Advanced Formulations

Question 1

Time for action IV

Answer 1

30-60 seconds

Question 2

Time for action sublingual

Answer 2

3-5 minutes

Question 3

IM

Answer 3

10-20 minutes

Question 4

Rectal

Answer 4

5-30 minutes

Question 5

Oral

Answer 5

immediate to extended

Question 6

GTN Sublingual tablets vs spray

Answer 6

tablet can be spat out when vasodilation has occurred

Question 7

counselling GTN

Answer 7

patient should sit down
spray under tongue, wait 5 mins
if symptoms haven’t relieved administer again
if same after 5 mins call ambulance

Question 8

Advantages of:

1. Oral
2. IV

Answer 8

1. Easy-to-use, Extended formulation available

2. 100% bioavailability, fast onset

Question 9

Advantages of

3. Topical
4. Pulmonary

Answer 9

3. easy, non-invasive

4. rapid absorption, inhaled with low systemic absorption

Question 10

Barriers to oral drug delivery

Answer 10

GIT - pH, enzyme degradation, binding
Mucus - diffusion, binding, electrostatic repulsion
Membrane transport - diffusion, recognition, enzymes - brush border
Liver - 1st pass

Question 11

Routes of absorption across epithelia

Answer 11

Paracellular - between cells
Transcellular - through cells (passive, carrier-mediated, endocytosis)
EFFLUX (P-gp)

Question 12

Transcellular carrier-mediated

Answer 12

Large neutral amino acid carrier system
requires energy
against gradient
may require associated ions H+ Na+

Question 13

Transcytosis comparion of types

Answer 13

Receptor-mediated - specific, saturable

Adsorptive endocytosis - non-specific, unsaturable

Question 14

Mechanism of enteric coating

Answer 14

e.g. SI, use polymer insoluble pH<4 but soluble above. Use plasticiser to avoid the coat cracking

Question 15

Colon-specific release strategies (3)

Answer 15

1. enzyme triggered - polymers or prodrugs
2. pH controlled - polymers using above 7 as the trigger
3. time-controlled - polymers

Question 16

Sustained release systems (4)

Answer 16

Bio-erosion
Gastro-retentive - floating, swelling+expandable
Diffusion - reservoir, matrix
Dissolution - increase particle size, use slow dissolving matrix, tablet coating

Question 17

Disadvantages

1. Oral
2. Rectal

Answer 17

1. unsuitable - vomiting, difficulty swallowing
   slow, unpredictable absorption
   hard to mask taste
2. Patient acceptability

Question 18

Disadvantages

3. SC or IM
4. IV

Answer 18

3.Unpredictable absorption, sore
4. requires functioning cannula, can be distressing
local infection, reaction

Question 19

Disadvantages:

5. topical - desired MW log P
6. Inhaled

Answer 19

5. MW<500 moderate log P 1-4 desired
   slow absorption
6. Inhaler technique
   size of drug particles delivered

Question 20

Onset of action of GTN formulations

Answer 20

Spray>tablets>Parenteral injection>Patches and ointment

Question 21

SL tablets - description of administration, advantages and disadvantages

Answer 21

Formulation: Held within the oral cavity, below the tongue and slowly dissolve. Designed to dissolve slowly and not disintegrate.
Advantages; Give rapid absorption into the systemic circulation. Avoids first pass metabolism.
Disadvantages; issues with eating, drinking or smoking, as can affect how the drug is absorbed and how well it works.

Question 22

Buccal absorption of basic drugs change according to increase of pH of their solutions

Answer 22

Buccal absorption of basic drugs increases with increasing pH of their solutions

Question 23

Are weakly acidic or weakly basic drugs absorbed when the pH is well below pKa?

