Pharmaceutics IV PHR4308 Practicals Handbook

Transcription

1 DEPARTMENT OF PHARMACY UNIVERSITY OF MALTA Name: Group: Pharmaceutics IV PHR4308 Practicals Handbook Practical 1: Buffering Pharmaceutical Preparations Practical 2: Industrial Practice 1: Weighing and Dispensing Techniques Dimensions and Friability Testing Practical 3: Industrial Practice 2: Particle Size Distribution Pharmaceutics Co-ordinator: Professor Anthony Serracino-Inglott Compiled by Marie Clare Zammit January 2011

2 Practical 1 BUFFERING PHARMACEUTICAL PREPARATIONS Name: Group: Date: AIM Investigation of the buffering capacity of systems of interest to the pharmaceutical industry. APPARATUS Beakers 4 x 100ml Burette 1 x 50ml Electronic balance Magnetic stirrer Measuring cylinder 1 x 50ml ph meter MATERIALS Boric acid Citric acid Phosphoric acid 2g/100ml Potassium Dihydrogen Phosphate Sodium Hydroxide 0.1M Sodium Hydroxide 0.5M WARNING: The ph meter electrode is very fragile. Handle with care. Always rinse well with water after using it. Leave in fresh distilled water when ready. METHOD i. Accurately weight about 2.01g of citric acid. ii. iii. iv. Dissolve in 50ml water using the magnetic stirrer. Place the ph meter electrode in the solution making sure that the stirrer does not hit the electrode bulb (lower end of electrode) When the ph is steady take the reading. v. Keeping the electrode in the citric acid solution and the solution stirred, add 1ml of 0.5M vi. sodium hydroxide solution from a burette making sure that the sodium hydroxide goes directly in the solution. When the ph is steady, take the reading. vii. Keep repeating step 5 and 6 until the ph is above 12. viii. ix. Accurately weight about 0.155g of boric acid and repeat steps 2 to 7 using 0.1M sodium hydroxide. Continue until the ph is above 11. Take 50ml of the phosphoric acid provided in a beaker and place on the magnetic stirrer. MCZ/ASI 11 2

3 x. Place the ph meter electrode in the solution making sure that the stirrer does not hit the electrode bulb. xi. When the ph is steady take the reading. xii. Keeping the electrode in the solution and the solution stirred, add 1.0ml of 0.5M sodium hydroxide solution from a burette making sure that the sodium hydroxide goes directly in the solution. xiii. When the ph is steady take the reading. xiv. Keep repeating steps 12 and 13 until the ph is above 11. xv. Accurately weight about 0.354g of potassium hydrogen phosphate. xvi. Dissolve in 50ml water using the magnetic stirrer. xvii. Place the ph meter electrode in the solution making sure that the stirrer does not hit the electrode bulb. xviii. When the ph is steady take the reading. xix. Keeping the electrode in the solution and the solution stirred, add 1.0ml of 0.1M sodium hydroxide solution from a burette making sure that the sodium hydroxide goes directly in the solution. xx. When the ph is steady, take the reading. xxi. Keeping repeating steps 19 and 20 until the ph is above QUESTIONS 1. What is the molarity of each of the solutions used? Calculations Solution Boric acid Citric acid Phosphoric acid 2g/100ml Potassium Dihydrogen Phosphate Molarity 2. Plot a graph of ph against volume of sodium hydroxide added for each solution. Comment on the graphs obtained. MCZ/ASI 11 3

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8 3. What is meant by buffering capacity and how could the graphs obtained in 2 be related to it? 4. Using a mixture of the buffers studied, how would it be possible to have a buffer capable of buffering between ph 2 and ph 9? 5. Discuss the use of buffers in the pharmaceutical industry. MCZ/ASI 11 8

9 REFERENCES 1. Billany MR Solutions. In Aulton ME, ed. Pharmaceutics, The science of dosage form design, New York: Churchill Livingstone, 1988: British Pharmacopeia. London: Her Majestys Stationary Office, Volume : Food JL. Parenteral Products. In: Aulton ME, ed. Pharmaceutics, The science of dosage form design, New York: Churchill Livingstone, 1988: Harvey SC. Blood, fluids, electrolytes and haematological drugs. In Gennaro AR, ed. Remington s Pharmaceutical Science. 18 th ed. Pennsylvania: Mack Publishing Company, 1990: Martin A. Physical Pharmacy. 4 th ed. Philadelphia: Lea and Febiger, 1993: Mullins JD, Hecht G. Ophthalmic preparations. In Gennaro AR, ed. Remington s Pharmaceutical Science. 18 th ed. Pennsylvania: Mack Publishing Company, 1990: Niebergall PJ. Ionic solutions and electrolyte equilibria. In: Gennaro AR, ed. Remington s Pharmaceutical Sciences. 18 th ed. Pennsylvania: Mack Publishing Company, 1990: , Richards JH. Solutions and their properties. In: Aulton ME, ed. Pharmaceutics, The science of dosage form design, New York: Churchill Livingstone, 1988: 45. Demonstrator Name Signature MCZ/ASI 11 9

10 Practical 2 Industrial Practice 1a: Weighing and Dispensing Techniques Name: Group: Date: Dispensing in a manufacturing plant is performed in accordance to Good Manufacturing Practice (GMP). The persons performing the operation will follow a written approved procedure and a number of checks are normally performed before, during and after the actual weighing of raw materials. i. Check the status of the dispensing area. Record your findings below, deleting as appropriate. The dispensing area is clean / not clean. Sign Date ii. In industry, you would be performing such an activity under a laminar or cross-flow hood fitted with filters. In this case, you would normally be required to check that the resistance to flow through the hood is within limit. A high reading would indicate that: What action would you take? A low reading would indicate that: What action would you take? iii. Record the operation being performed on the area log: Room / Area: Activity: Performed by: Supervised by: (sign/date) (sign/date) MCZ/ASI 11 10

