Part ONE. Answer ALL questions. For each questions, there is ONE correct answer. Use the multiple choice reader card provided for ALL your answers.

Transcription

1 UNIVERSITY OF EAST ANGLIA School of Pharmacy Main Series UG Examination PHARMACEUTICAL TECHNOLOGY PHAN2HGY Time allowed: 2 hours Part ONE. Answer ALL questions. For each questions, there is ONE correct answer. Use the multiple choice reader card provided for ALL your answers. Part TWO. Answer THREE (3) of the FOUR (4) questions. Use a SEPARATE answer book for EACH question in Part TWO. Each question has the same value. The marks distribution is shown as a percentage for each section of the question. Answer all parts of each of the individual questions you select. The mark allocation for the paper is: Part ONE carries 30% of the total mark Part TWO carries 70% of the total mark Graph paper for Q32 and Q33 will be provided. This paper consists of 13 pages in total. Notes are not permitted in this examination. Do not turn over until you are told to do so by the Invigilator. Do not take this question paper out of the examinations room. (PHAN2HGY) Module coordinator: Dr Sheng Qi, PHA Copyright of the University of East Anglia Version 2

2 2 Part ONE 1. Which of the following statements is TRUE regarding the influence of particle size and shape on powder properties? A) Particle shapes with a high surface area/volume ratio lead to higher dissolution rates than those with a low surface area/volume ratio B) The dissolution rate of drug powders can be increased by increasing the particle size C) An ordered mix is most easily prepared when mixing two powders with similar particle sizes D) Powders consisting of smaller particles flow more easily than powders of the same material consisting of larger particles E) Solubility differences between polymorphs are observed, because they are made up of particles with different shapes and sizes 2. Which of the following statements is TRUE? When measuring powder flow properties: A) The angle of repose is characteristic of the material and does not depend on the size and shape of the particles B) More than one angle of repose can be seen for powders that flow well C) An angle of repose above 50 indicates that the powder flows freely D) The coefficient of internal friction is equal to the angle of repose E) A Hausner ratio below 1.2 is indicative of good powder flow characteristics 3. Which of the following statements is TRUE? When mixing powders: A) A longer mixing time may lead to a less uniform mixture B) Larger particles tend to accumulate near the bottom of the powder bed after mixing C) When assessing the uniformity of a mixture, testing smaller samples from the mixture will show a more uniform mixture D) Powders that flow well are less likely to segregate E) Agitator mixers are used to gently blend lubricants and glidants into powder mixtures

3 3 4. Which of the following statements is TRUE regarding methods of particle size determination? A) Optical microscopy can be used to determine the equivalent volume diameter of particles B) Laser diffraction can be applied in the 1 μm 1000 μm size range C) Laser diffraction is based on the principle of Brownian motion D) Sieving can measure particle size distributions down to about 4.5 μm E) Coulter counters can only be used for powders that are insoluble in electrolytes 5. Which of the following statements is FALSE concerning drug hydrolysis? A) Hydrolysis is catalysed by both acids and bases B) The stability of solution formulations towards hydrolysis can be increased by the addition of less polar solvents to an aqueous solution C) Hydrolysis reactions generally show (pseudo-)first order kinetics D) Esters tend to be more stable towards hydrolysis than amides E) Hydrolysis may cause degradation in formulations that do not contain water 6. Which of the following statements is FALSE? When considering the physical stability of pharmaceutical formulations: A) Transformation to a more stable drug polymorph can reduce the efficacy of solid formulations B) Breaking or cracking of tablets influences their dissolution and disintegration properties C) Particle aggregation in suspension formulations will increase the bioavailability of the drug D) Precipitation from a solution formulation reduces the reliability of dosing E) Materials released from the packaging into the dosage form are called extractives 7. Which of the following statements is TRUE regarding reaction rates? A) The half-life of second order reactions is independent of the concentrations of starting materials B) Radioactive decay is a zero order reaction C) The rate of a first order reaction is proportional to the concentration of the reaction product D) A second order reaction will appear to follow first order kinetics if one of the reactants is present in a large excess E) The rate of a first order reaction remains constant until the reaction proceeds to completion TURN OVER

