What is Solid oral tablets direct compression I
Writer： admin Time：2020-04-14 18:03 Browse：℃
1.Foreword
Direct compress (DC) of powder is a technology came up by Milosovitch in 1962. before then, raw materials should be granulated before being compressed. Since moist heating unit is not needed during DC, some API sensitive to moisture and heat can be used in oral solid tablets. The appearance of DC promotes development of oral solid tablets. Currently, DC has been applied widely in primary clinical preparation development of new medicine. Since new medicine is not that easy to be developed, DC, a preparation technology of short period, can speed up primary clinical experiment. Meanwhile, it can avoid high cost due to high failure rate of new medicine development. DC will be introduced below.
2.Panorama of DC
Comparison between traditional oral solid tablet technology with DC can give us a complete and accurate panorama of DC.
1)Advantages of direct compression
Because of convenience of prescription process, DC has become preferred among oral solid tablet technologies. Mixing API, thinner, adhesive, disintegrant and lubricant simply and tableting then, this is the mode of DC. Compared with wet granulation, moisture and heat can be avoided and therefore, API sensitive to moisture and heat can be exploited. Besides, products produced by DC will not have problems of aging and slow dissolution which are always caused by traditional technologies.
DC unit is of less and simpler operation steps, including mixing and compressing only. However, wet granulation or dry granulation has more operation steps and verification, yield, cleaning and record should be done in every step. In practical production, GMP of them can lead to high cost in production equipment and labors.
|
Property |
Granulation (wet & dry) |
DC |
|
Compressibility |
Tablets good hardness can be made from raw auxiliary materials of bad compressibility (wet granulation) |
API of high loading efficiency and bad compressibility might have problem in prescription compress |
|
Fluidity |
Material of good fluidity can be made through granulation (wet and dry granulation) |
Flow aid is usually added |
|
Particle size |
Large size and wide distribution (wet and dry granulation) |
Small size and narrow distribution |
|
Content uniformity |
API can be bound to auxiliary material steadily to achieve high content uniformity through granulation |
Stratification might occur between different raw auxiliary materials during transferring and tablet pressing |
|
Lubricity |
Not sensitive to lubricity (wet granulation) |
Mixing time and frequency are possibly short when accepted |
|
Disintegrating |
Wet granulation will weaken function of internal disintegrant (smallest influence on CCNa) |
Disintegrant of small volume |
|
Dissolution |
API can obtain better hydrophilic property after wet granulation. But its dissolution lowers down, especially when there is no internal disintegrant (wet & dry granulation). |
Surfactant might be needed |
|
Cost |
High cost on equipment, time, energy and labor |
High cost on auxiliary materials |
|
Sensitivity to API |
Small |
Large |
|
API stability |
API sensitive to moisture and heat is not proper |
None |
|
Compressing rotating speed |
High |
Low speed is suggested when material has bad fluidity |
2)Disadvantages
Different from wet granulation, DC will be influenced by physical and chemical properties of auxiliary materials, such as high loading efficiency, fluidity and compressibility, especially during magnification. Therefore, product property is an important benchmark for the use of DC.
One of the disadvantages of DC is its magnification, which is mainly about compressibility and fluidity caused by rotating speed change during industrial tablet press. Through the second granulation, wet & dry granulation can improve compressibility and fluidity of materials. Therefore, they acquires better magnification than DC. Material fluidity in DC mainly depend on the fluidity and compressibility of raw auxiliary material. Normally, APU, especially prescription of powdering or high loading efficiency is of bad fluidity and compressibility. Auxiliary materials itself of DC also are also some insufficient. For example, MCC which provides high dilutability, adhesion and compressibility is of bad fluidity and is sensitive to compressing speed.
Another advantage of DC is content uniformity. Different from wet/dry granulation, SC can only mix API with auxiliary materials primarily. They are bond to each other through Coulomb force and surface tension. But such a force is not strong so that different materials might stratify during mixing or pressing, leading to bad content uniformity. How to solve this problem? One method is to narrow the size and density distribution of API and auxiliary materials. However, sometime API is powdered, so it seems unpractical to unify size of all materials. For this problem, orderly mixing can function. In practical operation, API of small size can be premixed with large auxiliary material particles of certain adhesion (usually MCC), and then mixed with other auxiliary materials. Such as method can not only solve the above problem effectively, but also assist development of tablets with LE of 0.1%.
Similar to dry granulation, DC cannot produce colored tablets directly. High shear wet granulation can produce tablets of single color, while DC cannot mix colorant effectively and uniformly to cause color difference. Also, colorant will pollute machine and color sufferers’ skin.
