The compressed tablet is by far the most popular and versatile dosage form however it does have its drawbacks, in that it is the most technically difficult to form. Tablets are made by a process of compression. A variety of tablets exist and the type of excipients and the way in which they are incorporated vary between dependent on type and size. The powder formulation is contained within a set volume and force is applied via punches to form a solid compact. The first attribute of a tablet formulation is therefore compressibility.
The second attribute is good flow. Tablets are controlled by weight. After all, the drug dose is a weight included in a larger weight contributed by excipients. The process of tableting relies on consistent volumetric filling of the die space set by the bottom punch. Most drugs are poorly compressible and form ‘lumpy’, cohesive bulk. To achieve the necessary attributes of good flow and compressibility for successful tableting, drug substances inevitably have to be combined with other excipients.
Aim[h] The aim of this experiment was to formulate and manufactured Aspirin 75mg tablets in direct compressions. There were also a number of tests undertaken to assess the quality of the tablets produced, ensuring that the dosage forms met the required Pharmacopoeial standards. As identified below the experiment was broken down into three stages to enable the group to undertake the practical over a period of time and within different places.
1. Formulation/Granulation 2. Manufacture 3. Testing Direct Compression (DC) Generally, direct compression is deemed a simpler method than wet granulation. It only involve in two operations in sequence: powder mixing and tableting compression directly from powdered formulations without changing the physical properties of the material used. As a heat and water are not involved in DC and this improve product stability. It is used for relatively potent which are present in a few mg in each tablet and can be mixed with relatively coarse excipient particles and soluble drugs which can processed as coarse particles and this ensure good flowability. However, in a direct compactable formulation, specially designed fillers and dry binders are normally required.
Advantages of using direct compression over granulation include; being more economical, requiring fewer materials and staff, it can be prepared in stages, less space and time are required compared to wet granulation and it doesn’t involve heat and moisture. It mainly contains microcrystalline cellulose (MCC) which is able to self-disintegrate, hence, requires less lubricant. The therapeutic effect of the formulation is more quickly achieved in DC while granulation delays the duration taken to attain therapeutic effects.
Despite the many advantages of DC, it is important to note that it does have some disadvantages. For example; it is not ideal for poorly compactable large dosage drugs and it is complex to formulate small to medium dose drugs as these have a small final weight. Furthermore, the static electricity used can result in segregation of the DC tablet. The physically modified properties of the filler blinders demand tight control. There is a lack of content uniformity for low dose drugs. The accumulation of dust is also an issue.
Wet Granulation Wet granulation is the most commonly used manufacturing process for oral dosage forms. The purpose of granulation is to enable primary powder particles to adhere to form multi-particulate entities known as granules. Wet granulation is a commonly performed method of granulation. A planetary mixer is initially used to mix the powder (dry) to achieve good homogeneity, at a high intensity. However, wet granulation remains the most robust manufacturing method. It is the method that has the ability to mask the variability in the properties of the incoming raw materials, thus to ensure a robust and a predictable performance.
Wet granulation accumulates less dust during powder handling than direct compression method. Granulation improves both the compaction characteristics and flow properties of a mix and is able to prevent segregation of the constituents of the mix. However, wet granulation is not appropriate for water or heat sensitive drugs and this lead to poor chemical stability or unpredictable drug product performance.
All excipients where weighed [j]using analytical balance within 1% +/- (g) required mass which illustrated within the table above. All the mixed of diluents, filler, disintegrant, glidant and the aspirin were transfer into a jar of tumble mixer and mixed for 2 minutes. The mixture was sieved in a 500 micron and then transferred back into a tumble mixer for 2 min. The mixture was sieved again with the aid of a plastic card and finally was transfer back into the tumble mixer.
2. TABLET MANUFACTURE[k]
The Manesty F3 single-station tablet machine was used to compress the previously prepared formulations into 300 mg tablets. The tooling was used 10 mm concave punch and die set. The lubricant used had been saved from our last experiment. Prior to compression, tablet formulation requires lubrication. In order to ensure that the formation and ejection can occur with low friction. The required amount of lubricant was added and was blended for 5 min. The tablet machine was set up with the compression tooling which were the upper punch, lower punch and dies and this was to familiarise how the operation work and the ways in which the tablet weight and how compression force were controlled.
The fill depth of the die was adjusted by altering the capacity regulating screw so that the tablet weight is approximately 300 mg. Target tablet weight is 300mg (± 15mg). A tablet was then compressed by manually turning the fly-wheel. The tablet machine was turned on in order to compress 40 tablets at two different compaction forces, 5KN and 10KN (low and high), they were then stored for the next practical Tablet Testing. The amount of powder (300mg) filled into the die is controlled by the position of the lower punch. The upper punch descends and exerts compression force of 10Kilo Newton. After ejection, the tablet is pushed down to a basket by the hopper shoe. 50 tablets per batch were produced and all settings remained the same[l].