Transdermal, suppositories and aerosol Flashcards
What are some advantages to transdermal patch drug delivery
- Provide controlled continuous drug input over long periods
- Readily terminated
- Readily identifiable in emergencies
- Readily accessible site of administration
- Avoid variables that influence GI absorption
- Avoid first pass metabolism
What are some barriers limiting percutaneous drug absorption
Stratum corneum - lipophilic layer, no water
Appendages
Viable epidermis
Dermis
CirculationB
What are some biological barriers
Binding to receptors
Partitioning into and retention by fat droplets
Metabolism by enzymes
What are ideal properties of drug transdermal delivery
Low mw
* <500 Da
Relatively lipophilic
* Log P 2
o Needs to go thorugh lipophilic membrane
Low mp
* <150C
Sufficient solubility in water at pH 6-7.4 to deliver required dose
* pH of the skin
Suitable pKa
* Unionised at physiological pH
High potency
* 1mg/cm/day
What are the design principles of transdermal patches
Suitable drug molecule
For immediate and sustained drug release
Apply strong driving force for drug to leave transdermal patch
* Saturate drug concentration to achieve maximum concentration gradient across skins
* Suspension of drug solids in vehicle to achieve sustained release
Apply co-solvents to modify skin permeability and drug solubility
Apply impermeable barrier to ensure occlusion - retard water loss to enhance skin hydration and permeability
Explain Ficks Law
- Increase Cs by using appropriate excipients
- Maintain Cs by suspending solid drug particles in system
o Ensure constant drug release
o Requires insoluble drug particles to ensure that concentration of Cs maintains high for diffusion - Diffusion force = difference in concentration from high to low
What is the difference between matrix and membrane system for TDDS
What are the five layers of TDDS
Backing layer of tan-coloured, aluminized polyester film
Drug reservoir of scopolamine, light mineral oil and polyisobutylene
Microporous polypropylene membrane to control rate of drug delivery
Adhesive layer with scopolamine priming dose
Protective peel strip to be removed before use
Provide some counselling points for TDDS
Quality standards and compendial requirements for TDDS
Explain the rectal formulation - local action, systemic action and diagnostic action
Formulation:
Enemas - solutions, suspensions and emulsions
Rectal capsules
Rectal creams, ointments and foams
Rectal suppositories
Local action:
Treatment of pain and itch due to haemorrhoids, antiseptics and laxatives
Systemic action:
Anti-asthmatics
Anti-inflammatory
Analgesics
Diagnostic action:
Barium enema
Explain the vaginal formulation - local action, systemic action and special consideration
Formulation:
Solutions
Sprays and foams
Tablets and capsules
Creams and ointments
Pessaries
Local action:
Antifungal, lubricants and antibacterial agents
Systemic action:
Hormonal imbalance - progesterone and oestrogens
For contraception
Special considerations:
Low moisture content in vagina under normal physiological conditions
Vaginal microflora
Irritation
Leakage - stain clothing, fatty base not preferred
Suppository base requirements
Melt or dissolve in physiological fluids
Exhibit adequate volume contraction after solidification to enable easy removal in manufacture
Optimised viscosity on melting
* Pourable into the mould
Chemical and physical stability
Compatible with drug
Permit optimal drug release
Advantages and disadvantages of coca butter
Advantages
* Nontoxic and non-irritating
* Compatible with many drugs
* Melts too quickly at body temperature
Disadvantage
* Natural product - variable composition
* Low softening temperature, further lowered by drug incorporation
* Exhibit polymorphism beyond 35C
o Metastable states mp 18-28C
* Poor water absorption
Advantages and disadvantages of synthetic triglyceride bases
More widely used than theobroma
* Available with different mp to accommodate drugs that lower melting point of bases
* More stable and don’t exhibit polymorphism
* Properties can be modulated
o Add glycerol monostearate to improve water sorption
o Add tween 80 to reduce tendency to fracture
What are some water soluble/ miscible bases
Glycerin gelatin
Macrogols
Very high osmotic effects = laxatives
