Pharmaceutical Technologies (Parenteral and Transdermal Delivery) Flashcards
What is the difference between epidural and intrathecal delivery?
- IT = Deliver into cerebrospinal fluid
- Epidural = Deliver into reservoir / lower back (Have to diffuse across epithelial layer)
What is the ebb and flow circulation of CSF like?
Direction is promoted by source and cilia
What are the common barriers of parenteral delivery?
- BBB (Non-intrathecal only)
- Dilution / Distribution (Mainly non-intrathecal; Intrathecal within the CSF compartment)
- Reticuloendothelial system
- Metabolic enzymes
- Invasive
- Medical Professional needed
- Sterility is strict
What are the advantages of parenteral delivery?
M: No hepatic first pass
A: Control dosage (Lower drug conc, toxicity)
D: Direct access to the brain
A: Sustained release (IM depot, IT reservoir)
Patient: Non-compliant, unconscious, dysphagic pt
What are the three transporters in the BBB?
- Active efflux transporters (Pgp, BCRP, MRP)
- Carrier mediated transporters
- Receptor mediated transporters (Transcytosis)
What is the modified Lipinski’s rule of 5 for CNS?
MW < 450 Da
H bond donor < 3
H bond acceptor < 7
LogP 1-3
Unionizable
What excipients are needed for injection?
Diluent
Buffer salts
Tonicity adjusters
Stabilizers / Co-solvents
Minimally preservatives because it can complicate and cause brain inflammation
What pH, tonicity and particle size considerations are required in injections?
pH 7.4 (IM: 3-11; SQ 3-6)
Tonicity 280-290 mOsm/L for large volume (Hypertonic preferred)
No visible particles size for IV (Less for SQ, IM)
Examples of excipients for injections
Buffers = Acetate, citrate, phosphate, lactate
Preservative = Alcohol, Parabens
Tonicity adjuster = Mannitol, NaCl
Solvents = Ethanol, glycerol, PEG, propylene glycol
What is the primary anatomical barrier for drug delivery across the skin?
Stratum Corneum
- Brick and Mortar structure is an ordered and rigid bilayer structure
- Access occurs through intercellular lipid domains and appendages (follicles, ducts)
Differentiate transdermal and topical delivery
Transdermal = Deep penetration and Systemic Delivery (Usually Patch)
Topical = Superficial and Local Delivery (Usually gels and cream)
5 advantages of transdermal delivery
o Controlled release (reservoirs, duration of contact) = Decreased dosing frequency
o No GI degradation/irritation
o Bypasses hepatic first pass effect
o Easy termination of input
o Non-invasive
7 Barriers to transdermal delivery
o Variability between people and location of administration on body
o Stratum corneum: Slow absorption
o Skin irritation (interactions and removal)
o Could be removed by the patient
o Metabolic enzymes
o Blood brain barrier (via systemic delivery)
o Systemic side effects
What are the factors that affect transdermal delivery?
o Skin condition: age, disease, injury, site
o Skin thickness (thickness of diffusion layer)
o Hydration of skin (stratum corneum) - Natural or “manufactured” (occlusive: physical/chemical)
o Stimulation of the skin (phonophoresis/ ultrasound, iontophoresis, heat)
o Physicochemical properties of drug (lipophilicity, diffusion coefficient)
o Permeation enhancers - Reversible reduction in the barrier resistance of the stratum corneum without damaging viable cells
o Concentration gradient
o Area of contact between formulation and skin
What is the modified Lipinsky’s rule for Transdermal Delivery
LogP 1-3 is the only difference
