources. Natural APIs can also be classified into biologic APIs and phytochemical APIs based on their source.

Biologic APIs

Biologic APIs are usually produced using biotechnological methods and are characterized by their complex structures and high molecular weight. The manufacturing of antibiotics is primarily based on microbial fermentation process.

Examples of Biologic APIs

  • Erythromycin
  • Calicheamicin
  • Lincomycin hydrochloride
  • Oxytetracycline

Phytochemical APIs

Phytochemical APIs refer to a class of chemical substances with clear physiological activity obtained by extraction and separation from medicinal plants. Most of the phytochemicals are chemically pure substances, which can be processed as raw materials into drugs for clinical application.

Examples of Phytochemical APIs

  • Allicin
  • Anthocyanins
  • Monoterpene
  • Lutein

Manufacturing Process of APIs

The manufacturing process of Active Pharmaceutical Ingredients involves several stages to produce the desired compounds with high purity and efficacy. The process varies depending on whether the API is a small molecule or a biologic, but here is an outline of the typical steps:

  • Research and Development

    Identify a new chemical entity or biological entity with potential therapeutic effects. Conduct extensive preclinical testing to assess the drug candidate’s efficacy, toxicity, and pharmacokinetics.

  • Process Development

    Determine the most efficient and cost-effective synthetic route or production method. Optimize the process conditions to maximize yield and purity. Transition the process from laboratory scale to pilot scale.

  • Synthesis For Small Molecules

    Conduct a series of chemical reactions to transform raw materials into intermediates and finally into the API. Use catalysts to speed up reactions or improve yields if needed. Extract and isolate intermediate compounds at various stages.

  • Fermentation or Bioreaction for Biologics

    Fermentation involves the growth of microorganisms such as bacteria, yeast, or fungi to produce biologics. It is especially useful for producing products like antibiotics, insulin, and other therapeutic proteins.

  • Purification

    Separate the crude APIs from the reaction mixture or fermentation broth. Utilize techniques such as crystallization, distillation, chromatography, and filtration to achieve high purity.

  • Quality Control

    Conduct rigorous tests to ensure the API meets specified purity, potency, and safety standards.