Chemicals that form soluble complex molecules with certain metal ions
Increases drug stability
EDTA
Adding EDTA to drug formulations can prevent many types of chemical oxidation
EDTA Chelation Therapy
EDTA forms complexes with toxin
Immune system recognizes EDTA as a threat and detroys EDTA + toxin
Used for lead and heavy metal poisoning
Metal Complexes are held together by noncovalent bonds
False
Noncovalent bonds are involved in the formation of inclusion compounds
True
A-Cyclodextrin is a seven sugar ring
false
6 sugars
Three important properties of cyclodextrin that are responsible for its ability to increase drug solubility
cage like structure
interior hydrophobic, water insoluble drug can be entrapped in cavity
cavity entrances are hydrophillic
Explain why chelate can increase drug stability in solution
chelate froms complex with metal ions in solution
metal ions are most detrimental in oxidation
after chelation metal ions exhibit deminished reactivity
Cyclodextrin could be used to enhance physical and chemical stability of proteins. Why?
CD can minimize protein aggregation
Protein too large to be entrapped in CD
EDTA removes metal ions
Four major interactions among biological molecues
Hydrogen bond
Electrostatic attractions
Van der Waals interactions
Hydrophobic forces
Protein binding effects on drug action
distribution
Tissue penetration
clearance
interactions
Which of the following can be used to describe the hydrogen bond
A.
Which of the following atoms are the electronegative atoms involved in hydrogen bond?
C.
Electrostatic attratction is proportional to the square of the distance between charges (T/F)
False, Inversely proportional
Protein Binding affects the distribution of small molecule drugs (T/F)
True
Generally, only the free drug is available for diffusion and transport to its target cells (T/F)
True
Which of the following interactions is the driving force for the folding of globular proteins?
B.
Which is the most abundant protein in the plasma
A. Albumin
Why EDTA chelation therapy is often administered together with essential nutrients?
A. nutrient enhances binding of EDTA to toxin
B.EDTA may remove important elements (protein, calcium, vitamins, etc.) from the body.
C. Nutrient enhances ability of EDTA to remove toxin
D. All
EDTA may remove important elements (protein, calcium, vitamins, etc.) from the body.
Explain how the drug/protein complex can act as a storage depot in the blood circulation.
only free drug can diffuse into target cells
drug/protein complex stays in blood for prolonged time
d/p complex is reversible during the circulation the complex will dissociate and release the gree drug.
Diffusion
mass transfer of individual molecules
osmosis
passage of water through a semipermeable membrane to dilute solution
Ultrafiltration
separate nanosized particles or macromlecules by differentially permeable membrane
Cross flow filtration
Tangential Flow filtration
Water purification and food industry
Osmotic Drug Release system
Drug layer, push layer and semipermeable membrane
advantage of ultrafiltration vs dead end filtration
Dead end results in a build up of product which may damage product
Ultrafiltration is faster, recovers more product and has a higher filtration rate.
osmosis is the passage of solvent and solute through a semipermeable membrane (T/F)
False, just solvent
Dialysis is a separation process based on unequal rates of passage of solutes and solvent through differentially permeable membrane. (T/F)
True
Which of the following processes is called cross-flow filtration or tangential flow filtration?
B. Ultrafiltration
Which of the following processes is similar to reverse osmosis?
D. Ultrafiltration
Which of the following require energy?
C. Ultrafiltration
Which of the following does not require a membrane?
B.
Eating salty food makes your thristy why?
C.
Two advantages of ultrafiltration in comparison to dead end filtration.
Higher filtration rate
Higher product recovery
Fick's First Law
J=D (dC/dx)
J= diffusion flux
D= diffusion coefficient
C= drug concentration
X= distance of movement perpendicular to the barrier
Lag time
time required for a drug to establish a uniform concentration gradient
Biopharmaceutical classification system
High Permeability: 12
Low Permeability: 34
High Low
Solubility
Dissolution
process of releasing drug out of the solid formulation into solution
Three unique structures of small intestine that account for its large surface area
Microvilli
Villi
Circular folds
O2 and CO2 cross the cell membrane faster than H2O.
True
Cell membrane is composed of two opposing layers of lipids, their hydrophillic tails face one another to form the bilayer core (T/F)
False
Fick's First law of diffusion refers to a nonsteady-state flow. (T/F)
False
The early stage of drug diffusion is the non-steady state condition
True
What is the driving force for Fick's first law?
B. Concentration gradient
The diffusion coefficient of a drug depends on:
D. All
Biopharmaceutical classification systems classifies drugs in terms of their:
C. Solubility and permeability
Which of the following BSC classes is poorest candidate for oral administration?
A. 1
B. 2
C. 3
D. 4
4 is worst, 1 is best
Absorption of BSC class 2 drugs can be improved in the presence of fatty food. Why?
