9018

Semester 2, 2006

Page 1 of 15

THE UNIVERSITY OF SYDNEY Marks Per Q 1.5 9 90 Rec. Time 1.5 min each 9 mins each 90 minutes Marks Awarded SEAT NO ........................................................................ SURNAME .................................................................... OTHER NAMES. (Block letters)

Qs 1-30 31-35 Total

FACULTY OF PHARMACY BACHELOR OF PHARMACY DEGREE SECOND YEAR PHYSICAL PHARMACEUTICS AND FORMULATION A PHAR 2613 / PHAR2614 / PHAR 2616

Semester 2, 2006

TIME ALLOWED: 1.5 HOURS ANSWER ALL QUESTIONS

Electronic calculators may be used. The value of each question is indicated. Answers to questions 1-30 are to be indicated on the answer sheet provided. Answers to questions 31-35 must be written and calculations made within the space provided. ALL copies of this exam paper are to be returned to the examiner.

This examination booklet consists of 15 pages, numbered 1-15 inclusive. There are 35 questions, numbered 1-35 inclusive. Students are asked to check that their booklets are complete, and to indicate that they have done so by signing below. Students finding an incomplete booklet should obtain a replacement from the examination supervisor immediately. I have checked this booklet and affirm that it is complete. NAME SIGNATURE

9018

Semester 2, 2006

Page 2 of 15

SECTION A Questions 1-30 are worth 1.5 marks each. Recommended time: 1.5 minutes each.
QUESTION 1 Which ONE of these statements about Newtonian flow is INCORRECT? (A) (B) (C) (D) (E) Applied stress is directly proportional to shear rate The SI unit for viscosity is Pa.S The constant of proportionality is the viscosity Glycerol is a Newtonian liquid Viscosity varies with applied stress

QUESTION 2 Which ONE of these statements about non-Newtonian liquids is CORRECT? (A) (B) (C) (D) (E) Dilatant flow characteristics result from de-entanglement of long chain polymers under applied stress There is no yield stress in formulations which exhibit plastic flow Thixotropic fluids show a time dependent change in viscosity under a constant stress All pharmaceutical materials exhibit non-Newtonian behaviour Conventional creams will have dilatant flow

QUESTION 3 Which ONE of these statements about dilatant flow is INCORRECT? (A) (B) (C) (D) (E) Dilatant flow is most common in systems that contain a high concentration of solids Dilatant flow is the most common non-rheological property observed in molecular dispersion and semi-solid pharmaceutical formulations The viscosity of dilatant systems increases with increased sheer stress The granulation process, used in the preparation of tablet formulations, often show dilatant flow A hysterisis between applied and removed shear stress, with respect to flow, exists in dilatant systems

QUESTION 4 Which ONE of these statements is CORRECT? (A) (B) (C) (E) Osmosis is the free diffusion of solute and solvent molecules across a permeable membrane Osmotic pressure is influenced by the nature of the solute Osmotic pressure may be defined as the pressure required to resist the flow of molecules from the solvent to solute compartment. The addition of non-volatile solute to a solvent will result in an increase in vapour pressure

9018

Semester 2, 2006

Page 3 of 15

QUESTION 5 Which ONE of these statements is CORRECT? (A) (B) (C) (D) (E) Hypertonic solutions result in haemolysis Haemolysis is reversible Biocompatible isotonic solutions can be made by making a solution to 308 mOsmol There is no conceivable situation where you would need to prepare a hypertonic solution Large volume (infusions) should be hypertonic to reduce inflammation

QUESTION 6 Using sodium chloride equivalency, how much NaCl is needed to make a 2% adrenaline solution isotonic? (1% adrenaline HCl is equivalent to 0.29% NaCl) (A) (B) (C) (D) (E) 0.32%w/v 0.61% w/v 0.58%w/v 0.90% w/v 61%w/v

QUESTION 7 A novel osmotic pump tablet formulation is designed for the controlled release of an antiinflammatory agent. The release profile, along with experimentally recorded release data is shown below. Answer the following question:

Which ONE of these statements about the formulation is INCORRECT? (A) (B) (C) (D) (E) The rate constant is 2.5%.hr-1 The half life is 20 hours The shelf life is 2.5 hours The formulation follows first order release kinetics The release rate is constant

9018

Semester 2, 2006

Page 4 of 15

QUESTION 8 A conventional parenteral formulation degrades via first degradation kinetics. The rate constant for degradation in the fridge (4C) was calculated as 3 x 10-4 days-1. What is the shelf life at 4C? (A) (B) (C) (D) (E) 351 days 365 days 333 days 35 days 33 days

QUESTION 9 Which ONE of these statements about liquid formulations is CORRECT? (A) (B) (C) (D) (E) The saturated solubility is established when an equilibrium between the solution and excess solids is established Addition of a solvent to a saturated solution containing dispersed solids will result in dissolution Removal of solvent from saturated solution, containing dispersed solids, via evaporation will result in precipitation and crystal growth All of the above statements are correct None of the above statements are correct