Disadvantages of water soluble/ miscible bases
- Hygroscopic
- Preservatives required
- Require moistening with water to reduce pain on insertion
- Slow dissolution in rectum
- PEGs incompatible with some drugs and containers
Quality and compendial requirements for suppository
Appearance = smooth, uniform texture and appearance - colour and odour
Disintegration - Fat-based = 30mins, Water soluble base = 60mins
Uniformity of dosage units -
weight variation >25mg and >25% of total mass
content uniformity if drug if <25mg or 25% of total mass
What are some advantages of aerosol formulations
Withdrawal of one portion does not contaminate or exposure remaining dosage form
Hermetic seal and opaque packaging
* Protection against oxygen, moisture, light and microbes
Dosage characteristics are preserved
Accurate dosing by metered valves
Can be applied without touching lesion - reduce irritaion and mechanical damage to lesions
Clean application
Wat are the applications of aerosols
Nasal/ pulmonary delivery
Topical delivery
Rectal/ vaginal delivery
What is the two phase system of aerosols
One liquid phase with liquefied propellants and drug formulation
Vapour phase - propellant
What is the three phase system of aerosols
Two liquid phase with liquefied propellant and aqueous drug formulation
Vapour phase - propellant
What is the compressed gas system
One liquid phase comprising drug formulation
Vapour phase - compressed inert gas - N2, CO2, N2O
What are propellants
Comprise of gas that has been liquefied under high pressure below critical temperature in the canister
* When expelled it expands and vaporises to deliver drug formulation as a fine mist
HFA-134a
HFA-227
What are dermatological aerosols used for
For solutions, emulsions, suspensions, powders and semisolids
Application of drugs to burns and open wounds
* Steroids
* Antibiotics
* Astringents
What are rectal and vaginal aerosols used for
Delivery of estrogens, anti-inflammatory agents and drugs for contraception
Delivered as foams
Nasal aerosols and sprays
Solutions or suspension formulations
Local or systemic action
What are examples of pulmonary aerosols
MDI or pMDI
Dry powder inhalers
Nebilisers
What are advantages and disavantages of MDI or pMDI
Advantages
* Portable and effective aerosol generator
* Low cost per dose
* Reproducible multidose delivery
* Canister protects against oxidative degradation and bacterial contamination
Disadvantages
* Drug BA is highly dependent on correct use by patients
* Inefficient drug delivery
What are advantages and disavantages of dry powder inhalers
Advantages
* Breadth actuated
* Spacer not necessary
* Portable
Disadvantages
* Adequate inspiratory flow required
* May result in high pharyngeal deposition
* Drug delivery potentially affected by humidity
What are nebulisers
Devices that transform drug solutions/ suspensions into aerosols
* Use mouthpiece or mask to deliver dose
Advantages and disadvantes of spacers
Advantages
Enhance drug delivery - extend mouthpiece, direct drug spray towards mouth to reduce drug loss into air
Compensate for poor patient technique/ coordination
Reduce oropharyngeal drug deposition
* Smaller particles as they travel along spacer
Disadvantages
Bulky size
Regular cleaning to minimise bacterial contamination
Electrostatic charges reduce drug delivery
What are aerodynamic equivalent diameter
Diameter of an equivalent sphere of unit density that has an identical settling velocity as the particle
* Equivalent to spherical drop of water with identical settling velosity
* Dependent on particle diameter, shape and density
* Determines site of deposition
What are MMAD and GSD
Mass median aerodynamic diameter (MMAD) - d50%
* AED at which 50% of particles are larger and 50% are smaller
Geometric standard deviation (GSD) - spread of particle size
Respirable dose and fraction
Inhalable fraction
* MMAD <100micron
Thoracic fraction
* MMAD 11.64micron
* GSD 1.5 micron
Respirable fraction
* MMAD 4.25micron
* GSD 1.5micron
What are compendial requirements for aerosols
Dose or spray content uniformity throughout container life - mass per sungle dose
Droplet and drug particle size distribution
Spray pattern
Plume geometry
Priming and repriming - initial use and >24hrs or 7days
Tail off profile
