Formulation and delivery of Insulin Flashcards
What are the main differences between a small molecule and therapeutic protein
Small molecule: typical drug
Carbon chain
Low homogenous
Site of action delivery
Therapeutic protein:
Hydrophilic to polypeptide
High single protein with moderate heterogeneity
Site of action: Insulin, flu vaccines
What are the four categories for biologicals and give examples of each
- Gene therapy (nucleic acid)
Gendicine - Polypeptides
Proteins and peptides- insulin, growth hormone, clotting/blood factors - Monoclonal antibodies
Trastuzumab- herceptin
Rituximab- Mabthera
Infliximab- Remicade - Vaccines
Influenza vaccine
BCG tuberculous vaccine
Hepatits B
What are the three challenges for all biologics
Complexity- higher than normal drugs
Instability- biological origin makes it more unstable
Availability- often limited by large molecular size
What is immunogenicity
Immune response to drug (hypersensitivity)
Leads to loss of efficacy and more serious adverse effects
Why are biologics so unstable
Biological origin
Conditions must be compatible with biological molecules- good food for microbes
Proteins have 3-4 layers of vital structure that can degrade with reactions via H2O and O2- irreversible change
What are the four protein structures and describe each one briefly
Primary structure- amino acid sequence
Secondary structure- regular sub structures (alpha helix and beta sheet)
Tertiary structure- 3D structure
Quaternary structure- complex protein molecule
How do you normally deliver biologics and why these routes
Biologics have large molecular size
- Permeability through epithelia (biomacromolecules wont pass through here though)
- Access to tissues from blood vessels
- Cell membranes- although drug target not normally within cells
What are the two methods of manufacturing proteins and examples of proteins made by each of these methods
Biotechnology: Produced in microbial or animal cell cultures and isolated via chromatographic and filtration steps
Example: Insulin, erythropoietin, monoclonal antibodies and interferons
Isolate from blood:
Examples: albumin and blood clotting factors
focused on reduction of viral contamination
What are the four different types of insulin
Rapid Acting
Short Acting
Intermediate Acting
Long Acting
Describe rapid acting insulin and give some examples
Short onset of action and short duration time
examples: Insulin Lispro (Humalog) Insulin Aspart (NovoRapid) Insulin glulysine (Apidra)
Describe long acting insulin and give some examples
Longer effect than intermediate acting insulins
Normally used ONCE daily to maintain basal insulin level (2-4 days achieves steady state)
Examples: Insulin glargine (LANTUS) Insulin determir (levemir) Insulin degludec (tresiba)
What are the different ways insulin forms are modified
Modification of aggregation, quaternary structure and crystallinity alters SOLUBILITY and AVAILABILITY
What are the three basic insulin regimes and describe each of them
- ONE, TWO or THREE insulin injections per day:
Short acting or rapid acting insulin analogue with an intermediate acting insulin - MULTIPLE DAILY INJECTIONS
Short acting or rapid acting insulin analogue injected BEFORE MEALS
Can be used together with one or more separate daily injections of intermediate acting or long acting - CONTINUOUS SUB CUTANEOUS INSULIN INFUSION
Includes: Programmable pump that delivers a regular continuous amount of insulin that is short or long acting- via subcutaneous needle or cannula
What are the different devices available for insulin administration
- Pre-filled injectors (subcutaneous)
- Syringe and needle
- Injectors and auto injectors
- Needle free injectors
- Pumps
What are the future insulin delivery methods that are thought to be in development
Needle free injectors
Inhaled
Transdermal
Oral insulin- micro encapsulation
