13 - Protein & Peptide Flashcards
Example of a protein peptide drug?
Insulin
Under 40 amino acids long = _____
peptide
Over 40 amino acids long = ______
protein
Peptides/Proteins are naturally abundant where?
in vivo and in vitro
List some characteristics of peptides/proteins
- low dose
- specific selectivity
- biocompatibility
- biodegradability
- minimal adverse effects
- large molecules
- labile configuration
- instability
- special in vivo profile
- targeting difficulty
- low overall therapeutic outcomes
Peptides/Proteins can undergo denaturation; give a good example of denaturation
boiling eggs
There is 4 phases of denaturation; describe them
Primary: uncoiling
Secondary: (??? not in my notes)
Tertiary: starts to interact with itself through H bonding
Quaternary: one protein peptide interacts with another peptide
What is the traditional administration type for proteins/peptides?
parenteral
What are some novel administration types for proteins/peptides?
- pulmonary
- nasal
- ophthalmic
- buccal/SL
- rectal
- transdermal
- oral
What factors affect stability?
- pH
- temp
- ionic strength
- freeze/thaw effects
- organic solvents
- light
- oxygen
- surfactants
- radiation
- residual moisture
- shear forces
- interfacial adsorption
- heavy metal ions
What is preformulation?
“before formulating” - Kelsey
LOL
taking a look at all the characteristics of the drug before formulating it
What factors are taken into consideration in preformulation?
- structure
- molecular weight
- pH solubility
- pH conformation
- air-water interface
- freeze/thaw effect
- solvent compatibility
- degradation
- melting point
- absorbance spectra
- solvate formation
- polymorphism
- hygroscopicity
- stability tests
What characteristics do you want for in vivo performance?
- various sites from different enzymes
- quick degradation and metabolism
- short half-life
- reach action site with minimal destruction
Describe conventional parenteral dosing
- feasible/practical
- easy processing
- low unit cost
- instability
- bioavailability deficiency
- drug targeting difficulty
Describe novel parenteral dosing
- feasible/difficult
- improved stability
- potential site target
- better bioavailability
- complex processing
- high unit cost
- large-scale production difficulty
Anything over ____ microns would usually get stuck in the back of the throat
10
Describe pulmonary absorption
- systemic absorption and action
- fast absorption
- fast onset of action
- relatively large absorption area
- relatively mild absorption environment
- relatively acceptable approach
- relatively feasible production
_____ is currently being processed to be able to be inhaled instead of injected
insulin
List some surfactants
- tween
- span
- sodium laurel sulfate
- glyceryle monostearate
Why do we need an excipient to enhance absorption of peptides/proteins administered rectally?
because the protein is so large
Describe vaginal application of proteins/peptides
- provides sustained drug action
- similar to SC implant
- has shown significant regression of tutors in rats
Advantages of oral administration of proteins/peptides
- convenient
- non-invasive
Barriers to oral administration of proteins/peptides
- extreme environment
- extensive metabolism
- various absorption barriers (pH, enzymes, food)
- difficult drug targeting
- cost
List some strategies to improve peptides into an oral drug dosage form
- protectant so enzymes don’t get at it
- structure modification
- absorption enhances
- protease inhibitors
- controlled drug release
- specific site targeting
Describe structure modification
- conjugates
- prodrugs
- pH resistant structure
- enzyme resistant structure
- balance between hydrophilic and lipophilic properties
Describe absorption enhances
- absorption facilitator
- surfactants or other macromolecules
- disturbance of normal GI structures
- potential pharmacologic activity
- potential interactions
- long-term toxicity/side effects
*surfactant = most common
Describe protease inhibitors
- absorption facilitator
- macromolecules that deactivate enzymes
- physical/chemical incompatibility
- possible total function shutdown
- risk/benefit evaluation
- highly controversial and used with caution
Describe controlled drug release
- structure protector
- various established polymers and techniques
- no adverse effects
- more effective together with other strategies
Describe specific site targeting
- mostly theoretical
- external guidance to or retention on target (mostly local target)
- no adverse effects
- assessment of in vivo effectiveness
- more effective in combination with other approaches
What are some different preparations?
- liposomes
- microemulsions
- microcapsules/microspheres
- bioadhesive formulations
- solid formulations
