EXAMINATION PAPER: ACADEMIC SESSION 2008/2009 Programme Course Title Course Code Stage Date and Duration Paper

Set by MPharm MP2: Medicine Design and Manufacture 2 PHAM1055 TWO May 2009, 3 hours
Dr Calzolai, Dr Corlett, Dr Ghafourian, Dr Kallinteri, Dr Nokhodchi, Dr Sumbayev

INSTRUCTIONS TO CANDIDATES: You must start a new answer sheet for each question answered and ensure that you insert your banner identity number only (NOT your name) at the top of each answer sheet.
THE PAPER IS DIVIDED INTO TWO SECTIONS. SECTION A: Answer ALL questions - 30% weighting Allow 1 hour to complete this section. SECTION B: Answer FOUR out of SIX questions - 70% weighting Allow 2 hours to complete this section.

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Date and Duration of Exam: Course Title: Course Code: May 2009, 3 hours MP2: Medicines Design and Manufacture 2 PHAM1055 Page 1 of 5 2009 Medway School of Pharmacy

SECTION A Answer all FIVE questions Question 1 State the stages for sugar coating and discuss the sealing of the tablet core. [6 marks]

Question 2 Discuss the requirements, potential use and coating faults of press coating. [6 marks]

Question 3 Discuss the reasons why a sieving technique should be avoided for the measurement of particle size distribution of certain powders. [6 marks]

Question 4 TM, a 35 year old healthy male volunteer, was given a loading dose of drug X of 4 mg by intravenous bolus. At the same time a continuous intravenous infusion of drug X was started at a rate of 0.7 mgh-1. Serial plasma samples were taken, and from these the half-life (t) and volume of distribution (v) were determined (Table 1). a) Copy out and complete the table by calculating the elimination rate constant (k), clearance (CL), concentration at zero time (C0), and concentration at steady state (Css) for TM. b) Sketch the plasma concentration versus time curve for the first 48 hours of his treatment. Illustrate the contribution of the IV bolus dose and the constant infusion to the plasma concentration over this time period. Table 1: Pharmacokinetic parameters for TM V (L) 287 t (h) 4 k (h-1) CL (Lh-1) C0 (gL-1) Css (gL-1) [6 marks]

Question 5 Describe the factors affecting drug metabolism and give at least one example for each factor. [6 marks]

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Date and Duration of Exam: Course Title: Course Code: May 2009, 3 hours MP2: Medicines Design and Manufacture 2 PHAM1055 Page 2 of 5 2009 Medway School of Pharmacy

SECTION B Answer FOUR from the SIX questions Question 6 a) A pharmaceutical company has designed a new formulation for ibuprofen tablet as follows: Ibuprofen 200 mg Starch 10 mg Lubricant 20 mg

The results showed that the hardness of the tablets was very low. State the options to increase the hardness of ibuprofen tablets (ibuprofen particles undergo plastic deformation during the compression). [4 marks]

b) Considering the rectangular particle below, calculate circularity of the particle. Assume the radius of the circumscribed circle for this particle is 10 m. [4 marks]

c) You are the responsible person for controlling the weight variation of diazepam tablets. The weight of 10 tablets is listed in the following table. Should this batch be rejected? Justify your answer. [6 marks] Tablet Weight of tablets (mg) number 1 105 2 116 3 95 4 104 5 95 6 105 7 90 8 100 9 90 10 100

d) Discuss the disadvantages of the wet granulation technique.

[6 marks]

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Date and Duration of Exam: Course Title: Course Code: May 2009, 3 hours MP2: Medicines Design and Manufacture 2 PHAM1055 Page 3 of 5 2009 Medway School of Pharmacy

Question 7 (2 normal graph papers may be needed to answer this question) The following particle size data were obtained using a microscope counting technique Particle size Number of particles --------------------------------------------50 6 100 10 150 20 200 40 250 50 300 40 350 20 400 10 450 4 -------------------------------------------------------------------a) b) c) d) Plot particle size distribution (use the graph paper provided) Plot cumulative undersize against particle size. Calculate the arithmetic mean particle size diameter. Calculate median and standard deviation graphically. [5 marks] [5 marks] [5 marks] [5 marks]

Question 8 a) What is thin layer chromatography (TLC) and what are the principles by which a mixture of compounds can separate into individual components in TLC? [8 marks] b) Briefly describe high pressure liquid chromatography (HPLC), and the main components of a HPLC instrument. Give also one example of possible application. [12 marks]

Question 9 a) Briefly describe the principles of Infrared Spectroscopy and give one example of its application. [8 marks] b) Which is the molecule that corresponds to the following 1HNMR spectrum? Explain your choice and why you excluded the other molecules. [12 marks]

a) CH3-CHBr-CO-CH3 b) CH3-CHBr-CO-CH2-CH3 c) CH3-CHBr-CH3

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Date and Duration of Exam: Course Title: Course Code: May 2009, 3 hours MP2: Medicines Design and Manufacture 2 PHAM1055 Page 4 of 5 2009 Medway School of Pharmacy

Question 10 a) Discuss the factors affecting dissolution rate of drugs. [10 marks] b) Discuss the factors affecting the gastric emptying time of pharmaceuticals. [10 marks]

Question 11 (2 cycle log linear graph paper may be needed to answer this question) After the oral administration of 100 mg of drug X (oral suspension), the following plasma concentrations were determined. Time after administration (h) 0.25 0.50 1.0 1.5 2.0 2.5 3.5 4.5 5.5 7.0 Plasma concentration (g ml-1) 1.4 2.1 2.6 2.5 2.2 1.9 1.2 0.76 0.50 0.25

a) Define the meaning of the terms bioavailability and bioequivalence. [3 marks] b) Calculate the absorption and elimination half-lives for drug X and determine the AUC(0-) [12 marks] c) Following a suitable wash out period an intravenous bolus dose of 50 mg was given to the same healthy volunteer and serial plasma samples taken. The AUC0- was 15.56mghL-1. Calculate the bioavailability of the oral dosage form of drug X. [3 marks] d) Would you expect this drug to have a high or low extraction ratio? Give reasons for your answer. [2 marks]

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Date and Duration of Exam: Course Title: Course Code: May 2009, 3 hours MP2: Medicines Design and Manufacture 2 PHAM1055 Page 5 of 5 2009 Medway School of Pharmacy