跳至主要内容

Analysis of the Process and Problems of API Process Amplification

 The process amplification of API refers to the enlargement of the production of API from laboratory scale to industrial scale, which is the only way from research and development to production of pharmaceutical preparations. Process scale-up is an indispensable development process for APIs to adopt large-scale production and realize industrialization. Its purpose is to verify, review, and improve the reaction conditions determined by the laboratory process, and to study the structure, material, and material of the selected industrial production equipment. Installation and workshop layout, etc., can provide data, materials and consumption for formal production, and are effective measures to reduce industrialization risks. Today, let’s take a brief look at the process of API process amplification and the problems that may arise in the process of API process amplification.

process amplification of API

The process of bulk drug process amplification

Step1:

In pharmaceutical product development, the API development stage is an early stage in the life cycle of the drug product. The ultimate goal of this stage is to design a process suitable for commercial production that can consistently produce a product that meets its key quality attributes.An intermediate is a material produced in the process of an API that must undergo further molecular changes or refinements before it can become an API. Drug production depends on the customized synthesis of pharmaceutical intermediates. After an hour of research on the synthesis of the API, the control parameters for the chemical reactions are obtained to achieve the purpose of manufacturing in compliance with the quality standard API. In the scaling-up stage of API process, material balance and time balance should be done step by step according to the production process of small test, and documents should be sorted out.The purpose of material balance is to select the appropriate size of equipment, the purpose of time balance is to obtain the production time of a single batch, and ultimately derive the total batch or the planned time to complete a task.

Step2:

To choose the most suitable equipment, you can ignore the existing equipment and just draw a simple flow chart. Every equipment should be reflected on the map, every logistics should be reflected on the map, and related controls will not be considered for the time being.

Step3:

Consider the stirring blade of the reactor, consider the public engineering system, such as the heat exchange medium of the reactor, the cooling of the condenser, the public engineering required by the medium, the vacuum source, and the compressed air; consider the key control instruments or central control measures, such as Online PH, online sampling, temperature and pressure control, etc. To perfect the drawings on the basis of Step 2, documents must be obtained for each process, not ideas in the brain.

Step4:

Make recommendations for equipment rectification in comparison with existing equipment.

Step5:

Get process flow chart, equipment plan and equipment list. Draw a complete process flow chart with control points on the basis of the first four steps. Draw the equipment plan and compile a complete equipment list.

Amplification of the API process, that is, the production of APIs from laboratory scale to industrial scale, is an indispensable development process for APIs to adopt large-scale production and realize industrialization. Medicilon is committed to providing customers with fast and efficient services. Its unique “customized” pharmaceutical process research and development model also fully embodies this concept, enabling customers to obtain APIs as soon as possible for clinical research. Medicilon’s process research and development department has rich experience in process optimization and the development of new, safe and environmentally friendly process routes, and is committed to helping customers develop stable and low-cost processes suitable for mass production.

Problems of API Process

Problems that may occur in the process of API process amplification

(1) Change of reaction selectivity

The most common problem in process scale-up is the change of reaction selectivity, which will affect the yield and purity of the product. This is mainly due to the inconsistency of the mixing effect and production in the small-scale trial. If the influence of the speed has been evaluated in the small test, when a problem occurs, the cause will be quickly found. The reactors in the pilot plant are equipped with frequency conversion speed control, and appropriate adjustments can be made to determine the appropriate speed.

(2) New crystal forms appear in process amplification

During the scale-up, the separation of the product will also cause problems, the washing effect of the filter cake in the production does not reach the level of the small test, and the impurities cannot be completely washed away. The three-in-one filter, washing and drying equipment with stirring can replace the centrifuge under certain process conditions. The three-in-one equipment can be directly added to the solvent for washing and beating after filtering. The washing effect is better than that of the centrifuge.

(3) The impact of production operation time

It is necessary to carry out experiments on the impact of extended time on products for small trials. In actual production, due to the extension of the distillation time, the product decomposes and side reactions occur many times.

The preparation of API is very important in pharmaceutical preparation research and development. It can provide qualified API for pharmacological and toxicological research, preparation and clinical research in the process of drug development, and provide detailed information for drug quality research. Therefore, it is important to provide the preparation technology of API in line with industrial production.

Related Articles:

Confirm the Structure of Drug to Find Whether the Structure of the Synthetic API is Correct

How to Screen the Cost-effective Route of API and Intermediates

API process development of the new drug IND stage

Several Major Issues that Need to be Paid Attention to API Process Scale-up

标签：

评论

发表评论

此博客中的热门博文

What is preclinical testing?

In the process of  preclinical testing  of a compound or biological agent into a drug, the compound involved must go through the testing phase. First, we need to identify potential targets that can treat the disease. Then, a variety of compounds or preparations are screened out. Any compound that has shown potential as a drug for the treatment of this disease needs to be tested for toxicity before clinical testing to reduce the possibility of injury. preclinical testing What is the basis of preclinical testing? According to US Food and Drug Administration (FDA) regulations, a series of tests are required before a new drug is approved for use. In the first stage, basic research determines a hypothetical target for the treatment of a certain disease, and then screens small molecules or biological compounds to discover any substance with the potential to treat the disease. Then, a  preclinical research  phase followed, before which, as described above, the potential toxicity of the compou
发表评论
阅读全文

Inventory of the three major in vitro pharmacokinetic research methods

  The metabolic properties of a compound are an essential factor in whether or not it can be used as a drug in the clinical setting, so pharmacokinetic studies of newly synthesized compounds are required in drug development. In vitro incubation with liver microsomes, recombinant CYP450 enzyme lines, and in vitro incubation with hepatocytes are some of the more common in vitro drug metabolism methods. 1. In vitro incubation method with liver microsomes The metabolic stability and metabolic phenotypes of candidate compounds in different species of liver microsomes are good predictors of the metabolic properties of compounds in vivo. They are practical tools for evaluating candidate compounds in the pre-development phase of drug development. Liver microsomes include rat liver microsomes, human liver microsomes, canine liver microsomes, monkey liver microsomes, and mouse liver microsomes. In in vitro incubation of the liver, microsomes are the "gold standard" for in vitro d
发表评论
阅读全文

Novel Parkinson’s Therapies Possible with New Mouse Model

Parkinson's disease (PD) is a neurodegenerative disorder that is marked by the accumulation of the protein, α-synuclein (αS), into clumps known as Lewy bodies, which diminish neural health. Now, researchers from Brigham and Women's Hospital (BWH) report the development of a mouse model to induce PD-like αS aggregation, leading to resting tremor and abnormal movement control. The mouse responds to L-DOPA, similarly to patients with PD. The team's study (“Abrogating Native α-Synuclein Tetramers in Mice Causes a L-DOPA-Responsive Motor Syndrome Closely Resembling Parkinson’s Disease”) on the use of this transgenic mouse model appears in  Neuron . “α-Synuclein (αS) regulates vesicle exocytosis but forms insoluble deposits in PD. Developing disease-modifying therapies requires animal models that reproduce cardinal features of PD. We recently described a previously unrecognized physiological form of αS, α-helical tetramers, and showed that familial PD-causing missense mutati
发表评论
阅读全文