API Synthesis
What is Active Pharmaceutical Ingredient?
Active Pharmaceutical Ingredient (API) is defined by U.S. Food & Drug Administration as: any substance or mixture of substances intended to be used as the active ingredient in the manufacture of a drug (medicinal) product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or function of the body.
API may exist in the form of liquids, powders, crystals and extracts that obtained by chemical synthesis, plant extraction, or biotechnology and is not taken by patients directly. Only when API is processed into a pharmaceutical preparation, can the product be used for clinical use. The synthesis of APIs is usually a complicated and multi-step process involving numerous chemical transformations and operations on a range of raw materials with different physical and chemical properties. Specialized expertise is needed to achieve the synthesis of these molecules. BOC Sciences with seasoned chemists would provide a comprehensive supply of guaranteed API synthesis service.
Types of Active Pharmaceutical Ingredients
The categorization of Active Pharmaceutical Ingredients (APIs) is a multifaceted endeavor, dependent on their unique chemical architecture and origin. To that end, the triumvirate of API classes is: Synthetic APIs, Biologic APIs, and Natural APIs.
Synthetic APIs, for instance, are purposefully crafted to emulate the intricate design and functionalities of natural compounds, including proteins, enzymes, and hormones. Notably, the pharmaceutical industry widely employs these APIs as they possess a facile manufacturability, longevity, and can be tinkered with to optimize their unique features.
Conversely, Biologic APIs are procured from living organisms, namely cells, tissues, or microorganisms, making their molecules markedly intricate and necessitating unique fabrication techniques, like cell culture, fermentation, and purification.
Lastly, Natural APIs are extracted from organic resources like plants, animals, or minerals. Natural APIs have emerged as potential sources of new drugs, albeit with the notable tradeoff of being less potent and specific than their synthetic or biologic counterparts. Nonetheless, natural APIs exhibit the salient benefit of being more readily obtainable and frequently induce fewer side effects.
Methods of API Synthesis:
Inorganic synthesis
There are certain inorganic molecules can be used as active pharmaceuticals ingredients. Taking the aluminium hydroxide (the synthesis route is displayed as below) as an example, which is a typical inorganic API that reacts with excess gastric acid to reduce the acidity in the stomach, it can significantly relieve the symptoms including ulcer, indigestion and heartburn.
2NaOH + CO2 = Na2CO3 + H2O
NaAl(OH)4 = Al(OH)3↓+NaOH
Organic synthesis
Organic synthetic APIs are produced mainly by basic organic chemicals and underwent a series of organic chemical reactions. Clofarabine, a promising DNA polymerase inhibitor currently in clinical trials, helps the inhibition of DNA repair in leukemic lymphocytes.
Fig. 1. 2-chloroadenine reacts with 1-bromo-2-deoxy-2-fluoro-3, 5-di-O-benzoyl-α-d-ribofuranose
Organic biosynthesis
Organic biosynthesis is an important strategy for API synthesis. The multienzyme total synthesis of the maritimus enterocin wailupemycin bacteriostatic agents and streptomyces are reported in a single reaction vessel from benzoate and malonate substrates (Fig. 2.).
Fig. 2. Biosynthesis primed with acetate via the decarboxylation of malonate (a) and benzoate (b).
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Building blocks are important intermediates for many drugs and have major significance in the discovery and synthesis of drugs. Many important substances and some significant effect of natural drugs and synthetic drugs, such as chlorophyll, heme, and nucleic acid, contain heterocyclic structure.
Owing to chirality is a pivotal factor in the safety and efficacy of many drug products, the production of single enantiomers of drug intermediates has become increasingly important in the pharmaceuticals industry. It has been seen that the increasing awareness of the potential of microorganisms and enzymes derived from the transformation of synthetic chemicals with intermediates.
Impurity profile studies play significant roles in active pharmaceutical ingredient (API) development, which are closely related to the quality, safety and efficacy of drug products.
Metabolites of pharmaceutical compounds are pivotal to comprehending drug metabolism, potential drug interactions, and human drug metabolizing enzymes. The synthesis and purification of considerable amounts of the metabolites provides reliable conclusions regarding the cardiotoxicity of drug metabolites and then pharmacological prevention or treatment of the disease side effects.
Reference materials (reference compounds), established for measuring the quality of analysis, and are critical for any measurement process characterized by a metrologically valid procedure for one or more specified properties.
Overview of our API Development Process
The initial phase of Active Pharmaceutical Ingredient (API) development necessitates the identification of a prospective target molecule that can trigger the desired therapeutic effect, known as Target Identification. This primary stage can be executed using an array of methods, including target-based screening, phenotypic screening, or computer-aided drug design, to name but a few.
Once a target molecule has been pinpointed, the next phase is to increase its efficacy and diminish its toxicity by optimizing its properties, a process referred to as Hit-to-Lead Optimization. Consequently, researchers endeavor to synthesize and assay a sequence of analogs or derivatives of the target molecule to pinpoint the most promising lead compound.
Following the identification of the lead compound, researchers initiate Lead Optimization, whereby the optimization procedure amplifies its pharmacokinetic and pharmacodynamic properties by modifying its chemical structure. Modifications are geared toward enhancing the compound's absorption, distribution, metabolism, and excretion.
Upon the successful completion of Lead Optimization, preclinical development ensues, whereby the optimized lead compound is evaluated in preclinical models to gauge its safety, efficacy, and pharmacokinetics. Animal models, such as rats or mice, are employed to determine the compound's toxicity and effectiveness, and to verify the feasibility of progressing to clinical trials.
Lastly, once the lead compound is deemed safe and effective, API Manufacturing begins, necessitating several manufacturing steps, including synthesis, purification, and characterization, to yield a high-quality API.
BOC Sciences' priority is to provide the highest quality APIs to our customers. Our experts have a wealth of experience in the synthesis of APIs with various starting materials and intermediates. The products will be provided with integrated data packages including chemical purity (GC/MS, HPLC, LC/MS) and concentration (mass spectrometry and NMR). We are pleased to hear from you and looking forward to working with you.
References
- Bauta, W. E., Schulmeier, B. E., Burke, B., Puente, J. F., Cantrell, W. R., Lovett, D., ... & Guo, R. (2004). A new process for antineoplastic agent clofarabine. Organic process research & development, 8(6), 889-896.
- Cheng, Q., Xiang, L., Izumikawa, M., Meluzzi, D., & Moore, B. S. (2007). Enzymatic total synthesis of enterocin polyketides. Nature chemical biology, 3(9), 557.