The solvent replacement process are optimized by the refractive index trend data
This article is about the in situ refractometer how to optimize the API API process online articles are the first of a series of three articles).
The manufacture of medicinal active ingredients (API) is a key part of the pharmaceutical production.API API process usually begin from starting material into reactor, chemical bond fracture and form a new button in the reactor.After the reaction, through centrifuge and filter downstream purification steps such as the separation of active ingredients.In general, API API in the form of solid from liquid phase recovery, the solvent used in the special solvent recovery unit.Solvent recovery is vital for the pharmaceutical industry, which will help you to reduce costs and reduce the impact on the environment.Solid API API end products, after drying can be used as intermediates or used for dispensing drugs in the end.
Development and optimization of pharmaceutical process is a complicated and lengthy process, take years to complete.In order to simplify the process and speed up the drugs listed pharmaceutical companies must focus on is to scale up and can be in the commercial production scale replica of the efficient process.Process of equivalent is to improve a method of process step by step amplification.
Equivalence refers to the process used to produce the same product of different machining process consistency and comparability.For example, the us food and drug administration (FDA) require each company validation process, used to prove the consistency of the pharmaceutical technology.From development to the whole expansion process need to perform process validation, to ensure consistent quality control and production.FDA process validation process equivalence is guide a key element.
The refractive index as process analysis technique (PAT) tools
It has been proved that the refractive index (RI) is a kind of practical tool for process analysis technology (PAT), can be used in the development of the API API manufacturing process, design and optimization.Refractive index of the continuous online measurement can provide data parameters of the process, help to understand and design the different process steps.Through these data for detecting deviation and to ensure that the process to create the equivalent process curve.Visa refractometerCan provide trend data, and has the required reliability and repeatability of the pharmaceutical industry.Refractive index measurement from the bubbles, the influence of the solid particles or liquid color.Refractive index of these features make it a API API production process in the choice of many application scenarios.
Refractive index is the basic physical properties of liquid, is generally not affected by liquid volume.This can be simplified from the lab to pilot to commercial production expansion process.
Trend is the real-time data, and can with refractive index curve comparison test in the process to determine process equivalence, and help to assess and determine other key process parameters, the deviation and the ideal operating conditions.In addition, based on the technological process of the refractive index data curve helps to identify the problems during the scale and continuously optimize existing process.
Optimization of the solvent replacement
Solvent replacement API API is common purification steps in the process of production, the purpose is to use more suitable for the next processing step of solvent displacement reaction of the original solvent.Solvent replacement is usually completed by distillation.In the process of distillation, the refractive index measurement used to monitor the top (condenser) and liquid concentration at the bottom of the products, for example, to ensure that you get the correct API API or solvent concentration, determine the time point of adding solvent, solvent and reducing overall consumption.During the period of development, the refractive index can also be used to obtain important technology research and development data, such as vapor liquid equilibrium (VLE) data.
Online measure would also help to identify the problems existing in the process.For example, in the case of a customer, visa hold refractometer trend data during the process scale to ensure that two plants (one in the United States, in Europe) and laboratory process equivalence between process curve.Online data based on refractometer, the customer found the factory did not press design, need to perform additional displacement steps to reach and r&d laboratory and pilot plant process design in Europe the same purity.In this case, the refractive index trend data is a troubleshooting tool, and allows customers to maintain the good operation of the factory.
By refractive index measurement, our customer found that the deviation between laboratory and pilot plant.Then, they will be able to immediately take measures to reduce solvent consumption and improve product yield.Refractive index is used to measure the customer in the lab early stage to study the mixture, obtain the VLE data and process data curve, solvent displacement process and design.Online refractive index measurement simplified from the lab to pilot the scale-up process.
Refractive index measurement is the ideal PAT tool for solvent displacement design, monitoring and optimization of the process, and process data and troubleshooting for important trend analysis tools.
