• A research and development department in a large multinational biopharmaceutical company is looking to develop an oral anti-cancer medicine. The initial hit compound has shown over 90% protein binding efficiency, high membrane permeability but very low solubility (BCS II compound). To enhance the bioavailability of the compound, the company has decided to utilise an amorphous solid dispersion formulation strategy.

 

(i) What are amorphous and amorphous solid dispersions?

[20%]

 

(ii) What are the advantages of this amorphous solid dispersion strategy?

[30%]

 

 

 

• Immunogenicity is a significant problem within protein therapeutics. Discuss thoroughly why such immunogenic reactions occur.

[50%]

 

Please write your answer between the lines above and below this sentence (you may delete this text)

 

• In 1975, Chien et al. published a research article entitled ‘Controlled Drug Release from Polymeric Delivery Devices III: In Vitro-In Vivo Correlation for Intravaginal Release of Ethynodiol Diacetate from Silicone Devices in Rabbits’. In that study, female rabbits (n=40) were implanted with silicone vaginal rings containing ethynodiol diacetate for up to 8 In an effort to establish an in vitro–in vivo correlation, Chien and his co-authors produced the following graph, showing the correlation between the plasma concentration (C_B) of norethindrone (the major metabolite of ethynodiol diacetate) and the in vitro release rate (Q/t; referred to as ‘flux’ in the figure caption) at various time points.

 

 

Figure 1.

 

 

1. What level of in vitro–in vivo correlation (IVIVC) do the data in the figure represent? Give a reason for your answer.

[10%]

 

1. Across how many time points were the in vivo and in vitro data collected?

[10%]

 

The article also includes the following graph, showing in vitro cumulative drug release (Q) versus the square root of time for a silicone elastomer ring device initially containing 30 mg ethynodiol diacetate.

 

 

 

• Based on the data presented in this in vitro release graph, comment on the type (i.e., the design) of the vaginal ring that was tested.

[20%]

 

1. How might you change the formulation to increase the rate of release of ethynodiol diacetate?

[10%]

 

 

• With reference to a specific example you have studied, outline the experimental techniques that can be used to investigate microbial penetration across microneedle-punctured skin.

[50%]

 

Please write your answer between the lines above and below this sentence (you may delete this text)

 

 

Naproxen is a popular nonsteroidal anti-inflammatory drug (NSAID) that is a widely used oral dosage form for mild-to-moderate pain. The chemical structure of naproxen is shown in Figure 1 (pKa = 4.15).

 

Figure 1 Chemical structure of naproxen.

• What is the % ionisation of naproxen at pH=5?

[20%]

 

• According to the Merck Index, naproxen has a solubility of 0.0159 mg/mL in water and good membrane permeability. The maximum dose of naproxen for adult patients is 500mg (tablet) twice per day. Based on the given information, which BCS class is naproxen? Clearly explain your reasoning.

[20%]

 

• Naproxen sodium is a modification of naproxen with greater water solubility at 250 gram/L. Please explain the reason behind the increase in water solubility for naproxen sodium. Also explain how the increased solubility of naproxen sodium would affect the bioavailability of the drug.

[20%]

• Company A is trying to produce a generic product for naproxen sodium using a wet granulation process. Please explain the potential process-induced phase transformations that can occur and the methods used to characterise them.

[40%]

 

Please write your answer between the lines above and below this sentence (you may delete this text)

 

 

 

(a)        Describe the differences between top-down and bottom-up approaches in liposome production, including an example of each approach.

[30%]

(b)        Discuss the advantages non-viral vectors have over viral vectors for nucleic acid delivery.

[30%]

(c)         Discuss the composition, structure, and nucleic acid release mechanism of the Pfizer BioNTech vaccine for COVID 19 that have led to the positive immune response in humans.

 

 

 

The thermoresponsive polymer poly(N-Isopropylacrylamide) (PNIPAAm) has properties that make it useful for drug delivery.

(a) Fully explain how the thermoresponsive properties of this polymer enable in-situ implant formation.

[75%]

(b)    List FIVE factors that can alter its lower critical solution temperature (LCST).

[25%]

 

 

Q1.  Tablets are often coated using a film coating process. Discuss the reasons why film coatings may be applied to tablets.

[100%]

 

 

 

PMY8111 Section A Question 3 PMY8111 Section B Question 2 PMY8111 Section A Question 2 PMY8111 Section B Question 1 PMY8111 Section A Question 4 PMY8111 Section A Question 1

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