Answer 23

Weakly acidic

Question 24

IM and SC administration,
muscle tissue
oily vehicles
lower MW + dispersion rate

Answer 24

Muscle tissue is more acidic than normal physiological fluids
Oily vehicles may be used to provide diffusion over a prolonged period
Dispersion of soluble drugs from the injection site is more rapid the lower the molecular weight of the drug

Question 25

Compare advantages/disadvantages of MDI with DPI

Answer 25

Both particle size <5um MDI - cheaper, hermetically sealed reducing contamination. Stability issues, need co-ordination. DPI - less co-ordination, no propellant, less irritation. Require excipients, cannot be used with spacer

Question 26

Regarding the physiology of the respiratory tract, which of the following statements are true? 1. The diameters of the conducting airways decreases towards the alveoli 2. Drug absorption from the respiratory tract occurs at the alveoli 3. The surface area of the alveoli is > 100 meters squared. 4. The primary mechanism of elimination of particles > 5 um is expiration.

Answer 26

1 and 2

Question 27

Concerning the formulation and use of MDI, which of the following statements are true? 1. Oxidation of drugs is minimised. 2. MDI are usually formulated to ensure that the drug is soluble within the propellant system. 3. MDI require the inclusion of a preservative 4. MDI may be easily formulated to contain water

Answer 27

1

Question 28

Concerning the formulation of DPI, which of the following are true? 1. Liquid propellants are not required. 2. The Mass Median Aerodynamic diameter of the therapeutic agents should be < 5 um 3. Lactose is commonly used to improve the flow properties of the powdered drug 4. Following inspiration, both lactose and the powdered drug reach the site of action.

Answer 28

1,2,3

Question 29

True statements regarding MDI: 1. Administration of high doses of therapeutic agent 2. Convenience for the patient 3. Requirement for patient’s ability to co-ordinate actuation and inhalation 4. Greater efficiency than nebulisers.

Answer 29

2,3,4

Question 30

Advantages/disadvantages of colon-specific drug strategies?

Answer 30

Advantages: avoid enzyme degradation in the low pH of the stomach and SI Disadvantages: - drug still subject to 1st pass -concentration of microorganisms in the colon is very high and little is known about the possibility of pre-systemic drug metabolism by these molecules

Question 31

Advantages of tablets

Answer 31

- can contain multiple APIs - accurate dose - easy, convenient - control where drug is released - offer taste masking to a degree - generally most stable format for an API (water accelerates the breakdown)

Question 32

In relation to buccal and SL formulation which statements are true: 1. Drugs absorbed by these routes bypass the liver 2. absorption through the buccal epithelium is not affected by the partition coefficient of the drug 3. buccal absorption of basic drugs increases with increasing pH of their solutions 4. buccal absorption of acidic drugs increases with increasing pH of their solutions 5. there is an optimum log P for SL absorption

Answer 32

1,3,5

Question 33

In relation to absorption of drugs from i.m. and s.c. injections, which of the following statements are correct? a) Dispersion of soluble drugs from the injection site is more rapid the lower the molecular weight of the drug b) Binding to muscle protein increase the rate of absorption c) Hydrophilic drugs bind strongly to muscle protein d) Muscle tissue is more acidic than normal physiological fluids e) Oily vehicles may be used to provide diffusion over a prolonged period

Answer 33

A,D,E

Question 34

IV and tumour targeting strategies

Answer 34

nanoparticles. Cancer drugs typically need to reach cancer but can damage normal healthy cells producing undesired side effects e. g. doxorubicin - liposome

Question 35

liposomes

Answer 35

IV into bloodstream where they accumulate at tumour (leakier blood vessels). Increases solubility, stability. Silicone degrades releasing doxorubicin at site of action. Favourable biodistribution, pKa, safety profile. These molecules spontaneously formed nanoparticles which were taken up by tumour

Question 36

What are liposomes?

Answer 36

A liposome is a spherical-shaped vesicle that is composed of one or more phospholipid bilayers, which closely resembles the structure of cell membranes. The ability of liposomes to encapsulate hydrophilic or lipophilic drugs have allowed these vesicles to become useful drug delivery systems.

Question 37

timed colon release mechanism

Answer 37

The drug is incorporated into pellets. These are coated with slow-release polymer then a second coat is applied. This is then compressed into a tablet