Peptide Depots

Question 1

4 types of long acting HIV prevention

Answer 1

intravaginal ring
implant
injectable
antibody

Question 2

Long-acting injectables

Answer 2

prolong drug action
decrease toxicity
minimize # injections
increase patient compliance and convenience
IM, SC
limited to potent drugs
expensive

Question 3

SR-DDS (formulation w/o structural change of drug substance)

Answer 3

oil/suspension
in situ forming gel
microsphere (depot)

Question 4

microsphere (depot)

Answer 4

use biodegradable polymer as carrier to control drug release
–emulsion type
–spray drying type

Question 5

subcutaneous injection for small MW drugs

Answer 5

e.g. insulin
can enter general circulation directly through blood capillaries

Question 6

subcutaneous large MW molecules

Answer 6

e.g. monoclonal antibodies
must traffic through the interstitial matrix to the peripheral lymphatic system before entering the general circulation at the subclavian vein

Question 7

reservoir matrix

Answer 7

zero order rate, stays within the desired level at a steady state rather than fluctuating

Question 8

diffusion controlled rate

Answer 8

decreasing rate, fluctuates in and out of desired level at peaks and lows, but stays mostly within the bounds. Usually requires more doses

Question 9

Implanon

Answer 9

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

Question 10

biodegradable polymeric depots

Answer 10

inject the degradable polymer containing the drug SC
Upon degradation, the drug enters circulation
sustained release

Question 11

biodegradable polymers

Answer 11

polymer hydrolysis
drug release controlled by bulk degradation of polymer
drug release controlled by surface degradation of polymer, and drug release proportional to SA

Question 12

surface degradation

Answer 12

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

Question 13

Bulk degradation

Answer 13

hydration of microsphere
polymer hydrolysis
peptide dissolution
peptide diffusion
polymer erosion (loss of mass)
PGA, PLA, PLGA

Question 14

polymer hydrolysis

Answer 14

adds water molecule, breaking the bond

Question 15

PGA

Answer 15

highly crystalline
35-40 degrees C
degradation rate 2-3 months
sutures, soft anaplerosis

Question 16

PLA L form

Answer 16

semicrystalline
60-65 degrees C
degradation rate >2 years
fracture fixation, ligament augmentation

Question 17

PLA D, L form

Answer 17

amorphous
55-60 degrees C
degradation: 12-16 months
DDS

Question 18

PLGA

Answer 18

amorphous
45-55 degrees C
1-6 months
suture, fracture fixation, oral implant, drug delivery microsphere

Question 19

Peptide

Answer 19

short chain of AA linked by amide bonds
poor oral bioavailability
poor plasma stability
peptidase-mediated hydrolysis
rapid renal clearance
>50 AA-proteins

Question 20

polypeptides and half life

Answer 20

larger polypeptides–> longer half-life
Half-life is still generally very short

Question 21

peptide drugs

Answer 21

contain PLG microspheres
lyophilized drug substance
release modifier
may be microparticles (most), implant, or solid bolus

Question 22

peptide drug prepartation

Answer 22

protein preparation
encapsulation of protein
final product

Question 23

Lupron injection

Answer 23

prefilled dual chamber syringe (no mixing or refrigeration)
luproloc safety device
fine, 23 gauge needle
closed-system transfer device

Question 24

Uses of lupron

Answer 24

IVF
endometriosis
uterine fibroids
precocious puberty
cancer

Question 25

in situ forming depot (ELIGARD)

Answer 25

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

Question 26

ELIGARD preparation

Answer 26

allow product to reach room temp
assemble syringes
mix throughly for 45 sec
inject at a 90 degree angle SC