Contents of this article:
1. Introduction
2. Results and calculation
3. Discussion
4. Conclusion
1.Introduction
In this part of my report, I am going to discuss on what is meant by granulation, the importance of granulation, as well as the methods used in granulation.
So what is meant by granulation? Granulation is defined as a process where by small particle gathered into large permanent masses in which the original particle can still be identified. Besides that granulation can also be defined as a process in which fine, well mixed powder particles are adhered together and form a larger, multiparticle entities. The granules produced should be non-friable and have a suitable mechanical strength, this is to prevent the segregation of powders during compression and tableting processes. Pharmaceutical granules have a size range between 0.2-4.0 mm depending upon the subsequent use of them.
Some people may wonder that why is granulation so important in drug manufacturing processes? The reasons are because granulation increases the average particle size of our drugs. This allow the storage of raw material to become easier (since there are less dusty now). Besides that, by increasing the average particles size, the flowability of our drugs and excipients can be increased during the process of manufacturing. Optimum flowability is required for the better filling of capsule and tableting. This is because with the good flowabilty, the mass variation of our final product can be reduced, and also the differences of mass between different batches of drugs produced can be minimized. In addition to that granulation also increases the quality of our drugs especially those made into tablet form, this is because granules of optimum size allow better compression during tableting, and also granules with uniform sizes have less chances of segregation after the process of tableting.
The process of granulation can be divided into 3, they are dry granulation, wet granulation and direct compression. In dry granulation, the primary powder is aggregated by applying high pressure onto it. There are two main processes to be chosen ,either a large slug is formed in a heavy duty tableting press (slugging) or a sheet of pressed materials are formed from the direct squeezing of materials between two rollers (roller compaction). These slugs and materials’ sheets are considered as intermediate .These intermediate products are then broken down using a suitable milling method to produce granular material which is then sieved to separate the desired fraction range. The fine powder left may be reworked to avoid waste. There is no fluid involved in dry granulation.
Wet granulation involves the mixing of dry primary powder particles together with fluid which consisting of binder and a suitable solvent .The solvent of the binder must be volatile so that it can be removed easily upon drying. Typical liquids include water, ethanol and isopropanol either alone or in combination. Water is commonly used for economical and ecological reasons. However it has certain disadvantages such as it may adversely affect drug stability, causing hydrolysis of susceptible products besides that it also needs a longer drying times than organic solvents due to its’ high boiling point. In wet granulation the powders is well mixed before an appropriate amount of binder solution is been added. A small lump of wet powder is grabbed using hand and then this lump of wet powder is broken into two pieces to see whether it manage to break smoothly without any fragmentation, if this is achieved, complete granulation and appropriate amount of binder solution is said to be added. All the wet powder mass is then make into a big round lump and then sieved into small wet granules using selected sieve. The wet granules are then dried using oven. The dried granules formed are then sieved the second time to separate out the fine from the dried granules.
Direct compression method is similar to dry granulation method it does not need any binder solution. The dry powders and its’ excipient are compressed directly using puncher. Compression caused the temperature of powders to be increased, the heat energy will melt some portion of the powders into molten state, the adjacent powders are then able to fuse together. When the punch is raised up after compression, heat energy from the powder is lost to the environment, and the fused molten powder will be able to recrystallize back into a larger granules of uniform size
2. Results and calculations
A) calculation of the amount of dry binder added per tablet
Density of binder solution= 2.8gm/ml
Percentage of binder solution= 6 %
Volume of binder solution added= 8ml
Weight of binder solution added= density x volume
=2.8 x 8= 22.4gm
Amount of dry binder added= weight of binder solution added x ( % of binder solution/100)
= 22.4 x 0.06
=1.344gm
Amount of dry binder per tablet = total amount of dry binder/ (500 tablets)
=1.344/500= 2.688 x10-3 gm = 2.688 mg dry powder per tablet
B) Calculation of the percentage of granules.
