Principles of controlled drug delivery systems

What are the key considerations in drug delivery?

-drug "personality"

-dose/quantity/accuracy

-bioavailability

-stability

-manufacturability

-product acceptance

What are properties to consider when manufacturing a drug product?

-drug concentration

-pH

-diluent type/concentration

-oxygen

-light

-freezing effect

-drug stability

-buffer type/concentration

What are the elements of drug delivery?

-drug

-excipients

-packaging

What is the personality of a drug?

intrinsic chemical and physical characteristics that must be considered before the start of formulation

What are drug intrinsic chemical and physical characteristics?

-solubility

-partition coefficient

-dissolution rate

-physical form

-stability

What are the benefits of excipients?

-manufacturability

-stability

-bioavailability

-accurate dosing

-patient acceptance and convenience

What are types of solids?

-powders

-capsules

-tablets

-implants

What are types of liquids?

-solutions

-suspensions

What are types of semi-solids?

-ointments, creams

-suppositories

What are the categories of drug delivery?

-immediate release

-delayed release, then full release

-prolonged release

-controlled release

What is distribution?

movement of drug from blood to and from tissues

What is involved in distribution?

-partitioning across membranes

-tissue and protein binding

-physiological volumes

What are factors influencing drug response?

-density of surface receptors

-mechanism of signal transduction

-regulatory factors that control gene translation and protein production

What is drug potency measured by?

EC50

What is EC50?

concentration at which 50% of the max effect

What does lower EC50 indicate?

higher potency

What is tolerance?

effectiveness decreases with continual use

What can cause tolerance?

-PK

-PD

-opiates in the management of chronic pain

What is the therapeutic index(TI)?

degree of separation between toxic and therapeutic doses

What drugs is the TI narrow for?

chemo drugs

What are the parts of the transdermal drug device?

-backing

-reservoir of the drug

-microporus membrane

-contact adhesive

What structure does the drug take advantage of in pulmonary delivery?

alveoli

What are the main goals of controlled local drug delivery?

-minimum systemic absorption

-optimal drug concentration reaches local site

What is involved in spatial control?

Active and Passive Targeting

What is active targeting?

site specificity, target specific ligand

What is passive targeting?

no ligand needed, depends on blood flow, particle size, permeability

What is involved in temporal control?

-controlled release

-stimuli-responsive release

-self-regulating release

What DDS can improve poor solubility?

lipid micelles or liposomes provide both hydrophilic and hydrophobic environments

What DDS can improve tissue damage on extravasation?

regulated drug release can reduce or eliminate tissue damage

What DDS can improve rapid breakdown of drug in vivo?

protect the drug from premature degradation and functions as sustained release. lower doses required

What DDS can improve unfavorable PK?

alter the PK and reduce clearance, rapid renal clearance of small molecules is avoided

What DDS can improve poor biodistribution?

-lowers the volume of distribution

-helps reduce side effects

-increase drug concentration in diseased tissues

-ligand-mediated targeting

What are the problems with small molecule drugs?

-solubility

-oral bioavailability

What are the problems with peptide drugs?

-solubility

-stability

What are the problems with protein drugs?

-stability

-aggregation

What are the problems with MAb drugs?

-solubility/viscosity

-aggregation

What are the problems with oligonucleotide drugs?

-targeting

-stability