Peptide Depots Flashcards
4 types of long acting HIV prevention
intravaginal ring
implant
injectable
antibody
Long-acting injectables
prolong drug action
decrease toxicity
minimize # injections
increase patient compliance and convenience
IM, SC
limited to potent drugs
expensive
SR-DDS (formulation w/o structural change of drug substance)
oil/suspension
in situ forming gel
microsphere (depot)
microsphere (depot)
use biodegradable polymer as carrier to control drug release
–emulsion type
–spray drying type
subcutaneous injection for small MW drugs
e.g. insulin
can enter general circulation directly through blood capillaries
subcutaneous large MW molecules
e.g. monoclonal antibodies
must traffic through the interstitial matrix to the peripheral lymphatic system before entering the general circulation at the subclavian vein
reservoir matrix
zero order rate, stays within the desired level at a steady state rather than fluctuating
diffusion controlled rate
decreasing rate, fluctuates in and out of desired level at peaks and lows, but stays mostly within the bounds. Usually requires more doses
Implanon
contraceptive implant
one poly EVA tube filled with poly EVA matrix containing particles of 3-keto-desogestrel
Thickness of outer membrane - 0.06mm
zero order drug release
EVA is the rate controlling membrane
biodegradable polymeric depots
inject the degradable polymer containing the drug SC
Upon degradation, the drug enters circulation
sustained release
biodegradable polymers
polymer hydrolysis
drug release controlled by bulk degradation of polymer
drug release controlled by surface degradation of polymer, and drug release proportional to SA
surface degradation
polyanhydride
gliadel wafer contains BCNU
surgeon operates to remove glioblastoma multiforme
8 dime-sized gliadel wafers placed in space tumor occupies
wafers slowly dissolve bathing the surrounding cells with BCNU for 2-3 weeks
zero-order drug release, constant SA
Bulk degradation
hydration of microsphere
polymer hydrolysis
peptide dissolution
peptide diffusion
polymer erosion (loss of mass)
PGA, PLA, PLGA
polymer hydrolysis
adds water molecule, breaking the bond
PGA
highly crystalline
35-40 degrees C
degradation rate 2-3 months
sutures, soft anaplerosis
PLA L form
semicrystalline
60-65 degrees C
degradation rate >2 years
fracture fixation, ligament augmentation
PLA D, L form
amorphous
55-60 degrees C
degradation: 12-16 months
DDS
PLGA
amorphous
45-55 degrees C
1-6 months
suture, fracture fixation, oral implant, drug delivery microsphere
Peptide
short chain of AA linked by amide bonds
poor oral bioavailability
poor plasma stability
peptidase-mediated hydrolysis
rapid renal clearance
>50 AA-proteins
polypeptides and half life
larger polypeptides–> longer half-life
Half-life is still generally very short
peptide drugs
contain PLG microspheres
lyophilized drug substance
release modifier
may be microparticles (most), implant, or solid bolus
peptide drug prepartation
protein preparation
encapsulation of protein
final product
Lupron injection
prefilled dual chamber syringe (no mixing or refrigeration)
luproloc safety device
fine, 23 gauge needle
closed-system transfer device
Uses of lupron
IVF
endometriosis
uterine fibroids
precocious puberty
cancer
in situ forming depot (ELIGARD)
drug in syringe A + biodegradable copolymer (PLG) and bicompatible lipid carrier (NMP) in syringe B
PLG solidifies in body due to NMP and water in body
ELIGARD preparation
allow product to reach room temp
assemble syringes
mix throughly for 45 sec
inject at a 90 degree angle SC
