Hormonal drug delivery Flashcards
Why do we have dosage forms?
Drug often in powder form
tiny doses of drug
Bulk up with excipients
Reasons for different dosage forms
Different clinical conditions
Different types of patients
Different routes of administration
Different physicochemical properties of drug
Factors to consider when designing dosage forms
Drug factor
- solubility, partition coefficient, pKa, stability, MWt
Biopharmaceutical factors
- absorption, bioavailability, route of administration
Therapeutic factors
- disease, patient, route, local vs systemic delivery
Types of hormone
Modified amino acid derivatives
- derived from tyrosine or tryptophan
- dopamine, thyroxine
Peptide and proteins
- derived from amino acids
- e.g. neuropeptides, pituitary hormones, GI hormones
Steroids
- derived from cholesterol
- e.g. sex hormones, corticosteroids
Eicosanoids
- derived from lipids
- prostaglandins, leukotrienes
Modified amino acid derivatives and corticosteroids
Drug factors
- low dose required
Biopharmaceutical factors
- orally bioavailable
Therapeutic factors
- local vs systemic delivery
Small drug dose
e.g. 25mcg
Add excipients to make it manageable
- diluents e.g. lactose, water
- surfactants e.g. polysorbates
- lubricants e.g. mg stearate
- disintegrants e.g. starch
- viscosity enhancing agents e.g. cellulose derivatives
- flavours, colours, perfumes
- sweetening agents
- preservatives
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
Local delivery of corticosteroids
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
Peptide hormone
e.g. insulin
Drug factors
- peptide hormone, large molecule MW
Biopharmaceutical factors
- not absorbed after oral administration
Therapeutic factors
- need systemic action
- aim to mimic insulin secretion by normal pancreas
Insulin characterised by differences in
Onset
- how quickly they act
Peak
- how quickly they achieve maximum impact
Duration
- how long they last
Route of delivery
- subcutaneous, inhaled
Pulmonary route
Systemic delivery
- large surface area
- thin epithelial barrier
- good blood supply
- avoids harsh environment of GI tract
- avoids first pass hepatic metabolism
Inhaled insulin
Rapid acting inhaled insulin
Taken at the beginning of each meal
Used in combination with a long acting injected insulin
Sex hormones
Drug factors
- steroid, lipophilic, MW 270
Biopharmaceutical 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
IM injection
Oily injections- sustained release
- testosterone enantate
- testosterone decanoate, isocaprate, phenylpropionate and proprionate, undecanoate
Implants- sustained release
- nexplanon (progestogen only contraceptive)
Ester at position 17 (testosterone)
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
Advantages of intranasal administration
Large surface area
Highly vascularised
Avoids first pass hepatic metabolism
Good bioavailability for low MW compounds
Disadvantages of intranasal administration
Mucociliary clearance
Metabolic activity
Poor bioavailability for high MW compounds
Buccal administration
Mucoadhesive testosterone buccal delivery system
Applied twice daily
Adheres to gum or inner cheek
Sustained release of testosterone through buccal mucosa
Vaginal administration
Local
Self insertion and removal
Continuous release
Good patient compliance
e. g. bioadhesive vaginal gel (progesterone released over 25-50h)
e. g. vaginal ring (estradiol released over 90 days)
e. g. pessary, estradiol 10mcg vaginal tablets
Intrauterine progestogen only device
IUS (mirena, jaydess, levosert)
Levonorgestrel released into uterine cavity over 3 or 5 years
Local action
Eicosanoid hormones
Prostaglandin E2 (prostin E2, dinoprostone)
Vaginal gel
Vaginal pessary/ tablet
Agonist/ antagonist: growth hormone
Agonist: somatropin, mecasermin
Use: growth disorders
Antagonist: pegvisomant
Use: acromegaly
Agonist/ antagonist: oxytocin
Agonist: oxytocin
Use: induction of labour, post partum haemorrhage, incomplete abortion
Agonist/ antagonist: prolactin
Antagonist: bromocritine, cabergoline, quinagolide
Use: hyperprolactinaemia