4 4 8. Which of the following statements is FALSE concerning core tablet formulations? A) Lactose monohydrate is used as a diluent B) Microcrystalline cellulose is used as glidant C) Polyvinyl pyrrolidone is used as a binder D) Magnesium stearate is used as a lubricant E) Pregelatinised starch is used as a disintegrant 9. Which of the following statements is FALSE concerning tablet formulation? A) Mannitol can perform as diluent B) Low concentration ingredients can be contained in the granulation fluid C) HPMC is normally added in the granulation fluid as binder D) Superdisintegrant is required in lower quantities than the standard type E) Avicel PH101 is a typical compression aid 10. Which of the following statements is TRUE concerning the wet granulation process? A) "Overgranulation" may lead to disintegration during drying B) "Undergranulation" may lead to forming a slurry C) Water is the granulation solvent of choice D) The drug is normally mixed in the granulation fluid E) The wet granules should be dried for as long as possible 11. Which of the following statements is TRUE with respect to radioactivity? A) Two positrons will combine to produce a gamma ray B) Beta particles are mono-energetic C) X-rays are produced as a result of electron capture D) Gamma rays arise from outside the nucleus of the radioactive atom E) After alpha emission, the atomic number of the daughter nuclide is the same as the parent nuclide 12. Which of the following statements is TRUE in terms of direct compression? A) High drug concentration may cause problems with homogeneity B) Plastic deformation significantly increases the total particulate surface area C) Excipients are spray-dried to ensure sphericity, good mixing and flowability D) Brittle fracture makes it easy to remove the tablet from the die E) Microcrystalline cellulose shows brittle fracture

5 5 13. Which of the following statements is FALSE in terms of tabletting? A) A compression station consists of one die and two punches B) The lower punch moves only to eject the tablet C) Single-station presses are used for research and development while multistation presses are applied for production D) Capping is caused by excessive elastic recovery E) For a single station press, the force is applied by both punches 14. Which of the following statements is TRUE? Water content in a solid sample may be expressed as: A) Relative humidity B) Equilibrium hydrate content C) Dew point D) Moisture content E) Vapour pressure 15. Which of the following statements is TRUE concerning spray drying? A) Involves reducing the liquid to atoms B) Is used to dry wet solids C) Is used to prepare solids from liquids D) Tends to produce cylindrical particles E) Tends to produce solid spheres 16. Which of the following is FALSE? Freeze drying: A) Involves the application of high pressure to a liquid B) Involves sublimation of ice C) May include cryoprotectants such as glycerol D) Produces porous solids E) Must be performed below the T g of the material 17. Which of the following statements is TRUE in terms of crystal structure? A) Nucleation may be homogeneous or heterogeneous B) There are nine types of basic unit cell C) Crystallisation takes place from saturated solutions D) The dimensions of a hexagonal unit cell are all identical E) The unit cell repeats itself in two dimensions to form the complete crystal TURN OVER

6 6 18. Which of the following statements is TRUE? The crystal habit of a drug: A) Describes the polymorphic form of the drug B) Is unaffected by crystallisation conditions C) Is an indication of the degree of hydrophobicity of the drug D) Is usually triclinic, monoclinic or orthorhombic E) Describes the external shape of the crystal 19. Which of the following statements is TRUE in terms of pharmaceutical hydrates? A) The term hydrate describes the total water present within the sample B) A hydrate has water associated with the unit cell in a defined ratio C) Hydrates may contain water or organic solvents D) Hydrates may be enantiotropic or monotropic E) A pentahydrate has four molecules of water of hydration 20. Which of the following is an appropriate size range for the particles/droplets of a pulmonary aerosol? A) 0-1 micrometres B) 1-5 micrometres C) micrometres D) 3-5 centimetres E) 1-5 nanometres 21. Which of the following pieces of equipment is used for the determination of aerodynamic diameters for a pulmonary aerosol? A) A stack of powder sieves B) A differential scanning calorimeter C) An Anderson cascade impactor D) A light microscope E) A metre rule 22. Which of the following is a valid reason why protein drugs cannot be delivered using an ultrasonic nebulizer? A) The protein molecule is too big to be incorporated into an aerosol droplet B) The protein must be provided as a sterile solution C) Proteins are not absorbed from the airways D) The protein may be denatured by heat generated during nebulisation E) Ultrasonic nebulisers are very expensive

