Hormonal drug delivery

Question 1

Why do we have dosage forms?

Answer 1

Drug often in powder form
Tiny doses of drug - mg or mcg quantities
Bulk up with excipients - such as water, lactose

Question 2

Why do we have different dosage forms?

Answer 2

Different clinical conditions - e.g. local treatment for eczema.
Different types of patient - e.g. tablets typically not given to children under 6.
Different routes of administration - due to bioavailability.
Different physicochemical properties of drug.

Question 3

Give some examples of routes of administration and their dosage form respectively

Answer 3

rectal - suppository.
oral - tablets capsules, liquids.
parenteral - injection.
intranasal - nasal prays or drops.

Question 4

What are the types of hormones?

Answer 4

Modified amino acid derivatives (derived from tyrosine or tryptophan) - generally orally active.
Peptide and proteins (derived from amino acids) - susceptible to enzymatic degradation in GIT, low absorption.
Steroids (derived from cholesterol) - susceptible to extensive first pass hepatic metabolism. corticosteroids are orally active but have systemic side effects.
Eicosanoids (derived from lipids).

Question 5

What are the features of local delivery?

Answer 5

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

Question 6

Which dosage forms are required for local delivery of corticosteroids?

Answer 6

To avoid systemic side effects need many different dosage forms:
Intra-articular injections – tennis elbow
Creams and ointments - eczema
Inhalers - asthma
Eye drops - inflammation
Suppositories - haemorrhoids

Question 7

What are the drug factors, biopharmaceutical factors and therapeutic factors for peptide hormones such as insulin?

Answer 7

drug factors: peptide hormone, large molecule MW.
biopharmaceutical: not absorbed after oral administration.
therapeutic factors: need systemic action. aim to mimic insulin secretion by normal pancreas - basal and bolus.

Question 8

Insulin is characterised by differences in which features?

Answer 8

Onset, peak, duration, route of delivery

Question 9

What are alternatives to injectable insulin?

Answer 9

Continuous subcutaneous insulin infusion (CSII) of rapid analog.
Inhaled insulin – Afrezza: rapid-acting inhaled insulin. taken at beginning of each meal. used in combination with a long-acting injected insulin.

Question 10

Why is the pulmonary route good for systemic delivery?

Answer 10

Large surface area, thin epithelial barrier, good blood supply, avoids harsh environment of GI tract, avoids first-pass hepatic metabolism.

Question 11

What are the drug factors, biopharmaceutical factors and therapeutic factors of sex hormones?

Answer 11

Drug factors: steroid, lipophilic.
Biopharmaceutical: variable absorption after oral administration. extensive first pass hepatic metabolism, short t1/2.
Therapeutic: systemic delivery required but try to avoid oral route. either cyclical or continuous administration required.

Question 12

Why are alternatives to the oral route required?

Answer 12

to increase bioavailability and to offer sustained release

Question 13

Which routes and dosage forms provide systemic delivery?

Answer 13

Parenteral route - IM injection, implant
Transdermal route - patch or gel
Intranasal route - spray
Buccal route – mucoadhesive system
Vaginal – gel

Question 14

Give examples of IM injections

Answer 14

Oily injections – sustained release - testosterone enantate (caster oil)
Implants – sustained release - progestogen-only contraception (systemic delivery)

Question 15

What is the purpose of the ester group replacing the OH group for testosterone?

Answer 15

Decreases water solubility, increases oil solubility, deactivates molecule - can’t bind to androgen receptor,
Ester cleaved in blood - restores OH so can attach to receptor.

Question 16

What are the advantages and disadvantages of intranasal administration - systemic and give an example?

Answer 16

Large surface area, highly vascularized, avoids first pass hepatic metabolism, good bioavailability for low MW compounds.
Mucociliary clearance, metabolic activity, poor bioavailability for high MW compounds.
Desmopressin.

Question 17

Give an example of buccal administration - systemic

Answer 17

Mucoadhesive testosterone buccal delivery system.
Applied twice daily, adheres to gum or inner cheek,
sustained release of testosterone through buccal mucosa

Question 18

What are the features of vaginal administration - systemic and give an example?

Answer 18

Self-insertion and removal, continuous release, good patient compliance.
Bioadhesive vaginal gel (Crinone - prog released over 25 – 50 h).

Question 19

Give an example of a vaginal administration (local) - device

Answer 19

Vaginal ring (Estring) - estradiol released over 90 days

Question 20

Give an example of a vaginal administration (local) - pessary

Answer 20

Estradiol 10 mcg vaginal tablets (inserts) (Vagifem)

Question 21

What are eicosanoid hormones and what are their dosage forms?

Answer 21

Prostaglandin E2
Vaginal gel
Vaginal pessary/tablet (Propess)
PGE2 released over 12 hours, local action to ripen cervix