T1 L20:Hormonal Drug Delivery Flashcards
why do we have diff dosage forms (drug factors)
- Drug often in powder form
- Tiny doses of drug =mcg or mcg quantities
- Bulk up with excipients- such as water, lactose
why do we have different dosage forms for drugs (human factors)
- different clinical conditions have diff senses of urgency so diff routes - ie seizure or skin rash
- there are also diff types of patient ie babies, elderly
- diff routes of administration-subcutaneous routes- not broken down
- diff physicochemical properties of drug - particle size of drug and lipophilicity of drug molecule
what are the factors to consider when designing dosage forms
- Drug factors- solubility, partition coefficient, pKa, stability, MWt
- Biopharmaceutical factors - absorption, bioavailability, route of administration
- Therapeutic factors- disease, patient, route, local vs systemic delivery
what are the examples of routes of administration
- Transdermal
- Inhaled/pulmonary route
- ocular eye drops
-Rectal
what are the 4 diff types of hormones
- Modified amino acid derivatives- (derived from tyrosine) dopamine, thyroxine
- Peptide & proteins-(derived from amino acids) neuropeptides -vasopressin
- Steroids- (derived from cholesterol) sex hormones testosterone
- Eicosanoids - (derived from lipids) prostaglandins
describe what the 4 types of hormones are used for
1)Modified amino acid derivatives – generally orally active
2)Peptide and proteins -Susceptible to enzymatic degradation in GIT
Low absorption
3) Steroids - Susceptible to extensive first pass hepatic-orally active but has systemic effects
4) Eicosanoids
describe the area of a bioavailability graph
It describes how quickly the drug is being absorbed
look at slide 17 for oral doses
how did it go ?
For modified amino acid derivatives, what are the drug factors and biopharmaceutical factors as well as the therapeutic factors
drug factors- low dose required
biopharma- orally bioavailable
therapeutic- locally vs systemic
what are the excipients of a drug
if dose of a drug is small (25mcg) then you add subtances that is drug-inert:
- Diluents/fillers e.g. lactose, water
- Surfactants e.g. polysorbates
- Lubricants e.g. Mg stearate-manufacturing –less sticky
- Disintegrants e.g. starch
describe some characteristics of drugs that require local delivery
Site of administration = site of action
Rapid onset of action
Less drug required
Absorption into the blood stream is not required
Absorption into the blood stream can lead to unwanted side effects
give some examples of corticosteroids and what they are used to treat
Intra-articular injections – tennis elbow
Creams and ointments - eczema
Inhalers - asthma
Eye drops - inflammation
Suppositories - haemorrhoids
give the drug factors, biopharmaceutical factors and therapeutic factors of the hormone insulin
drug factors: peptide hormone
biopharma- not absorbed after oral admin
therapeutic factors- need systemic circ
aim to mimic insulin
how is insulin characterised
onset, peak, duration, route of delivery
describe long acting insulin analogs
Several long-acting insulin analogs are available to replace background, or basal, insulin needs. They provide relatively constant insulin levels that plateau for many hours after injection. These insulins are sometimes called “peakless” insulins. The two commercially available insulins are insulin detemir (Levemir®) and insulin glargine (Lantus®).
Detemir is injected once or twice a day.
Glargine is usually taken once daily, but may be given twice daily, if needed. There are always exceptions; consult with your provider for the best treatment plan for you.
It is important to take insulin detemir and glargine at the same time(s) every day to maintain the most predictable levels of basal insulin. Remember: These long-acting insulins can’t be mixed in the same syringe with other insulins – this could change how the insulin works.
describe rapid acting insulin
Rapid-acting insulins are used in insulin pumps, also known as continuous subcutaneous insulin infusion (CSII) devices. When delivered through a CSII pump, the rapid-acting insulins provide the basal insulin replacement, as well as the mealtime and high blood sugar correction insulin replacement.
what is the pulmonary route
Systemic delivery- Large surface area (80 – 140 m2) Thin epithelial barrier (0.1 – 0.2 mm) Good blood supply (100% cardiac output) Avoids harsh environment of GI tract Avoids first-pass hepatic metabolism
describe inhaled insulin
Rapid-acting inhaled insulin
Human insulin also is available in a powdered, aerosolized form that can be inhaled. Inhaled insulin is very rapidly absorbed from the lungs, and should be administered immediately before eating. It is used to cover mealtime bolus insulin requirements.
