L20 - Hormone drug delivery Flashcards
Types of hormones
Modified amino acid derivatives - dopamine, thyroxine
Peptide and proteins - insulin, vasopressin
steroids - testosterone, hydrocortisone
eicosanoids
prostaglandins and leukotrienes
When might you not want systemic delivery?
side effects
low bioavailability
Modified amino acid derivative factors
Drug factors - low dose required
biopharmaceutical factors - which route? - orally bioavailable
therapeutic factors: local vs systemic delivery
excipients for small dose like thyroxine 25 micrograms
what are excipients
An excipient is a substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts (thus often referred to as “bulking agents”, “fillers”, or “diluents”)
Types of excipients; diluents - lactose, water surfactants - polysorbates lubricants - mg stearate disintegrants - starch sweetening agents preservatives viscosity enhancing agents - cellulose derivatives
How can corticosteroids be delivered locally?
intra-articular injection - tennis elow creams - eczema inhalers - asthma eye drops - inflammation suppositories - haemorrhoids
Factors for peptide hormone INSULIN
drug factor: peptide hormone large molecule
biopharmaceutical factors - not absorbed after oral administration because of Enzymatic degradation in lumen of GIT
therapeutic factors - need systemic circulation
How are insulins characterisd?
differences in:
onset - how quick they act
peak - how quick they achieve max impact
duration - how long they act
route of delivery - subcutaneous, inhaled
What are long acting insulin analogs?
Long-acting injected insulin analog
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®).
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.
why is the pulmonary route good?
large surface area thin epithelial barrier good blood supply avoids harsh environment of GI tract avoids first pass hepatic metabolism
Sex hormones factors
drug factors - steroid lipophilic
Biopharmacetuical factors -variable absorption after oral administration
extensive first pass hepatic metabolism - short t1/2
Therapeutic factors - systemic delivery required but try to avoid oral route
either cyclical or continuous administration required
why do we need alternatives to oral route?
to increase bioavailability and offer sustained release
IM injection transdermal route patch/gel intranasal spray buccal route vaginal gel
Give an example of routes that gives sustained release
IM injection - oily injection for testosterone
implants - nexplanon - prog only contraception
why does oily injection have sustained action?
action because of lower rate of partition from oily vehicle into aqueous environment of tissue.
Testosterone
ester at position 17
decreases water solubility
increases oil solubility
deactivates the molecule so it can’t bind to androgen receptor
the ester is cleaved in blood and restores -OH so can attach to receptor
Release of steroid molecule from oily depots of long-chain esters in muscle tissue
oil has some affinity for water thus allows penetration of water.
the ester is hydrolysed at the surface of the droplet
Subdermal implant of etonogestrol - Nexplanon
nexplanon is a progestogen only contraception
contraception up to 3 yrs
Is intranasal administration systemic or local?
systemic
what are the advantages of intranasal administration?
large surface area
highly vascularised
avoids first pass
good bioavailability for LMW compounds
Disadvantages of intranasal administration?
mucociliary clearance
metabolic activity
poor bioavailability for HMW compounds
is buccal administration systemic or local ?
systemic
Can you administer testosterone buccally?
yes -
Mucoadhesive testosterone buccal delivery system
Sustained release of testosterone
through buccal mucosa
avoids first pass -
Venous drainage from mouth is to superior vena cava, therefore avoids first-pass hepatic metabolism.
is vaginal administration local or systemic?
systemic
vaginal administration - systemic
Crinone - bioadhesive vaginal gel progesterone released over 25-50 hours good patient compliance continous release self insertion / removal
vaginal administration - local
Vaginal ring - Estring
Pessary - oestradiol 10 mcg vaginal tablet insert - Vagifem
Mirena
Intra-uterine progestogen -only device
levonorgestrel (52 mg) released into uterine cavity over 3 or 5 years – local action
T shaped device
How does it work?
thickens cervical mucus to prevent sperm entering uterus
inhibits sperm from reaching egg
thins the uterine lining
Eicosanoid hormones
Local action of PGE2
Prostaglandin E2 - Indicated for the initiation and/or continuation of cervical ripening at or near term when need to induce birth.
