20. Hormonal drug delivery Flashcards
Examples of dosage forms
IV inhaled Pill/tablet liquid topical
Why do we have dosage forms?
Drug often in powder form
Tiny doses of drug
mg or mcg quantities
Bulk up with excipients
such as water, lactose
Why do we have different dosage forms?
Different clinical conditions e.g. seizure
Different types of patient e.g. children and elderly
Different routes of administration
Different physicochemical properties of drugs e.g. peptide
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
Examples of routes of administration
Transdermal
Occular
Rectal
Types of hormones
Hormones may be categorized into FOUR structural groups:
1. Modified amino acid derivatives – generally orally active. Derived from tyrosine or tryptophan e.g. dopamine, thyroxine
- Peptide and proteins – vary considerably in size from 3 amino acids to large, multisubunits glycoproteins.
Susceptible to enzymatic degradation in GIT
Low absorption
Derived from amino acids e.g. neuropeptides (vasopressin), pituitary hormones (gonadotropins), GI hormones (insulin) - Steroids – lipids derived from cholesterol
e.g. sex hormones
Variable absorption
Susceptible to extensive first pass hepatic metabolism, corticosteroids (hydrocortisone)
Orally active BUT systemic SIDE EFFECTS - Eicosanoids (derived from lipids) e.g. prostaglandins, leukotrienes
Factors concerning modified amino acid derivatives e.g. thyroxine and corticosteroids e.g. hydrocortisone
Drug factors:
- Low dose required
Biopharmaceutical factors – which route?
- Orally bioavailable
Therapeutic factors:
- Local vs. systemic delivery
What are excipients?
Excipients are anything else that is part of the dose which is not the drug: Diluents/fillers 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 ~5800 Da
Biopharmaceutical factors:
- Not absorbed after oral administration
Therapeutic factors:
- Need systemic action
- Aim to mimic insulin secretion by normal pancreas
- basal and bolus
Insulins 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
Long acting insulins
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®).
Continuous subcutaneous insulin infusion
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.
Pulmonary route can be used for 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
