abstract
Membrane-controlled sustained-release preparation is a very common slow-release model, and the coating process is the most important part in the preparation process. This paper will discuss the research and control of the slow-release coating process in detail.
Packaging process is a common process in ordinary solid oral preparations. Different components of coating prescriptions can be selected according to the different purposes of the coating, and the depth of research and the indexes of the coating process are also different.
In terms of ordinary rapid release preparations, the coating function is generally protective and recognizable, the main content of the coating process and appropriate weight gain, and AQL inspection is mainly used as the key control item in the production process. However, the function of the coating process is not only protective, recognizable and controlling the drug release. In order to realize the selection of the target film material, the quality of the film.
Selection of membrane material prescription is a more complex topic, for the development of the researchers on the premise of clear goals of different film characteristics and function have considerable understanding, in all the development of membrane controlled slow-release formulation core is to design appropriate release mechanism according to the target release behavior is to choose the appropriate material ratio and optimize the corresponding coating process, material ratio research and coating process research in the preparation of different slow-release mechanism is basically similar.
The composition of slow release film material is mainly reflected in the ratio of different functional components to coating weight control, usually based on past experience of key material DOE screening, because the slow release film material prescription screening is based on release mechanism so is not discussed in this paper, the following mainly from the perspective of slow-release coating process of noteworthy.
1. Explore the parameters of the slow-release coating layer
Study of the formulation of the coating fluid
The main objective of coating liquid preparation is to obtain a stable coating liquid system, which mainly consists of material and solvent. Stable coating system refers to that the coating liquid is always in a uniform state during the whole process of coating and applying medicine. This uniform state is reflected in the physical and chemical stability, that is, the viscosity of the coating liquid and the consistency of the material after film formation in different coating time periods. The study of coating liquid will determine how long the prepared coating liquid can be stored, and then it can give appropriate suggestions on the choice of flow rate during the coating process. For example, the influence of the configuration of the coating solvent system.
The screening of coating material composition is the main content of the development of coating prescription. In the process of this study, we need to select the dissolution characteristics and process feasibility of the solvent ratio, solution concentration and dissolution sequence. In this study, it is necessary to quantify the dissolution capacity of various materials in related solvents to provide data support for the formulation of later process parameters. The conventional method is to directly use CQA as the evaluation index to confirm the rationality of relevant parameters (this method evaluates the trial and error strategy of the process, with the most direct conclusion, but the weak interpretation of specific influencing factors has limited deep understanding of the process) or continuous viscosity determination, IR, Tg, DSC, XRPD to confirm the adequacy of dissolution and the stability of the solution to obtain more process understanding.
Study on chip-core coating parameters
The chip coating parameters involve the equipment input parameters (temperature, pressure, dew point, air volume, flow rate, coating pot speed) and material output parameters (instantaneous temperature of chip bed, chip bed temperature, efficiency, etc.).
The core content of the research process is to confirm the influence of the material output parameters of the system through the correlation between the material output parameters in the coating pot and the verification of the product CQA. For example, the product film temperature and drying efficiency will affect the final product dissolution behavior and AQL, so can affect the input parameters is the focus of the coating parameters, such as temperature, dew point, air volume and coating flow rate will affect the transfer of energy to affect the film temperature of bed material, atomization pressure will affect the size of the droplets and have a certain impact on the drying efficiency.
The influence of the above input parameters on product quality is staggered and complex. In the actual research and development process, the output material attribute needs to be studied as the key index in order to obtain the target material attribute parameters. The following figure shows the research results of the control area of the input parameters such as inlet temperature, humidity and coating flow rate by taking the bed output temperature and coating efficiency as the key indicators.
Determination of steady state coating parameters: after obtaining the target material attribute parameters need supplementary research to optimize the coating parameters can be stable output target material attribute input parameters make the controllability of the whole coating process, film quality more stable and reduce the difference between batch and batch, can also be understood as the coating piece target attribute parameters and the input energy balance point confirmation.
Study on chip core aging parameters
For the aging process study, we can refer to the "aging process of slow-release coating". How to determine whether the aging step is required for a coating preparation: ① Carry out the high temperature challenge experiment and high humidity challenge experiment of the coating preparation. ② If the release of the preparation does not increase in the above challenge test will not decrease, the aging step is not required. Simple summary is, organic solvent coating system aging process in less impact on product quality can describe the process as drying process, water bulk coating system aging process need careful study, notice, water bulk coating is not a simple deposition process, is a accompanied by water evaporation makes the polymer constantly concentrated on the base surface tightly arranged, with further evaporation particles under the action of capillary deformation and crosslinking formation target membrane.
2. Analysis of the problems related to slow-release coating
Clothing uniformity problem
This is less attention in fast release preparations, but coating uniformity is also a key issue for slow release. It mainly involves two aspects of uniformity, one: the coating uniformity of the single unit itself, and the other: the uniformity between the preparation units. Preparation of itself uneven or uneven between units will release behavior, lead to release and RSD unqualified, in view of this problem we need to determine whether the uniformity does occur, conditional laboratory can use XuCT technology or SR- μ CT technology for intuitive judgment, can also use the tablet weight difference method or product drug method for content uniformity detection coating uniformity. The above problems occur mainly from the design of the coating pot guide rail, the coating parameters and the structure design of the preparation core. There are similar problems in the practice process that can refer to the above factors.
Process amplification problem
The question of process amplification can be found in many books and literature, There are many transformations of various formulas, The author believes that in the research stage, the confirmation of the material in the whole process of the own status parameters (not the equipment parameters) and the related equipment parameters information is the core, In practice, the consistency of the material state parameters through the adjustment of equipment parameters (the amplification process should ensure the consistency of the process attributes of the material (the core of the coating pot) in each order of magnitude, Material properties are mainly two sheet bed temperatures, Therefore, it is necessary to control the dew point, negative pressure and atomization pressure with the flow rate, temperature and air volume (for the same aperture nozzle, it is necessary to maintain the consistency of atomization pressure within a certain range of flow rate, For the spray guns with different apertures, the amplification process needs to make the atomization pressure adjusted according to the amplification characteristics of the flow rate to ensure the consistency of the droplet size)).
3. Talk about the control strategy of slow-release coating
Slow-release coating is different from fast-release coating. The control strategy of slow-release coating process is a comprehensive control scheme based on the research of first-class parameters, and the degree of control reflects the degree of product quality understanding and research.
In the actual research process, the author found that the study of slow-release preparation coating is a process of continuous climbing. In the limited experimental environment, only through continuous exploration can we more deeply understand the significance of product quality given by each material and each parameter. The views in the paper only represent the author's practical experience of the author, or cannot be applied to all the process of slow release coating. In the paper, we hope that readers can communicate and cooperate to explore the development strategy of such products.