Fatty food induces bile secreation.
Bile enhances drug solubility.
Disintegration Test
To determine wheter tablets or capsules disintegrate within the prescribed time when placed in a liquid medium
Dissolution
process by which drug molecules are released from solid phase into a solution phase.
only drugs in solution can exert effects
dissolution is the limiting step in absorption
dissolution rate reflects the amount of drug dissolved over a given time period
Diffusion layer model
stationary layer of solvent in which the solute molecules exist in concentration from Cs to C.
Diffusion layer can be considered as a diffusion barrier as the membrane in the diffusion process.
Higuchi Model
Q=(2adcst)1/2
Q= drug released per unit area of exposed surface
A= total amount of drug in unit volume of matrix
D=Diffusion coefficient of the drug in matrix
Cs= solubility of drug in polymeric matrix
T=time
Biorelevant medium
Media represents gastric or intestinal environments
Shelf Life
taime at which the active ingredient has decreased to 90% of its original concentration (t90)
Half Life
Time at which active ingredient has decreased to 50% of its original concentration (t1/2)
5 forms of drug instability
I. Chemical Stability
II. Toxicologic Stability
III. Therapeutic stability
IV. Physical stability
V. Microbiologic Stabilty
Major pathways for chemical instability (3)
Hydrolysis
Oxidation
Photolysis
Ideal storage conditions for drugs
cool
dry
dark
Transporter responsible for drug resistance in cancer chemotherapy:
B. Efflux
Most accurate method ot study intestinal drug transportation/absorption.
C. In vivo
Stress may affect drug absorbtion in GI tract (T/F)
True
Poor drug absorption in the stomach is mainly because of its small surface area (T/F)
False
Most drugs are absorbed in the GI tract by the active transport mechanism (T/F)
False
Transporters are not involved in passive diffusion (T/F)
False
Dissolution profile is more dependent on the chemical structure of the active pharmaceutical ingredient (T/F)
False, determined by formulation chemical structure -> absorption
Three examples of modified release dosage:
Extended Release
Enteric coated
Delayed Release
2 differences between carrier-mediated passive transport and active transport
carrier mediated passive transport
no energy required
transport drug from high to low concentration
Active energy is needed
can transport from low to high
Schematic diagram of drug release process from a tablet by disintegration and dissolution
Tablet or capsule-----------------V
Disintegration
Granules or aggregates---->Disolution ----->Drug In Solution-----(absorption)--->Drug in Blood
Deaggregationother fluid and tissues
Fine Particles----------------------^
First order Rate reaction
t1/2=0.693/K
Stress testing
exaggerated storage conditions
Meeting the disintegration test assures the drug release from the formulation (T/F)
False
Dissolution is the limiting step in the absorption of drugs with low permeability.
False
Dissolution provides information on drug absorption across the GI tract (T/F)
False
USP apparatus 1 is a basket method for the dissolution test
True
According to Higuchi model, the amount of drug released is proportional to
A. T
B. T2 C. T1/2 D. T 1/3
C. T1/2
Wich of the following aparatus is the first choice for immediate release formulation?
1
2
3
4
2
Pharmaceutical product should be kept in refridgerator to increase stability (T/F)
False
Bathroom is a good place to store product (T/F)
False
SLEP is available to retail pharmacy (T/F)
False
Stability testing needs to be conducted int he same container closure system proposed for marketing (T/F)
True
Which mechanism is most often responsible for chemical degradation?
C. Hydrolysis
Most common shelf life of products?
1-2 yr
2-3 yr
3-4 yr
4-5 yr
2-3 yr
which of the following tests is used to identify the likely degradation products?
D. Stress test
What is the storage condition for the accelerated testing of drug products intended for storage at room temperature?
C.
What is the testing frequency for accelerated stability testing?
C. 0, 3 and 6 months
Zero Order degradation
C vs T
Linear
Decline over time
First order degredation
lnC vs C
Linear
Decline
Five forms of instability which can lead to the rejection of a drug product
Chemical
Physical
theraputic
toxicologic
microbiologic
4 strategies to prevent oxidation in pharmaceutical product
Protein is a natural polymer, it is composed of 20 different types of amino acids. Select the best description of protein from each category:
Homopolymer/copolymer
Linear/branched/cross-linked
Random/alternating/block/graft
Copolymer
Linear
Random
3 strategies of using polymer in controlled drug release
bioderadable carrier
rate controlling membrane
diffusion matrix
Excipients are used in most drug formulations and they are essential to product performance (T/F)
True
Drug permeability in a polymer's crystalline region is better than that in the amorphous region (T/F)
False
All polymers have Tg and TM. (T/F)
False
Glass transition can only be observed in amorphous region (T/F)