Percentage of granules= [weight of granule/ ( weight of granules + weight of fines)] x100%
=[62.65/(62.65 +22.36)] x 100 = 73.7%
Percentage of fine= [weight of fine / ( weight of granules + weight of fines) ] x 100%
=100- 73.70=26.3%
**weight of granule: those collected above the sieve after the second sieving.
**weight of fine: those collected below the sieve after the second sieving.
C) Percentage of moisture content of our granules
100- 96.62 (get from moisture balance)= 3.38%
3. Discussion
In this session ,I will basically discuss on the mechanism of wet granulation formation and also the analysis of my results.
The mechanism of fine powdres granulation varies from equipment to equipment. However the proposed granulation mechanism can be divided into 3 stages, first is nucleation, second is transition, and the last stage is ball growth. There are four types of ball growth namely coalesence, breakage ,layering, and abrasion transfer.
During nucleation the particle adhere due to the formation of liquid bridges this is the initial step of granulation because the adhered particles serves as a base for further enlargement of granules.
Enlargement of nucleus takes place when individual particle adhere to the nucleus ;or two or more nuclei combine among themselves. These enlargements of nuclei to form granules are known as transitions.
If agitation is continued, an un-usable, over-massed granules will be formed, these granules are too large for pharmaceutical purposes. Thus the granulation should always be stopped at an optimum point.
There are four possible mechanisms of ball growth, there are coalescence ,breakage ,layering and abrasion. Coalescence is a process by which two or more granules join to form a larger granule. Breakage is said to be happened if granules break into fragments which adhere to other granules, forming a layer of material over the surviving granule. Layering is a process in which a second batch of powder mix is added to a bed of granules, the powder will adhere to the granules, forming a layer over the surface and increasing the granule size. Abrasion is a process by which some portions of a granule are worn off from the surface and bind to other granules, increasing their size. This usually happens during agitation and transferring of the granules.
In our experiment we are actually using wet granulation method. Wet granulation involves the usage of granulation fluid .This granulation fluid is actually a binder solution, in our case we are using maize solution as a binder. The granulation fluid contains a solvent that must be volatile, so that it can be removed by drying.
During wet granulation, binder solution is added to powder bed and is distributed as films around and between the particles. The liquid (water) is distributed between particles in three states namely, pendular, capillary and funicular state.
Addition of a binder solution caused the formation of liquid films around the particles , this effectively decreases the bond distances between adjacent particles. The bond strength between particles are increased. Pendular marks the initial stage of liquid addition where liquid bridges begin to form. At thios point granules have lowest mechanical strength. Further addition of liquid leads to coalescence of the bridges to give the funicular stage. In the capillary stage the void spaces within the granule is replaced with the liquid. Force within the granule is a combination of interfacial forces as well as negative capillary pressure. At this point the amount of binder solution added is said to be optimum, excessive addition of liquid produces the droplet stage, in this stage there will be no intragranular forces, granulation failed to happen
Now I am going to discuss on the results we get from this experiment. The percentage of fine we got was around 26.3 %, which is relatively high. This tells us that the binding of powders are not strong enough and therefore the granules we got can be easily segregated. This may be due to the amount of binder solution we used was too little or it may be due to other factors like inappropriate type of binder used or the distribution of binder solution was not uniform, some powders may not receive any binder solution. These fine powders can actually be collected and recycled so that they can form granules. To reduce the amount of fine and to increase the percentage of granules, we should make sure that the binder solution we use is appropriate and suitable for our materials. It is also important for us to determine the optimum volume of binder solution to be used, since too little or too much of binder solution can lead to loose binding of our powders and the granules may not formed or if it formed it will be too fragile and segregate easily. Since in our case the volume of binder solution used was 8ml, we can actually increase the volume of binder used to 10ml in order to improve the process of granulation. The percentage of moisture content of our granules is 3.38% which is within the range of 3-4%, so we can actually say that our drying process of granules formed is pretty well.
4.Conclusion
1. The amount of binder solution used in this experiment is 8ml ( 2.688mg per tablet)
2. The percentage of granules formed is 73.7%
3. The percentage of fine is 26.3%
4. The moisture content of our granules is 3.38%
5. The Amount of binder solution used can be increased to 10 ml in order to increase the percentage of granules formed. Besides that the mixture of binder solution with powders must be improved, so that the binder solution can get into all the void spaces of our powders for better granulation. If these still don’t work then we can consider choosing a better binder.
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