Application method and precautions of powder direct pressing

1.Application

Many drugs are unstable to humidity and heat, such as cefixime is prone to discoloration when it is wet and heat, and the titer is reduced; Vitamin C is reductive and easy to be oxidized by air, resulting in yellow color and decreased content, 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 wet and hot, and gives off strong ammonia odor. Rifampicin is not stable to humidity and heat, the content is decreased, and the dissolution is not qualified. Vitamins B1, B2, B6, etc. are unstable to humidity, heat, and metal ions. If these drugs use conventional wet granulation, because in the production process, the drug and the solvent in the adhesive contact, and high temperature drying, will have an impact on the quality of the product. The tablets produced by direct powder pressing were one-sided and smooth, with little difference in weight and short disintegration time. The quality indexes of the tablets did not change after accelerated experiment and sample retention observation.

② For esters, amides and other easily hydrolyzed drugs because meclofenate hydrochloride is easy to hydrolyze, the use of conventional wet pellet process, due to the addition of adhesives in the production process, containing water, under dry high temperature conditions, drug decomposition is accelerated, thus affecting the quality of drugs, not only reducing the content of drugs, but also increasing the degradation products, so that the efficacy is reduced, side effects are increased. The use of powder direct tablet production process, to avoid contact with water, at the same time can choose small moisture primer accessories, to further ensure the stability of the drug during storage.

③ For drugs with small solubility or hydrophobicity, the dissolution of drugs with small solubility is greatly affected by their specific surface area and the surface properties of the finished drug. Through the pharmaceutical method, hydrophilic excipients are selected, and after the powder is directly pressed, the drug is directly released from the powder after disintegrating, and the dispersion is increased, the dissolution is accelerated, and the relative bioavailability is improved.

(4) The melting point of cyclomandelate, a compound drug used for low melting point and eutectic production, is 50℃ ~ 62℃, and the conventional wet granulate can cause the drug to melt and affect the quality; The compound preparation of ephedrine hydrochloride and diphenhydramine hydrochloride can produce eutectic when the grain is dried by wet method, and it is not easy to dry. The use of powder direct tablet technology can effectively solve the above problems.

2.Matters needing attention

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

② Insoluble lubricant must be added last for powder direct tablet insoluble lubricant must be added last, that is, after the raw material and other auxiliary materials are mixed evenly, and then add insoluble lubricant, and to control the mixing time, otherwise it will seriously affect the disintegration or dissolution. In addition, when pre-gumming starch and microcrystalline cellulose are used as excipients, if the amount of magnesium stearate is more and the mixing time is longer, the tablet has softening phenomenon, so the general amount should be below 0.75%, and the mixing time, speed and strength should be verified.

The same as the production process of conventional wet granulation, the content of the raw materials for direct powder pressing should be determined after mixing to ensure that the quality of intermediate products and finished products meet the specified standards.

Under normal circumstances, unqualified tablets pressed by the powder direct tablet process should not be reworked. Because the tablet must be re-crushed to rework, the compressibility of the material after crushing will be significantly reduced, so that it is not suitable for direct pressing. Therefore, from small trial to large production, pilot test must be conducted and fully verified, and the pilot test should use the same type of equipment as later large-scale production, so that the determined parameters have a guiding effect on large-scale production.

⑤ When the hardness and brittleness of microcrystalline cellulose tablets are not qualified, microcrystalline cellulose can be added, and the amount can be as high as 65%; It can also be used to press into large pieces, then broken into particles, and then press the method, can get satisfactory results.

In the process of tablet pressing, samples should be taken in time according to standard operating procedures, the appearance of tablets should be observed, the quality indicators such as tablet weight difference, hardness, fragility, disintegration time, and thickness of tablets should be measured, and the operation of the equipment should be observed, abnormal situations should be reported in time and emergency measures should be taken, abnormal phenomena and processing results should be recorded in detail, and detailed analysis should be carried out. To ensure product quality.

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