Advanced Formulations Flashcards
Time for action IV
30-60 seconds
Time for action sublingual
3-5 minutes
IM
10-20 minutes
Rectal
5-30 minutes
Oral
immediate to extended
GTN Sublingual tablets vs spray
tablet can be spat out when vasodilation has occurred
counselling GTN
patient should sit down
spray under tongue, wait 5 mins
if symptoms haven’t relieved administer again
if same after 5 mins call ambulance
Advantages of:
- Oral
- IV
- Easy-to-use, Extended formulation available
2. 100% bioavailability, fast onset
Advantages of
- Topical
- Pulmonary
- easy, non-invasive
4. rapid absorption, inhaled with low systemic absorption
Barriers to oral drug delivery
GIT - pH, enzyme degradation, binding
Mucus - diffusion, binding, electrostatic repulsion
Membrane transport - diffusion, recognition, enzymes - brush border
Liver - 1st pass
Routes of absorption across epithelia
Paracellular - between cells
Transcellular - through cells (passive, carrier-mediated, endocytosis)
EFFLUX (P-gp)
Transcellular carrier-mediated
Large neutral amino acid carrier system
requires energy
against gradient
may require associated ions H+ Na+
Transcytosis comparion of types
Receptor-mediated - specific, saturable
Adsorptive endocytosis - non-specific, unsaturable
Mechanism of enteric coating
e.g. SI, use polymer insoluble pH<4 but soluble above. Use plasticiser to avoid the coat cracking
Colon-specific release strategies (3)
- enzyme triggered - polymers or prodrugs
- pH controlled - polymers using above 7 as the trigger
- time-controlled - polymers
Sustained release systems (4)
Bio-erosion
Gastro-retentive - floating, swelling+expandable
Diffusion - reservoir, matrix
Dissolution - increase particle size, use slow dissolving matrix, tablet coating
Disadvantages
- Oral
- Rectal
- unsuitable - vomiting, difficulty swallowing
slow, unpredictable absorption
hard to mask taste - Patient acceptability
Disadvantages
- SC or IM
- IV
3.Unpredictable absorption, sore
4. requires functioning cannula, can be distressing
local infection, reaction
Disadvantages:
- topical - desired MW log P
- Inhaled
- MW<500 moderate log P 1-4 desired
slow absorption - Inhaler technique
size of drug particles delivered
Onset of action of GTN formulations
Spray>tablets>Parenteral injection>Patches and ointment
SL tablets - description of administration, advantages and disadvantages
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.
Buccal absorption of basic drugs change according to increase of pH of their solutions
Buccal absorption of basic drugs increases with increasing pH of their solutions
Are weakly acidic or weakly basic drugs absorbed when the pH is well below pKa?
Weakly acidic
IM and SC administration,
muscle tissue
oily vehicles
lower MW + dispersion rate
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
Compare advantages/disadvantages of MDI with DPI
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
Regarding the physiology of the respiratory tract, which of the following statements are true?
- The diameters of the conducting airways decreases towards the alveoli
- Drug absorption from the respiratory tract occurs at the alveoli
- The surface area of the alveoli is > 100 meters squared.
- The primary mechanism of elimination of particles > 5 um is expiration.
1 and 2
Concerning the formulation and use of MDI, which of the following statements are true?
- Oxidation of drugs is minimised.
- MDI are usually formulated to ensure that the drug is soluble within the propellant system.
- MDI require the inclusion of a preservative
- MDI may be easily formulated to contain water
1
Concerning the formulation of DPI, which of the following are true?
- Liquid propellants are not required.
- The Mass Median Aerodynamic diameter of the therapeutic agents should be < 5 um
- Lactose is commonly used to improve the flow properties of the powdered drug
- Following inspiration, both lactose and the powdered drug reach the site of action.
1,2,3
True statements regarding MDI:
- Administration of high doses of therapeutic agent
- Convenience for the patient
- Requirement for patient’s ability to co-ordinate actuation and inhalation
- Greater efficiency than nebulisers.
2,3,4
Advantages/disadvantages of colon-specific drug strategies?
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
Advantages of tablets
- 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)
In relation to buccal and SL formulation which statements are true:
- Drugs absorbed by these routes bypass the liver
- absorption through the buccal epithelium is not affected by the partition coefficient of the drug
- buccal absorption of basic drugs increases with increasing pH of their solutions
- buccal absorption of acidic drugs increases with increasing pH of their solutions
- there is an optimum log P for SL absorption
1,3,5
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
A,D,E
IV and tumour targeting strategies
nanoparticles. Cancer drugs typically need to reach cancer but can damage normal healthy cells producing undesired side effects
e. g. doxorubicin - liposome
liposomes
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
What are liposomes?
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.
timed colon release mechanism
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
