Solid oral tablets: direct compression III
Writer： admin Time：2020-03-18 17:12 Browse：℃
2)Disintegrant
Three super disintegrants in DC are CCS, PVPP and SSG. Compared with wet granulation, small dosage of disintegrant (0.5-4%) in DC can function quick disintegration.
For MCC which acquire some integrating property, its integrating capacity depends on compressing force and is not so strong. Super disintegrant can complement each other with MCC to quicken disintegration of tablets. When insoluble DCP is used as thinner (especially when used in huge amount), super disintegrant should be added for quick release. While when lactose monohydrate, a soluble material, is thinner, the dosage of disintegrant should be more than 2%. Otherwise, dissolution rate of product depends on slow solution of lactose instead of disintegration of tablets. Usually, integration is quicker than solution.
Mixing uniformity is vital to make the diameter of API after disintegration the primary diameter of particles. For materials of high LE, since API takes a large proportion, API particles might be compressed directly without disintegrant during mixing and tablet pressing and product solution slow down or difference expands. However, only 0.5% CCS can solve the above problem.
3)Glidant and lubricant
Fluidity of DC auxiliary materials is worse than that of material after wet granulation. To solve problem of mixing uniformity and tablet weight difference, 0.1-0.5% colloidal silicon dioxide can be added to improve fluidity.
Lubricant (usually magnesium stearate) can be added to reduce adhesion and abrasion between products and equipment molds. But some brittle material (such as MCC) doesn’t generate new surface during compression, so lubricant will form hydrophobic lubricating film on it to affect material adhesion, tablet hardness and medicine solution. Therefore, principle of lubricant is proposed: In case of normal tablet pressing, lubricant should be used as little as possible (0.5-2%), mixed at the last and individually and in a short time (2-5min).
In addition, problem of undue lubrication can be solved by a larger amount of replacing lubricant, such as stearic acid, hydrogenated vegetable oil, sodium stearyl fumarate.
4)Common DC materials and techniques
Common materials
|
Auxiliary material |
Function |
Proportion |
|
API |
Active material |
0.1-99% |
|
MCC: lactose |
Filler-adhesion |
1:1-1:5 (more common: 1:2-1:3) |
|
CCS, SSG, PVPP |
Disintegrant |
0.5-4% (more common: 2-3%) |
|
Colloidal silicon dioxide |
Glidant |
0.1-0.5% |
|
Magnesium stearate, sodium stearyl fumarate |
Lubricant |
0.5-2% |
Common techniques
A.Size of auxiliary material is about 30-50 meshes (600-300μm) and usually 40 meshes (425μm). Among them, colloidal silicon dioxide can also be 20 meshes (850μm),
B.Part of MCC can be premixed with API for 3-5min to improve API content uniformity.
C.Other auxiliary materials beside lubricant are added to continue mixing for about 10-20 min.
D.Lubricant is added and mixed for about 3-5min to avoid excessive lubrication.
E.Tablet pressing.
4.Key feature of DC
1)Compressibility
Small compressing force is required to guarantee hardness, brittleness, disintegration and solution. If LE is low, it is not difficult to achieve the above goals but mixing and content uniformity becomes a focus. However, for materials of high LE, property of API is the leading factor. For products of high amount of compressible API, the challenge is how to add litter thinner to improve its compressibility and produce products of proper hardness and brittleness. The only functional adhesion in DC is MCC, 3-5% of which can prominently improve compressibility, while DC and lactose cannot function so. Dosage of MCC is not limited, unless API can be absorbed on MCC. But such a risk can be solved by adding some soluble thinner (lactose) and super disintegrant.
2)Fluidity
Fluidity is another factor influencing weight difference and mixing uniformity. One goal of wet/dry granulation is to better material fluidity. But no granulation unit exists in DC, so auxiliary material of good fluidity is used to improve material fluidity. Materials of high LE can better their fluidity by adding some directly compressed material. But if materials is of high LE, additional glidant (such as colloidal silicon dioxide, 0.1-0.5%) is needed to better material fluidity. Gliant can also function to avoid excessive lubrication and adhesion to press punching. However, no fluidit, no separation. Large dosage of glidant will lead to stratification and material non-uniformity.
Nowadays, mandatory material feeder is applied in tablet press, since it can overcome problems caused by material fluidity and keep tablet weight uniform. But just as saying goes: “Every coin has two sides”, rotary impeller of mandatory feeder extend mixing of lubricant in another way, which will also cause excessive lubrication.
3)Content uniformity
Without granulation, DC obtains another challenge, i.e. content uniformity. DC mixes auxiliary materials simply for content uniformity. However, auxiliary materials of different density, size and shape are easy to be mixed insufficiently or excessively and problem of uniformity occurs, especially when materials contains powdered API or low LE. In practical production, orderly mixing can be applied. In this process, irregular filler (MCC usually) of big particles is premixed with API and then with other auxiliary materials. Absorption and dilution of MCC to API can solve the above problem.
5.Outlook
DC, come up in 1960s and developed for half centuries, is now applied in half table pressing. Some advantages of DC include easy technique, convenient operation, short technique developing period, less medium control unit and prevention from possible cross contamination. Of course, DC still has shortages, such as problems in content uniformity and technique magnification. The main force to push DC development is new findings in auxiliary materials which can be compressed directly. As more and more auxiliary material come to the world, DC can get further development in the future.
