CH314 - Experiment 2 PDF

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Experiment 2: Determination of the Dissolution Rate of Aspirin from Tablets Date: 23 Oct 2020 Introduction: Tablet dissolution is the process in which a drug dissolves and forms a solution. Dissolution testing measures the rate and the degree of dissolution for a variety of dosage forms including tablets, capsules, dermal patches, creams and ointments. The importance of dissolution testing is seen in how it relates to the drug delivery and bioavailability in the body. Sufficient quantities of the API (Active Pharmaceutical ingredient) must dissolve in the body to allow for absorption in the bloodstream (must be bioavailable) for the drug to be effective and carry out its function. Too little dissolution (i.e low concentration in the bloodstream) will not produce a response in the body and too much may be toxic. To properly test the dissolution of drug products, the procedure must be standardized. It helps ensure quality in production of the drug. USP has set standard test for this in chapter . Many factors affect the dissolution rate, including dosage form, size, shape, excipients and their properties, pH, temperature and tablet hardness. When designing a drug product, these factors must be considered to ensure the maximum dissolution of the API to allow maximum efficiency of the drug. In this experiment, the dissolution of aspirin is measured. Aspirin has a known maximum UV absorbance at around 260. The concertation of aspirin of each sample taken can be deduced by measuring its absorbance at 260 nm, hence the rate of dissolution can be calculated.

Experimental Method: 7 1-litlre vessels were placed in a water bath kept at a constant temperature of 37oC. 0.05M phosphate buffer was heated to 41oC with constant stirring. The solution was filtered through a 0.45μm filter into a flask with a stirring device. The flask was sealed and a vacuum was applied for an additional 5 minutes to remove any air. This solution was made sure not to drop below 37oC before initialisation of the test. 900ml of the phosphate buffer was added into each of the 7 vessels in the water bath. Once the media (phosphate buffer) has equilibrated to a temp of 37oC, an aspirin tablet was dropped into six of the seven vessels. (the media in vessel without the tablet was used to replace the aquilots taken out of the other vessels). A timer as set as soon as the tablets were placed in the vessels.

Samples were taken out of each vessel with a syringe at time intervals of 1, 5, 10, 15, 20, and 25 mins, each time replacing the media with the one from the vessel without any tablets. The absorbance of the samples taken were measured using a UV spectrometer at 260nm, as well as a standard solution of aspirin with a concentration 32.5mg/100ml.

Results: 1. The label of the tablets tested claimed each tablet contains 325mg of aspirin and 15mg of caffeine. 2. The absorbance values of the samples collected are shown in table 1 below. Table 1: Absorbance values for samples taken Time (mins) 0

Absorbance @ 260nm 0

% Dissolution 0

1 5

0.339 0.537

26.57665505 42.09930314

10 15

0.716 0.799

56.13240418 62.63937282

20 25

0.877 0.997

68.7543554 78.16202091

The % dissolution is given by: 𝐴𝑏𝑠𝑟𝑜𝑏𝑎𝑛𝑐𝑒(𝑠𝑎𝑚𝑝𝑙𝑒) × 𝑤𝑒𝑖𝑔ℎ𝑡 (𝑠𝑡𝑑 ) × 𝑠𝑎𝑚𝑝𝑙𝑒 𝑣𝑜𝑙𝑢𝑚𝑒 × 100% 𝐴𝑏𝑠𝑜𝑟𝑏𝑎𝑛𝑐𝑒 (𝑠𝑡𝑑) × 𝑣𝑜𝑙𝑢𝑚𝑒(𝑠𝑡𝑑) × 𝑊𝑒𝑖𝑔ℎ𝑡 (𝐿𝑎𝑏𝑒𝑙 𝑐𝑙𝑎𝑖𝑚) The standard solution had a concentration of 32.5mg/100ml. The absorbance of the solution was recorded to be 1.148. The weight of aspirin stated on the label was 325mg. The sample size was taken as 900ml. 3. A plot of the results in table 1 gives the graph shown in figure 1.

% Dissolution

Plot of % Dissolution as a function of time 100 90 80 70 60 50 40 30 20 10 0 0

5

10

15

20

25

Time (mins)

30

35

40

45

Figure 1: Graph of % dissolution vs. time

4. From the graph in figure1, we can estimate the time it would take for 100% dissolution by extending the curve. This would give an approximate value of 45 minutes. 5. Before the tablets are placed in the bath, the temperature of the media in the vessel should be checked to ensure that it is 37oC ± 0.5oC. The pH of the media must also be checked so that it within specification. The media in each vessel must also be equal in volume. 6. In this test, the pH of the media was around 7. This value represents the pH of blood in the body. The test conditions are meant to mimic the environment in the bloodstream. 7. As samples were taken out of each vessel, it was replaced with aliquots from the vessel without a tablet. This is to ensure that the volume of each vessel remains constant.

Discussion: 1.

As seen in figure 1, there is a sharp increase in the dissolution as the tablet is introduced into the buffer. As time carries on, the tablet dissolves in almost a linear rate.

2.

Factors that affect the rate of dissolution: • Tablet size: The larger the tablet, the more surface there is. A larger surface area will allow for more contact with the media and thus a faster rate of dissolution. • Tablet formulation: Tablets formulated with smaller granules will have an increased dissolution rate. As these granules break away from the main body of the tablet, there is an overall increase in surface area exposed to the medium. • Tablet hardness: Tablet hardness is related to the friability of the tablet. With low hardness and a high friability, the tablet will dissolve more in the media. Hence it will have a faster rate of dissolution.

3.

In this experiment, the Q value is taken as 85% of active ingredient released after 40 minutes. The acceptance criteria for each stage can be deduced from table 2 under USP guidelines: Table 2: Acceptance table for Q Stage Number tested S1 6 S2 6

Acceptance criteria Each unit is not less than Q + 5% Average of 12 units (S1 +S2) is equal to or greater than Q, an no unit is less than Q - 15%

S3

12

Average of 24 units (S1 +S2 +S3) is equal to or greater than Q, not more than 2 units are than Q - 15%, and no unit is less than Q - 25%.

Hence the acceptance criteria for each stage is as follows: S1 – 6 units tested. Each unit is not less than 90% S2 – 6 additional units tested. Average of 12 units (from stage 1 and stage 2) is equal or greater than 85%, and no unit is less than 70% S3 – 12 additional units tested. Average of 24 units (stages 1+ 2+ 3) is equal to or greater than 85%, not more than 2 units are less than 70%, and no unit is less than 60%. Looking at the plot in figure 1, at 40 mins the average dissolution for each tablet is 94%. This is within the acceptance criteria for stage 1.

4.

The time for complete dissolution of the drug is an approximate value derived from the plot in figure 1. A more accurate way to find the time for 100% dissolution would be to carry out the experiment for a longer length of time. If the experiment was allowed to continue past the point of complete dissolution, the exact time that the tablet is completed dissolved can be obtained. A more accurate plot can also be obtained by taking samples from the vessels at smaller time intervals. The shape of the curve between the points in figure 1 will be more representative of the dissolution rate, rather than an approximation....