QUESTION 10 Which ONE of the statements about solubility of non-volatile solids in liquids is CORRECT? (A) (B) (C) (D) (E) Increase in lattice energy in a crystal results in increased solubility The melting temperature of a drug molecule is independent of the crystal structure As the melting temperature increases the intrinsic solubility decreases All of the above statements are correct None of the above statements are correct

QUESTION 11 Which ONE of the following statements is CORRECT? As you reduce the particle size of a poorly water soluble drug from 100 m to 10 m: (A) (B) (C) (D) You increase the solubility by 10 times You increase the dissolution rate by 10 times Both A & B are correct Both A & B are incorrect

9018

Semester 2, 2006

Page 5 of 15

QUESTION 12 Which ONE of the following statements is CORRECT? One cannot increase the dissolution rate of the particles of a weakly acidic drug in water: (A) (B) (C) (D) By increasing the solubility of the drug By using the free acid form of the drug Both A & B are correct Both A & B are incorrect

QUESTION 13 Which ONE of the following statements about sink conditions is CORRECT? (A) (B) (C) (D) (E) Sink conditions do not affect drug dissolution Sink conditions rarely occur during the dissolution of drugs in the body (in vivo) Sink conditions refer to an order of magnitude difference in the saturated concentration of the drug and the concentration of the bulk solution All the above statements are correct Statements B & C are correct

QUESTION 14 Solubilisation of poorly water soluble drugs in liquid formulation is achieved using surfactants: (A) (B) (C) (D) (E) With a hydrophilic-lipophilic balance (HLB) value of 15 or bigger. At concentrations below the critical micelle concentration That are hydrophobic All of the above are correct None of the above statements are correct

QUESTION 15 A parenteral injectable preparation has to be: (A) (B) (C) (D) (E) Sterile, isotonic and pyrogen-free Non sterile and hypotonic Non sterile and hypertonic All of the above None of the above

QUESTION 16 If the solute concentration outside a cell is less than that inside of the cell: (A) (B) (C) (D) (E) The solution is hypertonic and crenation will result The solution is isotonic The solution is hypertonic and haemolysis will result. The solution is hypotonic and haemolysis will result. None of the above

9018

Semester 2, 2006

Page 6 of 15

QUESTION 17 Which ONE of these statements is INCORRECT? (A) (B) (C) (D) Ionic surfactants have a higher CMC than non-ionic surfactants Ionic surfactants form smaller micelles than non-ionic surfactants The attractive forces between the polar head groups of ionic surfactants result in the formation of micelles at lower surfactant concentrations As the hydrophobic chain length of an ionic surfactant increases the CMC decreases

QUESTION 18 The surface of a non steroidal anti-inflammatory tablet formulation has a contact angle with respect to water of 120. Which ONE of these statements about the formulation is CORRECT? (A) (B) (C) (D) (E) The formulation is easily wetted and will dissolve rapidly in the GI tract The surface of the tablet is hydrophilic A wetting agent will increase the contact angle between water and the tablet surface All of the above statements are correct None of the above statements above are correct

QUESTION 19 Which ONE of the following statements is CORRECT? (A) (B) (C) (D) (E) Micelles are formed when an amphiphile accumulates at the interface between oil and water An ionic surfactant is not an amphiphile A non-ionic surfactant is not an amphiphile Amphiphiles will not form an emulsion SDS is an amphiphile

QUESTION 20 Which ONE of these statements about the HLB system is CORRECT? (A) (B) (C) (D) (E) Surfactants with a high HLB will be predominately hydrophilic Surfactants with low HLB values will be soluble in non-polar solvents High HLB value surfactants (>15) solubilise compounds via micellisation All of the above statements are correct None of the above statements are correct

9018

Semester 2, 2006

Page 7 of 15

QUESTION 21 A series of n-alkyl cationic surfactants (n-alkyl - trimethyl ammonium bromide) were used to prepare aqueous non-polar drug formulations for nebulisation as an aerosol. Which ONE of the statements about the formulation is CORRECT? (A) (B) (C) (D) Increasing the chain length of the surfactant resulted in a reduced steroid solubility The CMC of the surfactant increased with increased alkyl chain length Improved solubility was achieved by accumulation of the drug in the lipophilic micelle core All of the above statements are correct

QUESTION 22 Which ONE of these statements about O/W emulsions is INCORRECT? (A) (B) (C) (D) (E) High concentrations of oil may result in phase inversion O/W emulsions are generally easier to prepare than W/O emulsions The water component acts as the dispersed phase O/W emulsions are most stable when the dispersed phase is 30-60% v/v O/W emulsions are more cosmetically acceptable than w/o emulsions

