API Custom Synthesis | Contract Manufacturing Services

Introduction

What is API?

Active Pharmaceutical Ingredients (APIs) are the biologically active components of a pharmaceutical drug that produce suitable therapeutic effects. It is the key ingredient of a finished pharmaceutical product. These are pure substances or a mixture of substances combined with excipients. They are found in diverse forms from powder to crystals. 

 Types of APIs 

• Small Molecule APIs: These chemically synthesized APIs comprise 100-200 atoms and a molecular mass of less than one kilodalton. They can easily pass across cell membranes and act on certain proteins and other bioactive molecules. Examples include Vitamin C, Steroids, Aminoglycoside, Beta-lactam, and Acetaminophen.
• Biological APIs: Biologic APIs are large, complex molecules extracted from living organisms, such as proteins, antibodies, and vaccines. These are helpful in the treatment of diabetes, cancer, autoimmune disorders, and oncological disorders. Examples include Vaccines, Insulin, and Monoclonal Antibodies.
• Peptide APIs: Peptide APIs are complex structures of two or more amino acids that imitate natural peptides or proteins. They are highly selective and effective, accumulating low body tissue levels and reducing toxicity. However, these drugs are short-lived. They offer targeted treatments for conditions like metabolic and oncological disorders.
• Polymer API: These large molecules comprise repeating units of smaller molecules that are utilized to deliver drugs or act as the active ingredient themselves, enhancing the stability and potency of medications.
• High-Potency APIs (HPAPIs): HPAPIs are greatly effective and pharmacologically active ingredients at very low doses, helpful in the treatment of diverse conditions. These require specific handling and manufacturing processes due to their efficacy and potential toxicity. 
• Natural APIs: These APIs are extracted from natural sources such as plants, animals, and microorganisms. While less common than synthetic APIs, these are still used in several essential medications such as insulin, penicillin, morphine, codeine, and quinine.
• Synthetic APIs: Synthetic APIs are widely used in several medications, and are chemically synthesized in the laboratory to imitate natural products. Furthermore, they are easy to manufacture and can be modified to enhance their features. Examples include acetylsalicylic acid(API in aspirin), paracetamol, and Ibuprofen (nonsteroidal anti-inflammatory drug).

What is Custom Synthesis?

Custom synthesis is a unique service offered by chemical and pharmaceutical companies, where molecules are precisely designed and manufactured for clients. Unlike commercial generic drugs, custom synthesis involves tailored production methods to ensure the desired purity, quality, and quantity of a compound. 

There are many important characteristics to look for that make custom synthesis a vital element of the pharmaceutical industry:

• Molecular Design with a Purpose: Expertise generates new molecules or modifies preexisting ones to attain certain therapeutic properties or meet clients’ requirements. This involves deeply comprehending the fundamentals of chemistry and details. 
• Quality Control and Assurance: It’s essential to ensure the safety and efficiency of the product throughout the synthesis process via careful testing and analysis, to ensure the product meets the rigorous quality standard. 
• Adaptability: Flexibility is essential to bring out a new medicine to the market, custom synthesis can be scaled up to produce larger quantities of a compound as needed, supporting clinical trials and commercialization.

Considerations Before Undertaking API Synthesis

Several essential points are to be evaluated before initiating API synthesis to ensure productive and efficient procedures. These factors encompass regulatory conditions, cost-effectiveness, safety rules, environmental influence, and adaptability. 

• Regulatory requirements: Different countries have specific regulations governing API synthesis including Good Manufacturing Practices (GMP), documentation requirements, and quality control standards. Comprehending and following these regulations is vital. Non-compliance will create certain delays, financial penalties, and damage to reputation. 
• Personal and environmental safety: API synthesis frequently comprehends operating hazardous substances therefore effective rigid safety measures such as proper ventilation, protective gadgets, and emergency response methods are crucial. Adhering to protocols protects human health and also ensures regulatory compliance. 
• Cost-effectiveness: API synthesis can be costly. There are several cost-efficient factors to be considered such as equipment investments, labor expenses, raw material costs, and potential scale-up challenges. Optimizing and analyzing the synthesis route and cost-cutting schemes reduces the cost and enhances the profitability.
• Environmental Impact: API synthesis can produce waste products and drain a significant volume of energy and water. The pharmaceutical industries are accountable and should be more eco-friendly by executing sustainable actions like energy efficiency, waste reduction, and water conservation, which are critical for environmental protection. 
• Adaptability: Evaluating expandability initially in the progression stage assists in averting delays and obstructions in future production. For making certain sustainable supply chains and fulfilling market demands, API productions should be amplified by considering the accessibility of raw materials and equipment, the ability for process enhancement, and the resilience of the synthesis process. 

By precisely analyzing these elements you can make informed decisions about API synthesis, reduce possible risks, and establish a profitable and accountable development procedure. 