7 7 23. Which of the following statements is TRUE considering softgel capsules? A) Glycerol can be used as a plasticiser in softgel capsule shells B) The capsule shell formation and capsule filling are two separate processes C) The capsules are produced by pressing the gelatin film onto cold moulds D) Softgel capsules are mostly used for controlled drug release E) The capsules are composed of high bloom strength gelatin 24. Which of the following statements is TRUE concerning bottle packs? A) All types of pharmacopoeial glasses can be used for parenteral formulation packaging B) PVC is commonly used as the main polymer in plastic bottles C) Neutral glass has a low hydrolytic resistance D) HDPE shows a lower vapour permeation than glass E) Plastic bottles may have leakage of plastic additives 25. Which of the following statements is FALSE concerning blister packs? A) The cavities of plastic blisters are made using pressurised plates B) PVC blisters are typically m thick C) Aluminium blisters have excellent barrier properties D) Aclar is more expensive than PVdC E) Cold-formed aluminium blister packs are commonly triplex 26. Which of the following statements is TRUE concerning packaging design and labelling? A) The batch number is not required on the packaging B) Legal statue of POM refers to pharmacy only medicine C) The strength of the medicine is preferable, but not necessary to be included on the packaging D) The labelling must all be in English E) There is no official regulation of medicine labelling TURN OVER

8 8 27. Which of the following statements is TRUE concerning dissolution and disintegration testing? A) The BP specification for the dissolution of drug from an immediate-release tablet is that more than 80% must be released within 15 minutes in 0.1 M HCl B) The BP method for dissolution testing can be used for in vivo drug absorption prediction C) The BP specification for the disintegration time of enteric-coated capsules requires that they remain intact in 0.1 M HCl for 2 hours and disintegrate in phosphate buffer ph 6.8 within 15 minutes D) The official disintegration test is performed at 25 C E) The BP method for dissolution testing uses 900 ml of ph 6.8 phosphate buffer 28. Which of the following statements concerning oral controlled release formulations is FALSE? A) Controlled release formulations can improve patient compliance by reducing the dosing frequency B) Steadier drug plasma concentrations can be achieved in patients through using controlled release formulations C) Zero-order drug release is expected from osmosis-controlled release formulations D) Multi-particulate controlled release formulations often cause less GI irritation than comparable single unit tablet formulations E) Superporous hydrogels are often used for controlled release formulations that target the colon 29. Which of the following statements concerning chrono-therapy is TRUE? A) Most chrono-therapeutic delivery systems are gastro-retentive formulations B) The time delay between dosing and drug release should be as long as possible C) Chrono-therapeutic delivery systems are mostly used for treating chronic diseases D) Chrono-therapy involves matching drug release with natural daily biological rhythms E) Chrono-therapeutic delivery systems can help relieve symptoms experienced by patients during their sleep

9 9 30. Which of the following statements in relation to drug delivery to the colon is TRUE? A) The ph of gastro intestinal fluid in the colon is the same as that in the small intestine B) Polymers containing azo bonds can be degraded in the colon by oxidation C) The likelihood of drugs reaching the proximal colon following rectal administration is high. D) Drug absorption in this region of the gut is negligible E) Eudragit polymers are often used as film coating materials in colon targeting drug delivery formulations END OF PART ONE TURN OVER

