Would You Choose Powder Direct Compression?

In the earlier period, the selection of the process may be due to the poor fluidity and compressibility of fillers (the old three: starch, sucrose, dextrin) and other auxiliary materials, it is difficult to mix the mixed materials evenly, and the poor properties of the auxiliary materials are difficult to meet the requirements of powder direct compression. Process requirements. In terms of preparation process selection during the R&D process of solid preparations, most domestic R&D personnel still prefer wet granulation. In recent years, high-quality foreign excipient companies have brought their own products into major pharmaceutical R&D companies, such as Meggle's lactose series and Asahi Kasei's microcrystalline cellulose series. However, according to relevant reports and work contacts, we still regard powder direct pressure as the last consideration.

According to the production process classification system MCS, wet granulation is more complicated than powder direct compression and dry granulation, but it has a greater tolerance for the properties of raw materials. By adding binders to make soft materials, drying, granulation and other operations, The powder properties of the API are basically changed, and the properties of the final formulation product are more dependent on the properties of the dry particles obtained after wet granulation. When we directly choose wet granulation, the powder properties of API that affect tablet quality become insignificant. Without thinking or inclination towards craft selection is subjective and unscientific. For the sake of the so-called insurance (the impact of the API powder properties on the properties of the preparation product is minimized) and the relatively mature use of the process, it is often neglected to learn and try to use a very mature process in the world, which wastes a lot of time. Human and material resources also bring adverse hidden dangers to product stability and safety.

From the perspective of operation, the powder direct compression process only needs to select excipients with better fluidity and compressibility to mix with API, and then add the rest of the required excipients. Even if the mixed materials are prepared, it saves procedures, labor and time, and is also positive. It shows that the most obvious quality of powder direct compression lies in its economical efficiency; compared with wet granulation, the powder direct compression process avoids the contact of API with heat and humidity, and improves the stability of the drug;

The powder direct compression process can improve the disintegration and dissolution of the tablet to a certain extent, especially for insoluble drugs, the drug can only be effective if it dissolves quickly and increases the exposure in the body. From the avenue to the simplicity. Tedious steps often introduce unnecessary troubles, such as stability. However, it cannot be simple for the sake of simplicity. We need to analyze the prescription and process from a scientific point of view, and choose the appropriate process from the perspective of economy and operability.

Example: Olanzapine is an atypical antipsychotic drug developed by Eli Lilly and Company of the United States, which belongs to the BCS class II drug of the biopharmaceutical classification system. Its solubility is small, and its proportion in the preparation is low. The original research tablet adopts wet granulation process. The specifications of olanzapine are small, and the mixing uniformity of its formulation is the first obstacle in the development process. For drugs with smaller specifications, if the mixing uniformity meets the quality requirements, usually the API needs to be micronized. However, the micronized API has a smaller particle size and higher activity, tends to be in a stable state, and aggregates will occur, which will cause problems in the mixing uniformity and dissolution of the preparation. In the past, the wet granulation process was often used for preparations with small specifications. However, with the development of the excipient industry, for the preparation development

Many excipients with good powder properties have emerged as the times require, such as spray-dried lactose, which is loose and porous, and mixed with API with a smaller particle size. API can reside in the pores of lactose, avoiding the aggregation of API and improving Its mixing uniformity, and the new lactose has good fluidity and compressibility, meeting the requirements of the powder direct compression process.

The above example also gives us enlightenment. In the development of generic drugs, on the basis of fully evaluating the powder properties of the API, can we consider using the powder direct compression process to replace the forced use of excipients due to poor properties in the past? The process of wet granulation.

So, what kind of API powder properties determine the use of powder direct compression process? The MCS classification system summarizes the properties that powder direct compaction materials should have under ideal conditions. Do you want to hear it?