Steps Involved in API synthesis

• Raw Material Acquiring: Our experts at Macsen precisely select top-grade raw materials from trusted manufacturers ensuring their efficacy, purity, and integrity through vigilant and precise quality control measures. 
• API design: We draft the API molecules according to the required pharmacological properties.
• Route Analyze: We identify the most appropriate route for the production of API. Scouting during the initial process gives profitable benefits such as reducing the production of chemical waste and enhancing adaptability, decreasing the processing period, and advancing the grade and safety profiles to largely expedite the drug processing and manufacturing activities.
• Chemical Reactions: Our proficient chemists rigidly conduct reactions to transform raw materials into the required API intermediate by processing the proper development method, optimizing pressure, temperature, and solvent to attain high yields and purity. Chemical reactions often agitate complex processes, so precise control of reaction conditions and other parameters is essential.
• Purification and Isolation: After suitable compounds are formed they are purified and separated from impurities to bring off the requisite purity level. Methods like distillation, filtration, Crystallization, and chromatography are integrated to isolate the API in its purest form.
• Quality Control: We make sure that the API matches the highest standards during the whole process, constantly keeping a check on purity, strength, identity, and safety. 
• Scale-up: Scale-up is defined as the procedure of increasing batch size as the requirement for API increases. This requires improving the synthesis process, increasing the size of the apparatus used, and ensuring steady quality at higher production rates. Further careful consideration is given to the availability of raw materials, environmental effects, and regulatory adherence throughout the procedure.

Physicochemical assessment of APIs

API Processability

At Macsen Labs our chemist comprehends the physical and chemical properties of an API, by optimizing the formulation process, and enhancing production proficiency. API processability is essential in pharmaceutical development, as it directly impacts the drug’s formulation potency, stability, and pharmacokinetics.

To evaluate API processability it’s essential to check out several key factors. And we are here to help you answer these questions concerning the evaluation process:
Q. What are the solubility properties of API?
Solubility is the key factor in API processability, it regulates the API’s capacity to dissolve and get absorbed in the body. However, APIs with low solubility requires specific formulation techniques, for instance, solubility enhancers or micronization are utilized to develop dissolution rate and bioavailability.

Q. What is the particle size and distribution of the API?
Particle size and distribution can influence the API’s flow properties, dissolution rates and flexibility. Smaller and identical-sized particles are more easily integrated with excipients and show better flowability.

Q. What is the Hygroscopicity of the API?
Hygroscopicity is the chemical property of an API to absorb moisture from the environment, which can affect the stability, flexibility, and flow properties. Therefore, these APIs require specific packaging or formulation procedures to inhibit moisture absorption and sustaining product quality.

Q. What is the API’s compatibility with excipients?
For a successful formulation the compatibility of the API with diverse excipients like binders, disintegrants, and fillers are essential. Incompatibility can affect the API’s stability, dissolution, or bioavailability.

Q. What are the possible stability issues associated with API?
It is important to ensure product potency and safety. Factors like temperature, humidity, light, and pH can influence the API’s stability. Therefore it’s essential to detect potential stability threats, and device-appropriate storage conditions and formulation procedures to reduce degradation.

API Bioavailability

At Macsen Labs our chemists utilize their vast knowledge and cutting-edge expertise to generate effective pharmaceuticals. API bioavailability means the rate and extent to which API is absorbed into the body and reaches systemic circulation. It plays a crucial role in determining the drug’s efficacy and safety. Various strategies are employed to enhance API bioavailability: 

• Particle size reduction: Minimizing the particle size of an API has a profound effect on its absorption. By increasing the surface area of the API, micronization upgrades dissolution and absorption rates. Further, formulating APIs as nanoparticles can enhance their permeability, solubility, and cellular uptake, making them more effective.
• Solubility Enhancement: At times APIs have solubility issues that restrain their absorption and to reduce this there are several techniques such as converting an API into a salt form which can enhance its solubility, forming complexes between the API and suitable carriers, or Dispersing the API in a carrier matrix. These can increase their solubility, dissolution rate, and bioavailability. 
• Formulation Techniques: The way an API is formulated affects its bioavailability, for instance, amorphous forms of API exhibit higher dissolution rates and solubility in contrast to crystalline forms. Further, integrating APIs into lipid-based formulations like liposomes or micelles can advance their absorption and bioavailability. Also, sustained-formulations help maintain therapeutic drug levels for an extended span minimizing dosing frequency. 
• Co-administration with Absorption Enhancers: Chelating agents have been shown to enhance the absorption of certain APIs by minimizing their interaction with intestinal contents. They form complexes with metal ions, and inhibit the growth of insoluble compounds, which otherwise hinder API absorption. Also, adding surfactants increases the solubility and permeability of the API by reducing the surface tension of the API, and helps in penetrating easily into the intestinal epithelium enhancing API’s pharmacokinetics.
• Route of Administration: Directly injecting APIs into the bloodstream ensures complete absorption and rapid onset of action. On the other hand, sublingual or buccal administration, comprises the placing of APIs under the tongue or cheek, where they are absorbed directly into the bloodstream, also are the routes that evades the first pass metabolism into the liver, potentially advancing bioavailability. 

