Summarise buccal and sublingual administration and factors affecting it.
Drug is places under the tongue or retained in the mouth.
- provides systemic admin avoiding exposure to GI tract and liver
- area well perfused with blood
- oral mucosa acts as barrier and is not highly permeable
- most subtances absorbed by passive diffusion
Partition coefficient (logP) important - if larger than 3.3, compound is more water soluble.
What are advantages (10) and disadvantages (5) of buccal admin?
Advantages:
- Avoids first pass effect
- Abundance of blood vessels
- Less hostile environment than GIT
- Ease of admin and termination
- Fast cellular recovery
- Directly and easily modified microenvironment
- Lower intersubject varability compared to transdermal patches
- Good for drugs that are extensively metabolised in liver or unstable in the GIT
- Major barrier (stratum corneum) is absent in comparison to transdermal patches
- Sustained release is achieved
Disadvantages:
- Small absorptive SA vs GIT
- Movement affects mucoadhesive systems
- Less permeable than the small intestine
- Salivation and swallowing
- Taste making of drug is required
What are the main applications of buccal admin?
Traditionally used for local conditions such as sore throat or local infection.
- suitable for delivery of large hydrophilic and unstable proteins, oligonucleotides and polysaccharides
What are charactersitics and functions of the nasal cavity?
For smelling, heating and humidifying air
- mucus layer is 5-20mm thick and is 2 layers
- SA is ~160cm^2
pH of mucus layer is 5.5-6.6, and of surface cells is 7.4 (physiological pH)
- back 2/3 of cavity is covered in cilia; mucociliary escalator
What is nasal delivery used for and what are the advantages?
For alleviation of nasal symptoms or an alternative to injections for drugs inactivated by GIT. Can also be used to deliver vaccines, peptides, insulin etc due to ability to cross the BBB.
Advantages of nasal delivery are:
- avoids first-pass metabolism
- rapid absorption, short exposure time fro enzymatic activity to occur
- low level of enzymes and is easily saturated with drug.
Describe an ideal drug candidate for nasal delivery.
- aqueous solubility in dose of 20mL per nostril
- appropriate absorption properties having no; offensive odours, irritants, toxic nasal metabolites and having suitable stability.
How can nasal absorption be enhanced?
- Increased absorption of drug
- Not cause permanent damage or alteration to the tissues
- Shouldnt be irritating or toxic to either the local area or rest of the body.
- Be effective in small quantities
- Enhancing effect should be temporary and reversible
- Enhancers should fulfill all other expectations of formulation excipients (stability and compatibility)
Describe IV admin
- immediate acess to blood stream and so 100% F
- max plasma conc can be reached rapidly (~4mins)
- Duration of action depends on: dose, timescale of admin, distribution, metabolism and excretion
- large or small volumes can be given
Describe IM admin of different drug types.
Administration to the muscular layer.
Hydrophilic neutral compounds;
Drug disperses from this site based on particle size.
Molecules diffuse through muscle fibres, pores of capillary walls (rate-limiting step) and into the blood stream.
Rate of movement is based on solubility of the drug and its precipitation in the local environment.
Injection of weak electrolytes;
- increases absorption with increased lipophilicity
- may bind to muscle protein.
Describe SC injection.
- Dissolution and absorption phases occur slower than in IM as blood supply is not the best
- Greater patient to patient variation in time to Cmax (due to amount of fat)
- Max dose approx 1mL
E.g. Insulin, adrenalin
Describe intrathecal admin
- Admin of drug in solutions by intrathecal catheter
- Opportunity to deliver drugs to brain and spinal cord
- More invasive than IV, IM or SC
- Implanted catheters and pumps have been used to reduce risk of injection on repeated puncture
What are advantages and disadvantages of rectal drug delivery?
Advantages
- When patient cannot used oral route (GI side effects, insufficient stability, pH)
- When drug is less suited to oral admin
- Avoidance of first pass
Disadvantages
- Aversion
- Slow and sometimes incomplete absorption
- Considerable inter and intra subject variation
Describe the anatomy and physiology of the rectum
- Rectum is part of the colon, being the last 150-200mm of the GIT
- Essentially hollow, relatively flat wall surface
- Rectal mucosa is a normal lipodial barrier, total SA is ~300cm^2
- Mucus volume ~3mL
- pH approx 7.5 - little buffering capacity
- Three seperate veins
- No esterase or peptide activity
- No active transport mechanisms
Describe absorption in the rectum
- Drug molecules enter general circulation directly or via liver
- Extent of avoidance of first pass is based on the site of absorption
- Depending on the vehicle, a suppository will either dissolve in rectal fluid or melt on the mucus layer
How is vaginal delivery used?
Generally for local effects
Can acheive systemic absorption
- Drug enters systemic and avoids first pass
- Wide network of blood vessels
E.g. Steroids, prostaglandins, some antibiotics
How does absorption occur in vaginal delivery? Describe anatomy.
- Epithelial layer increases in thickness after puberty an menopause
- SA increased by folds and ridges
- pH decreases after puberty, 4-5
- Little fluid in vagina
- Absorption tends to be variable
E.g. Pessaries and other dosage forms
Describe pulmonary delivery
- Generally used to treat prophylaxis or airway disease
- Rapid onset of activity for local action
- Useful where drug is poorly absorbed orally
- Large SA, abundance of capillaries
What are advantages and disadvantages of pulmonary delivery
Advantages
- Direct admin to site of action
- Smaller quantities of drug required
- Rapid onset of action
Disadvantages
- Seeking to defeat bodies natural defences
- Demands on patient (expensive)
- Deposition is technically inefficient (particles must be very small)
