The Application Method And Precautions Of Powder Direct Compression Tablet

Due to the obvious advantages of direct powder compression, such as relatively simple process, no need for granulation and drying, fast product disintegration or dissolution, and stable product quality, about 40% of tablet varieties abroad have been produced by this process .

1 Application

① Used for drugs that are easy to change color and decompose when exposed to humidity or heat. The color turns yellow and the content decreases, especially when affected by moisture, temperature, metal ions, etc., it is more likely to cause drug deterioration; aminophylline is easy to decompose and change color when exposed to humidity and heat, and emits a strong ammonia odor; It is also unstable, the content drops, and the dissolution rate is unqualified; vitamins B1, B2, B6, etc. are unstable to humidity, heat, and metal ions. If these drugs are granulated by conventional wet methods, the product quality will be affected because the drugs are in contact with the solvent in the binder and dried at high temperature during the production process. However, using the powder direct compression process, the prepared tablet has a smooth surface, no cracks and sticky punches, the difference in tablet weight is small, and the disintegration time limit is short. After accelerated experiments and observation of reserved samples, all quality indicators of the tablet have no change.

②Used for easily hydrolyzed drugs such as esters and amides, because meclofenoxate hydrochloride is very easy to hydrolyze, the conventional wet granulation process is adopted, because the binder is added during the production process, which contains moisture, and the drug will decompose under dry high temperature conditions Acceleration, thereby affecting the quality of medicines, not only reduces the content of medicines, but also increases degradation products, reducing curative effect and increasing side effects. However, it is produced by powder direct compression technology, which avoids contact with water, and can choose excipients with low hygroscopicity to further ensure the stability of the drug during storage.

③ The dissolution rate of drugs with low solubility or hydrophobicity is greatly affected by their specific surface area and the surface properties of finished drugs. Through pharmaceutical methods, hydrophilic excipients are selected and directly compressed by powder. After the drug is disintegrated, the drug is released directly from the powder, the dispersion degree is increased, the dissolution is accelerated, and the relative bioavailability is improved.

④ The melting point of the compound drug cyclomandelate used for low melting point and eutectic is 50°C-62°C, conventional wet granulation can cause the drug to melt and affect the quality; the compound preparation of ephedrine hydrochloride and diphenhydramine hydrochloride, wet-processed When the grains are dry, the two can produce eutectic, which is not easy to dry. The powder direct compression process can effectively solve the above problems.

2 Precautions

① The properties of the drug and the excipients should be similar. When performing powder direct compression, the physical properties such as bulk density, particle size and particle size distribution of the drug and the excipients should be similar to facilitate uniform mixing, especially for drugs with small specifications that need to be measured for content uniformity. , various accessories must be carefully selected.

②The insoluble lubricant must be added last. The insoluble lubricant used for powder direct compression must be added last, that is, the raw material and other excipients are mixed evenly before adding the insoluble lubricant, and the mixing time must be well controlled, otherwise it will seriously affect the Disintegration or dissolution. In addition, when pregelatinized starch, microcrystalline cellulose, etc. are used as auxiliary materials, if the dosage of magnesium stearate is large and the mixing time is long, the tablet will soften, so the general dosage should be less than 0.75%, and the dosage should be adjusted accordingly. Mixing time, rotational speed and intensity were verified.

③Content measurement after mixing is the same as the production process of conventional wet granulation. The content of each raw and auxiliary material for direct powder compression should be measured after mixing to ensure that the quality of intermediate products and finished products meets the specified standards.

④After the small test, sufficient test scale-up must be carried out. Under normal circumstances, unqualified tablets compressed by the powder direct compression process should not be reworked. Because the tablet must be crushed again for rework, the compressibility of the crushed material will be significantly reduced, so that it is not suitable for direct compression. Therefore, from a small test to a large-scale production, a pilot test must be carried out and fully verified, and the pilot test should use the same type of equipment as the subsequent large-scale production, so that the determined parameters can guide large-scale production.

⑤ Use of microcrystalline cellulose When the tablet hardness and friability are unqualified, microcrystalline cellulose can be added, and the dosage can be as high as 65%; it can also be pressed into large tablets, then broken into granules, and then compressed into tablets. method, satisfactory results can be obtained.

⑥Promptly deal with abnormalities during tablet compression During the tablet compression process, samples should be taken in time according to the standard operating procedures to observe the appearance of the tablet and measure the quality indicators such as tablet weight difference, hardness, friability, disintegration time, and tablet thickness. And observe the operation of the equipment, report the abnormal situation in time and take emergency measures, record the abnormal phenomenon and processing results in detail, and conduct detailed analysis to ensure product quality.

With the introduction of new foreign pharmaceutical excipients, the continuous development and listing of new varieties of domestic pharmaceutical excipients, and the continuous updating, improvement, and perfection of tableting equipment, the application of powder direct compression method in China will gradually increase.