By carefully determining and implementing these significant strategies, we optimize the delivery of APIs by enhancing drug efficacy and reducing the required dosage.

API Stability Testing

API stability testing is the most crucial and rigorous testing designed to maintain its potency, quality, and safety which cannot be overstated. By subjecting the APIs to diverse environmental conditions such as temperature, humidity, light, and pH, our expertise identifies the potential degradation pathways and analyzes their impact on the API’s physical, chemical, and biological properties. The key objective of this stability testing is to ensure that the API retains its intended efficacy, purity, and identity throughout its shelf life.

To get a new drug approval from the government authorization, an API stability test is a compulsory requirement. By showing that the API can withstand various environmental conditions like transportation, and storage, we assure it complies with the regulatory level. The APIs are subjected to different ranges of temperature and humidity levels to analyze their long-term storage and susceptibility. And to assess their sensitivity to photodegradation they are examined under various light conditions. APIs stability is also estimated at different pH values to calculate its liability to hydrolysis and other pH-dependent degradation.

API Purity

The purity of Active Pharmaceutical Ingredients (API) is the most crucial factor in the production of pharmaceutical products, even a minute impurity can have undesirable effects, compromising its potency, stability, potential, and bioavailability, potentially reducing therapeutic effects and adverse reactions.

Various analytical techniques are employed to ensure API purity, such as:

• Chromatography: Methods like high-performance liquid chromatography (HPLC) and gas chromatography (GC) are utilized for separating and estimating impurities in API.
• Spectroscopy: The unique spectral properties of impurities are evaluated with techniques like infrared spectroscopy (IR) and ultraviolet-visible spectroscopy (UV-Vis), which detect and identify impurities accurately. 
• Mass spectrometry: It’s a powerful device that helps in identifying and quantifying impurities even at trace levels.
• Elemental analysis: To determine the elemental composition of the API, this technique is utilized to identify inorganic impurities.

Macsen’s Areas of Special Expertise

At Macsen Labs, we provide extensive customized API synthesis services that fit the unique requirements of our clients. Our expertise expands to a wide span of complex synthesis.

Reactions we have experience in handling 

We conduct diverse important reactions for API synthesis in our Labs, such as:

• Halogenation reactions like Chlorination, bromination, etc. 
• Condensation Reactions
• Reduction Reactions 
• Oxidation Reactions 
• Cyclisation Reactions
• Coupling Reactions

 Process Optimization

We emphasize enhancing processes for organic compounds to advance efficiency and sustainability, which includes:

• Cost-effective and Eco-friendly processes are both economical and environmentally friendly.
• We target higher cost-effectiveness by precisely analyzing routes for feasibility and optimization. 
• We use techniques like LCMS, HPLC, IR, NMR, and GC for impurity synthesis and Characterization.
• We ensure the non-infringement of selected routes and evaluate the compound’s purity and polymorphic forms by screening patent databases. 

Flow Chemistry

With flow chemistry, we refine the reaction parameters which significantly improve reproducibility and safety. This method is especially effective for challenging and sensitive reactions which needs more attention to detail. 

Scale-Up

We ensure an ideal transition from small lab experiments to large-scale commercial production. With our top-grade facilities and expert team, we make sure everything runs smoothly and on-time. 

Additional Services

 We provide a range of other services like:

• Process Development: We make parallel associations with our clients to generate efficient and cost-effective synthesis routes and minimize waste at every step. 
• Regulatory Compliance: Our procedures meet stringent regulatory grades like GMP and ICH guidelines.
• Quality Control: We ensure that the product is prime & Consistent by maintaining rigid quality control throughout the synthesis procedures 

Our Facilities & Equipment

At Macsen Labs we are committed to delivering top-notch Active Pharmaceutical ingredients (APIs) via our state-of-the-art facilities and advanced equipment. As a cGMP manufacturer, we rigorously follow Good Laboratory Practices (GLP) to ensure our analytical methods are accurate, precise, and reliable. 

• We initiate and validate customized scientific methods for all the APIs ensuring precise quantification and characterization.
• Our proficient chemists employ advanced techniques and cutting-edge instruments to generate sensitive and selective testing procedures.  
• Our state-of-the-art facility is equipped with a range of complex instruments like LC-MS/MS, GC-MS/MS, ICP-OES, FTIR, and HPLC. Adjunct to our in-house facilities, we have a partnership with other advanced facilities enabling us to provide additional services such as NMR, XRD, SEM and TEM.
• We assure you the highest quality and consistency of our APIs, by incorporating our analytical expertise with cutting-edge instrumentation and attaining the rigorous quality set by regulatory authorities and our clients.