QUESTION 23 Which ONE of these statements about emulsions is CORRECT? (A) (B) (C) (D) (E) Addition of an ionic surfactant to an O/W emulsion may destabilise the formulation and result in cracking The process of cracking will result in a reduction in the net interfacial tension between the water and oil phase A cracked pharmaceutical emulsion is easily re-emusified by shaking. Commonly, only one emulgent is required for preparation of pharmaceutical formulations Emulsions are classified as suspended solids in an aqueous media

QUESTION 24 Which ONE of these statements about an O/W emulsion is INCORRECT? (A) (B) (C) (D) (E) Stokes equation may be used to predict the rate of creaming in an emulsion An increase in oil density will increase the rate of creaming Increasing the viscosity of the continuous phase will reduce the rate of creaming Reduction in the emulsion size will result in reduced creaming rates Stokes equation assumes a dilute dispersed phase

9018

Semester 2, 2006

Page 8 of 15

QUESTION 25 Which ONE of these statements about a particulate suspension is INCORRECT? (A) (B) (C) (D) (E) Stokes equation may be used to predict the rate of sedimentation in an emulsion An increase in particle density will increase the rate of sedimentation Increasing the viscosity of the suspending media will reduce the sedimentation rate Reducing the particle size will reduce the sedimentation rate Stokes equation takes into account particle-particle interactions

ANSWER THE NEXT 2 QUESTIONS BASED ON THE INFORMATION BELOW FOR A NEW ASTHAMA DRUG CHAN-ITROPIUM SULPHATE: Aerosol V X Y Z QUESTION 26 Which aerosol will least likely deposit in the lung? (A) (B) (C) (D) V X Y Z Particle diameter (m) 5 4 2 2 Inhalation flow (L/min) 120 15 60 15

QUESTION 27 Which aerosols will deposit to the same extent in the lung by the mechanism of inertial impaction? (A) (B) (C) (D) (E) V and X X and Y Y and Z X and Z None of the above

9018

Semester 2, 2006

Page 9 of 15

THE GRAPH SHOWS THE CHANGE IN SOLUBILITY OF DRUG X IN WATER WHEN ALCOHOL IS ADDED AS A CO-SOLVENT. ANSWER THE NEXT 2 QUESTIONS.

QUESTION 28 Which curve is correct if Drug X has a pKb of 4 and the solution pH is 7? (A) (B) (C) (D) I II III IV

QUESTION 29 Which curve is correct if Drug X has a pKb of 7 and the solution pH is 7? (A) (B) (C) (D) I II III IV

QUESTION 30 Which ONE of these statements about cream formulations is CORRECT? (A) (B) (C) (D) (E) Creams can be classified as structured emulsions Creams consist of oil, water, emulsifier and high molecular weight alcohol components A cream contains a lamella gel like structure to improve physical stability All of the above statements are correct All of the above statements are incorrect

SECTION B BEGINS ON THE NEXT PAGE

9018

Semester 2, 2006

Page 10 of 15

SECTION B Questions 31-35 are worth 9 marks each. Recommended time: 9 minutes each.
QUESTION 31 (9 MARKS)

A pharmacist inadvertently prepares an admixture of rapid-acting insulin with EDTA (a metal ion chelating agent). How would the stability of insulin be affected?

9018

Semester 2, 2006

Page 11 of 15

QUESTION 32

(9 MARKS)

A complexing agent is added to a drug solution at saturated concentration with excess drug present. The graph shows the relationship between the total drug concentration and the concentration of the complexing agent. Sketch on the graph and explain what would happen if one gram of drug is added at point B.

9018

Semester 2, 2006

Page 12 of 15

QUESTION 33

(9 MARKS)

You are required to formulate a non-soluble anti histamine suspension for the nasal treatment of seasonal allergy. Discuss (in terms of the various particulate forces) how the following formulation factors will affect the stability of this suspension: (i) Drug particle size (3 marks)

(ii) The addition of NaCl (3 marks)

(iii) The addition of surfactants (3 marks)

9018

Semester 2, 2006

Page 13 of 15

QUESTION 34

(9 MARKS)

You are required to prepare a stable 100ml O/W emulsion containing 10 ml beeswax (HLB 12) and 60 ml liquid paraffin (HLB 10) as the dispersed phase. You stabilize the formulation using 5 ml of emulgent system (Span 60 & Tween 80) (i) Calculate the quantities of Tween 80 (HLB 15) and Span 60 (HLB 4.7) required for this formulation. (6 marks)

(ii) List 3 types of emulsion instability and discuss in terms of the current formulation what would happen if you increased the concentration of dispersed phase. (3 marks)

9018

Semester 2, 2006

Page 14 of 15

QUESTION 35

(9 MARKS)

Discuss the likely rheological behaviour (in terms of flow and thixotropic behaviour) of the following formulations: (i) A dense suspension. (3 marks)

(ii)

A cream containing long molecular weight polymers. (3 marks)

(iii)

Saline infusion. (3 marks)

9018

Semester 2, 2006

Page 15 of 15

**** THIS IS THE END OF THE PAPER****

SPACE FOR ROUGH WORK