Although inhaled insulin is quickly absorbed, the action is quite prolonged (probably because the insulin in the airways is re-breathed), so there can be a risk of late-meal low blood sugars. Inhaled insulin alters the lung anatomy or structures, and changes the amount of air and the speed of the air passage in the lung. It is necessary to follow people’s lung or pulmonary function tests while on this kind of insulin replacement. Children, smokers and individuals with lung and certain medical problems shouldn’t use inhaled insulin.
what are the drug factors, biopharma an therapeutic factors
- steroid
- Variable absorption after oral administration
Extensive first pass hepatic metabolism, short t1/ - Systemic delivery required but try to avoid oral route
Either cyclical or continuous administration required
what are the alternative routes t increase bioavailability
parental
transdermal route
what can you offer for sustained release
Buccal route
vaginal-gel
describe IM injection
Oily injections – sustained release
Testosterone enantate (caster oil)
Testosterone decanoate, isocaprate, phenylproprionate and proprionate, proprionate, undecanoate
Implants – sustained release
Nexplanon (progestogen-only contraception)
what is the ester at position 17
Decreases water solubility Increases oil solubility Deactivates molecule Can’t bind to androgen receptor Ester cleaved/ hydrolysed in blood Restores –OH so can attach to receptor
describe the release of steroid molecule from oily depots of long-chain esters in muscle tissue
Oil has some affinity for water and thus allows penetration of water; the ester is hydrolysed at the surface of the droplet.
The total surface area of the droplet can influence release rate and hence pharmokinetics of the drug.
Droplet dimenions and total surface area influenced by:
force of injection
viscosity and surface tension of oil phase
size of needle
environment into which it’s injected – exercise can increase plasma levels by increasing surface area of droplet.
what does subdermal implant of Nexplanon do
progestogen only contraception
Contains etonorgestrel 68 mg in each flexible rod.
Delivered by sub dermal implantation
Provides effective contraception for up to 3 years unless BMI greater than 35 kg/m2 in which case may not provide effective contraception in 3rd year.
what are the different transdermal delivery routes of estradiol (systemic)
Patch Design and Technology
There are two major types of transdermal delivery system (TDS) products:
Reservoir — the active ingredient is held in a solution or suspension between the backing layer and a rate-controlling membrane.
Matrix — a solution or suspension dispersed within a polymer or cotton pad in direct contact with the skin and held to the skin by adhesive applied to the perimeter of the system .Drug-in-adhesive matrix is a refinement in which the polymer (in which the drug is dispersed) is an adhesive.
The container closure system for a TDS is usually a foil pouch made from multilaminates with foil, paper, and heat sealable polyethylene (PE) portions. The foil serves as a vapor barrier, and PE is used for heat sealing purposes.
what are the advantages of intranasal admin
Advantages
-Large surface area (~180 cm2)
-Highly vascularized
-Avoids first pass hepatic metabolism
-Good bioavailability for low MW compounds
what are the disadvantages to intranasal admin
Disadvantages
Mucociliary clearance
Metabolic activity
Poor bioavailability for high MW compounds
describe the buccal admin route
Mucoadhesive testosterone buccal delivery system Applied twice daily Adheres to gum or inner cheek Sustained release of testosterone through buccal mucosa
describe vaginal admin (systemic
Self-insertion and removal Continuous release Good patient compliance
describe vaginal admin local device
Vaginal ring (Estring) Estradiol released over 90 days
what is the intrauterine Intra-uterine progestogen-only device
Progestasert (Mirena) provides local rather than systemic contraception.
May inhibit sperm survival and/or alter uterine environment to prevent nidation.
Advantages
Uses natural hormone at much lower dose than by other routes.
Don’t need to take/admin daily
No estrogens
T-shaped device for comfort, safe