Comprehensive API Development and Quality Assurance by Macsen

At Macsen, we guarantee adherence to the highest industry standards by offering a comprehensive portfolio of services for API synthesis and quality assurance. Our technical proficiency covers crucial procedures and assessments necessary for dependable API development.

Quality by Design (QbD) Approach

Macsen integrates the QbD framework into every project, emphasizing thorough process understanding and risk management. This proactive approach ensures consistent quality by identifying and controlling potential variables early in the development process, reducing the risk of deviations during manufacturing.

Process Validation

We conduct rigorous validation studies to ensure that the API manufacturing process is consistent and reproducible across batches. This step is crucial for scaling up production without compromising the quality or performance of the final product.

Impurity Profiling

We perform comprehensive impurity profiling to ensure the safety and efficacy of APIs:

Nitrosamine and NDSRI Impurity Management: Detection, control, and mitigation of nitrosamines and related impurities, which are of particular concern due to their potential carcinogenic risks.
Elemental Impurities Profiling: Evaluation of heavy metals and other elemental impurities to comply with ICH Q3D guidelines.
Impurity Characterization: Identification and quantification of all potential impurities to meet regulatory standards.

Residual Solvent Risk Assessment

Macsen ensures that residual solvents in APIs are controlled within acceptable limits as per ICH Q3C guidelines. This involves assessing risks and optimizing processes to minimize solvent residues, ensuring product safety and compliance.

Carcinogenic and Mutagenic Risk Assessment

We conduct detailed risk assessments for potential carcinogenic and mutagenic substances. These studies help identify and mitigate risks associated with raw materials, intermediates, and final APIs, ensuring compliance with regulatory requirements.

Forced Degradation Studies

Forced degradation studies help us identify potential degradation pathways under extreme conditions. This information guides formulation development, enabling the design of stable APIs with an extended shelf life.

General Stability Studies

Stability studies are essential to ensure that APIs retain their potency, purity, and safety over time. We simulate a range of environmental conditions to predict shelf life and define optimal storage conditions.

Photostability Studies

Our photostability studies evaluate the effects of light exposure on APIs, ensuring they remain stable under storage and usage conditions. This step is critical for products exposed to light during manufacturing or packaging.

Hygroscopicity Studies

Hygroscopicity studies assess how APIs interact with moisture in the environment. This helps determine the ideal packaging and storage requirements to maintain the stability and integrity of the product.

Study of Crystalline/Polymorphic Forms

Macsen conducts extensive studies on crystalline and polymorphic forms to optimize the physical and chemical properties of APIs. These studies ensure improved solubility, stability, and bioavailability, tailored to specific therapeutic applications.

Analytical Method Validation

Our team develops and validates robust analytical methods to ensure accurate, reproducible, and reliable results throughout the API lifecycle. This includes testing for potency, impurities, and other critical parameters.

Cleaning Validation

We implement cleaning validation protocols to eliminate the risk of cross-contamination between production batches. This is particularly vital in multiproduct facilities and for APIs with high potency or specific toxicity profiles.

Microbiological Purity Testing

Macsen ensures that APIs, especially those intended for sterile or injectable formulations, meet strict microbiological purity standards. This includes routine microbial testing and control measures to prevent contamination.

By leveraging these technical services, we provide clients with APIs that meet global regulatory requirements, ensuring the highest standards of quality and safety. Whether it’s advanced impurity profiling, robust stability studies, or detailed risk assessments, our comprehensive solutions make us your trusted partner in API development.

Why Choose Us?

With years of experience in industry and developing our own products, we have acquired proficiency in organic and inorganic synthesis from lab-scale projects to large-scale production.

Macsen Labs stands out amongst other API suppliers because of our unique offerings:

• We ensure you get what you need as soon as possible by streamlining our techniques to speed up the formulation of custom APIs.
• We value your time and are committed to providing timely delivery and swift response to your inquiries and requests.
• We offer competitive pricing without compromising on quality, as we focus on enhancing efficiency and upgrading procurement.
• We strictly attach to our Non-Disclosure and Confidentiality Agreements policy, so your information is safe with us.

For a detailed description about Macsen’s Custom Synthesis & Contract Research, you may refer here.

By blending our deep expertise in complex synthesis, and with a commitment to quality and customer satisfaction, Macsen Labs is here to be your trusted partner in custom API development and manufacturing!

Send us your enquiry-

(or drop us a mail at sales@macsenlab.com, marketing@macsenlab.com)

Other Resources

What is Custom Synthesis? Advantages, Challenges & Important factors