Paracetamol, lactose and the disintegrant were placed into a planetary mixer. Approximately 50mls of PVP (which had previously been prepared as a 15% w/v solution in distilled water) was added gradually while mixing was occurring. Mixing was stopped when the mixture reached a homogenous consistency (or when the particles stuck together when gentially squeezed. The mixture was passed through a sieve of 1mm pore size. The mixture was then placed into a previously weighed metal tray. The tray was then weighed again. The granules were spread evenly on the tray, then placed into an oven at 701i??
C. After twenty minutes, the tray was removed from the oven, the granules were turned over and mixed. The new weight of the tray was recorded, and the tray was again placed in the oven. After a further ten minutes the tray was again removed from the oven, the granules were turned over and the tray weight was recorded, the tray was again replaced in the oven. This process was repeated every ten minutes until the weight of the tray remained constant. Once the granules were completely dry they were passed through a wide meshed sieve to remove aggregates ( the very large particles).
These sieved particles were collected and passed through a fine meshed sieve, with a pore size of 125? m, to remove fines ( the very small particles ). Granules were placed into a tared amber jar and weighed. Magnesium stearate was added (1% of the total weight of the dry granules). This mixture was then placed on a roller mixer for five minutes. Each sieve in the nest of sieves were weighed. 100grams of tared granules were placed in to the nest of sieves. Tapping commenced for ten minutes.* The sieves were then weighed again. Results:
Grade Batch Weight Polyvinylpyrrolidone MW av. 44,000 K28350583046 45g Purified Water Distilled purified water – To 300ml 300mls of solution was prepared, and each group was assigned 50mls. Class interval Frequency Height on histogram 0- base 7 2. 8 250 22 22 350 24 16 500 18 8. 57 710 22 7. 59 1000 3 0. 75 1400 1 0. 3 1700 3 1 From Graph 2, these values can be calculated: Undersize Oversize Lower quartile Medium Upper quartile The height on the histogram was calculated by rearranging the following formula; The inter-quartile co efficient of skewness (IQCS).
IQCS (undersize) = IQCS (oversize) = IQCS values lie between -1 and +1. A value of zero indicates a symmetrical size distribution. Our vale of _____ and _____ indicates a shift away from a normal particle size distribution. This is also reflected on the shape of our histogram, a negatively skewed distribution. However one must remember that a large number of samples is ideally needed. Discussion: From looking at graph 1, it can be seen that a large number of particles are within the size range 250-350? m, but the majority of particles exist are large than this.
According to a definition of particle size grades, particles of this size are classified as corse powders (? 300? m) The histogram has a typical left-shifted distribution. This is a negative distribution, it shows that the majority of particles are in the lower size range. This is turn tells us that the granules contain more fine particles, than course particles for example. Graph 1 also shows us that there is quite a wide variation in the different particle sizes that would be present in the granules. Having different sized particles in a powder, will have an effect on its flow and packing properties.
Different amounts of powder will be compressed into each table, possibly causing irregularities in the dose reaching the patient. In an ideal tablet formulation, the distribution would be normal and uniform. Therefore there would be more regularity in the size of particles in the tablet. Graph two represents the different particle sizes present in our powder. If we read across at 50%, we see the two lines representing oversized and undersized particles intercept. Reading off this value on the x-axis tells us that our mean particle size is 500? m. This graph again shows a very large amount of particle size variation occurring.
Ideally we would like a uniform, continuous particle size, which is normally distributed, because have particles of the same size makes mixing easier and improves the flow and packing properties of powders. When particles of a range of different sizes, the volume of powder compressed into a tablet is not as controlled/ accurate as it would be if they were all the same size. This means may lead to varying dose from tablet to tablet. Error did occur during our manufacturing process, as can be seen from table 1, the amount of magnesium state that was used in preparation of granules using Ac-di-sol (2%) was much higher than other groups.
This value should have been 3. 568g. The results of this practicle are not affected, but the results of the next practicle are likely to be affected as magnesium stearate is very hydrophobic drugs release will be affected. Experimental errors are likely to have occurred. Especially as four different groups were working individually. Variation between the turning and mixing techniques by different groups are probable. Loss of material may also have occurred between transfers (from beakers into mixers and through sieves), such that we do not end up with the amounts that had been accurately measured.