10 10 Part TWO 31. Answer ALL parts: (a), (b) and (c). Recently a new controlled release formulation platform, Egalet erodible tablets, has been developed. It is an erosion-based controlled delivery system and the design of the formulation is shown below. A drug is dispersed in the matrix and the release is controlled by the rate of erosion at the two ends of tablets. a) Describe in detail how erosion-based controlled-release systems act to control the release of drug from the formulation. [20%] b) Egalet erodible tablets can achieve zero-order drug release. Explain what zero-order drug release is and why it is desirable for controlled drug release formulations. [30%] c) Compare and contrast the use of erosion-based systems and membranelimited controlled-release tablet formulations. Include in your answer the advantages and disadvantages of each system. [50%]

11 Answer ALL parts: (a), (b) and (c). You are assessing the stability of a new drug XL388, which your company intends to market in an aqueous solution formulation. Chemically, XL388 is an amide. a) You are first asked to test the stability of the drug by heating it in buffer solutions with various ph values. Explain the rationale of using various buffers and an elevated temperature with reference to the most likely chemical process involved in the degradation. [20%] b) You find that XL388 is most stable at ph=4.9. When heating the buffered drug solution at 85 C, you observe the following degradation profile: Time (days) Drug concentration (% w/v) What reaction order do you expect for this type of decomposition? Plot the appropriate linear graph to confirm this order of reaction. Determine the reaction rate constant (k) from the graph. c) Further testing of the same solution shows that the rate constant at various temperatures is: Test temperature ( C) k (1/days) use your result from part b [30%] At least 95% of the drug content must remain intact upon storage of the solution at 25 C for a month. Using an appropriate graphical analysis, calculate the rate constant at 25 C and calculate the amount of drug remaining after 30 days at this temperature. Show ALL your working. [50%] TURN OVER

12 Answer ALL parts: (a), (b), (c) and (d). You are a formulation scientist. A proposed new dry powder inhalation product for insulin is in development in your company. The target pulmonary (respirable) dose is 18 mg. Your technician has run some samples of the prototype loaded with insulin through the Andersen cascade impacter at 28 L/minute to assess the drug delivery. Material landing on each stage has been collected and assayed. Stage Stage cut off (µm) Quantity on each stage Throat Fliter (a) Discuss the advantages and disadvantages of using a pulmonary aerosol to deliver a therapeutic protein from the airways into the blood. [20%] (b) Describe all methods for measuring aerosol particle size. [20%] (c) Explain the term MMAD and calculate the MMAD for this product. [20%] (d) Calculate the percentage of insulin which is respirable and comment on whether this device provides the correct dose of insulin? [40%]

13 Answer ALL parts: (a), (b), (c) and (d). You are a formulation scientist with responsibility for the development of solid dosage forms. Recently you have been developing a new hard gelatine capsule formulation for Drug X with an intended strength of the drug being 20 mg. The formulation contains crystalline Drug X. You find that a new batch of capsules (Batch B) appears to have a very different dissolution rate and content uniformity from a previous batch (Batch A). Table 1. Content uniformity (mg) data Batch A 24.0, 20.5, 18.9, 18.7, 21.3, 22.3, 20.5, 25.3, 21.6, 14.5 Batch B 20.2, 21.0, 20.8, 20.5, 21.6, 19.7, 19.5, 20.4, 21.5, 19.2 a) Briefly explain when hard gelatine capsules should be considered over conventional tablet formulations. [20%] b) Explain why differences in drug dissolution may be a significant problem. [20%] c) You have received some physical characterisation data of the two batches of crystalline drug X used for the Batch A and Batch B capsules. The differential scanning calormetery (DSC) results of the two batches of crystalline drugs are shown below. Describe what you think may be the cause of the change in the dissolution of Batch B. [20%] d) Briefly describe the BP method for measuring the content uniformity of capsule product. Comment on whether the two batches meet the BP specification for capsules content uniformity. Explain the possible reasons that may cause the observed difference in the content uniformity. [40%] END OF PAPER