11 Questions 1. Briefly explain the difference between an expiry date and a retest date. 2. With reference to EU-GMP, state why two signatures were required in various instances of this operation. 3. Briefly explain what a Batch Manufacturing Record (BMR) is. 4. What is the significance of an item number and of a batch number? What is the difference between them? 5. A pharmaceutical manufacturing company uses lactose monohydrate in ten of its solid dose formulations which were manufactured using wet granulation techniques. A new direct blend product is being developed by its R&D department which again requires lactose monohydrate. However, the lactose monohydrate to be used in this formulation is of a different specification. Briefly describe the systems that assure the correct grade will be used in the respective products in manufacture. Will testing the incoming material to the pharmacopoeial monograph alone provide sufficient reassurance that the new material meets the specifications set by the R&D Department? If not, what other tests will be required? MCZ/ASI 11 11

12 Industrial Practice 1b: Dimensions and Friability Testing Using a micrometer screw gauge, record the diameter and thickness of 6 tablets. Tablet Diameter Thickness i. Compare the results obtained with the limits for the sample, which have been displayed by the demonstrator on the white board. Does the sample meet the requirements with respect to dimensions? Calculations ii. Can you get variation in diameter during the production of a batch of tablets? Can you get variation in thickness during the production of a batch of tablets? Briefly explain your answers. a. One of the tests used to measure the strength of a tablet is friability. This test is of particular importance for tablets which tend to cap on attrition. iii. iv. Examine the tablets you have been provided with. If they are dusty, place them on a coarse sieve and dust them lightly with a soft brush. Accurately weigh an amount of tablets which is as close as possible to 6.5g. Record this weight as W 1. W 1 MCZ/ASI 11 12

13 v. Place the tablets in one section of the friabilator. vi. vii. Switch on the friabilator and rotate 100 times. Carefully transfer the tablets to a coarse sieve and dust lightly with a soft brush. Weigh the tablets and record this weight as W 2. W 2 viii. Calculate the friability as follows: Calculations a. Friability = (W1 W2) x 100 % W1 ix. Compare the results obtained with the limits for the sample, which have been displayed by the demonstrator on the white board ( 1.0%). Does the sample meet the requirements with respect to friability? x. What problems do you envisage if the tablets have a high friability? Demonstrator Name Signature MCZ/ASI 11 13

14 Practical 3 Industrial Practice 2: Particle Size Distribution Name: Group: Date: Powders generally consist of particles with irregular shapes and non-uniform sizes. This means that size distributions are often complex. Particle size is therefore described by determining the number of particles in successive size ranges. The distribution is often represented by a histogram in which the width of the bar represents the size range and the height represents the frequency of occurrence in each range. A smooth curve can then be drawn through the midpoints of the tops of the bars. A particle size distribution curve is obtained in this way. In order to obtain this curve, the powder is separated into fractions depending on particle size. The method most often used for this is by sieving. Basically, this technique consists of placing a nest of sieves of different aperture on top of one another with the finest aperture sieve being placed at the bottom and subsequent sieves being placed in a ascending degrees of coarseness. The sieves are then shaken mechanically or electromagnetically. The sieve motion applied can be oriented horizontally which tends to loosen the packing of the particles in contact with the sieve surface, or vertically which tends to agitate and mix the particles. Method i. Accurately weigh each sieve you will be using to the nearest 0.1g. ii. iii. iv. Set up the nest of sieves on the mechanical shaker so that the finest sieve is at the bottom and the coarsest sieve is on top. Accurately weigh out approximately 25g, 50g and 100g of the powder. Place the first sample carefully on the topmost sieve and close the cover. v. Shake the powder through the sieves at 50% amplitude for 5 minutes. Then clean the sieves and repeat for each sample size so as to determine what sample size should be used. vi. vii. viii. Accurately weigh the approximate sample size to be tested. Clean and accurately weigh once again each sieve. Place the sample on the top most sieve, close the lid and vibrate at 50% amplitude until the end-point is reached. This is achieved when the weight held on each one of the sieves does not change by more than 5% or 0.1g (or 20% if the weight on that particular sieve is less than 5% of the test sample size). If any sieve is found to hold more than 50% of the test sample, then the test is to be repeated with the inclusion of an additional sieve of intermediate coarseness between this sieve and the next coarser one. You should repeat the test if more than 5% of your sample is lost. Your report must include the total sieving time, the methodology used (Dry Sieving Method) and the set values for all variable parameters. MCZ/ASI 11 14

15 Questions 1. Draw a histogram of your particle size distribution and a particle size distribution curve. Comment on the shape of this curve. Comment on the shape of this curve. MCZ/ASI 11 15

16 2. What is the finest particle size you would normally use this method for? 3. What problems can be encountered if the particle size is finer than this? 4. Which standard describes how to calibrate test sieves? 5. What would you use to check the effective opening of test sieves? 6. What is the commonest difficulty encountered when testing particle size by this method? How can this problem be overcome? 7. What settings can be varied in this test? MCZ/ASI 11 16

17 8. Apart from mechanical and electro-magnetic shaking, what other method of oscillation can be used? 9. How should sieves be cleaned? 10. If electrostatic charge is affecting your analysis, what corrective action should you take? 11. An R&D facility has obtained a very limited amount of an API which is very scarcely available. The particle size of this material needs to be assessed. Would you use 200mm diameter sieves or 76mm diameter sieves in this case? Demonstrator Name Signature MCZ/ASI 11 17