Ips3 Jasti

Front 1

Draw Backs to IV drug administration

Back 1

1. Reserved for
-- Critically ill patients
-- Hospitalized patients
-- Extravascular dosage forms can not be admistered

In Outpatients: ORAL dosage preferred

Front 2

Terminology

Modified-release Dosage Froms

Back 2

1985 - USP/NF

-Describes dosage forms that alter the timing and rate of release of the drug from the drug product

Ex:
-- Extended-release dosage forms
-- Delayed-release dosage froms

Front 3

Define

Extended-Release Dosage From

Back 3

-allows two fold reduction in dosing frequency

-Controlled-release products are considered extended-release dosage forms

Front 4

Define

Delayed-Release Dosage From

Back 4

-dont have immediate drug release. drug release in parts or times other than promptly after administration.
-Sometimes designed to have immediate drug release and than delayed release with adminstration

Ex: Enteric-coated tablets

Front 5

Define

Targeted-Release Dosage From

Back 5

-drug release at or near the site of action

-may have immediate or extended-release characteristics (not all are sustained release)

Front 6

Define

Sustained-action release

Back 6

-immediate loading dose followed by prolonged release of drug

Loading Dose + Prolonged Release

-any dosage form that provides medication over an extended time (timed release, prolonged release)

Front 7

Define

Prolonged-action release

Back 7

-drug release over a long period of time.

-drug release may or may not be immediate

Front 8

Define

Controlled-action release

Back 8

-you can tell at what which rate the drug is being released from the dosage from.

Space: Spatial - targeted to site. Time: Temporal - time controlled

-denotes that system is able to provide some actual therapeutic control (temporal nature, spatial nature, or both).
-also may be able to promote localization of drug at a active site, along with 0-order delivery.

Front 9

Goals of drug delivery systems?

What roles doe modified drug delivery systems play in order to achieve the drug delivery system?

Back 9

1. Deliver adequate amount of drug to site of action
-Provide and maintain: (Max therapeutic effect, max safety, max reliability)

2. with MDD system we can control: (onset, duration, intensity, elimination, distribution).
-- this allows for optimum therapeutic benefit consistent with safety and reliablity

Front 10

Benefits of Modified Release Dosage Froms

Back 10

- Drug levels maintained in desired range
- Side Effects minimized
-helps short half-life drugs
- enhances compliance
- lowers cost
- health care in remote areas made easier

Front 11

Requirements for Modified Release Dosage froms

Back 11

1. Patient monitoring (possible drug dumping)

2. Patient Education (crush or chew)

Front 12

Covera HS

Back 12

Verapamil

Class IV antiarrythmic drug (Calcium Channel Blocker)

-taken at bed time, stays in system over night, prevents MI due to postural hypotension

Front 13

Verapamil

Back 13

Cover HS

Class IV antiarrythmic drug (Calcium Channel Blocker)

-taken at bed time, stays in system over night, prevents MI due to postural hypotension

Front 14

Examples of times when you dont need constant drug levels

Back 14

1. Diabetes
2. Circadian rythms
-- Oral Contraceptives
-- Bronchial Dyspnea
-- COPD
-- Hypertension (Covera)

Front 15

Preferred mechanism of Drug Release

Back 15

1. Zero-order release

2. First-order release
**if you slow down the release of the drug, it will get close to the 0-order release**
-this works with drugs with a short therapeutic window

Front 16

Two basic approaches for controlling drug availability?

Back 16

1. Drug Design (takes too long, FDA approvals needed)

2. Product Design
- shorter development time &
- less money used

Front 17

Terminology

used for identification in market

Back 17

Sustained Release
Prolonged Release
Extended Release

Front 18

Terminology

Repeat Action

Back 18

stimulates sustained release

Front 19

Complete the Tree


1. Diffusion Controlled
2. Dissolution Controlled
3. Osmotically Controlled

Back 19

1. Diffusion Controlled
- Reservoir
- Matrix (erodible & non-erodible)

2. Dissolution controlled
- Noyes Whitney Equation
- Hixon Crowell Equation
- Single Bead vs. Multiple Beads

3. Osmotically Controlled
-Type A - Drug & Osmotic core TOGETHER
-Type B - Drug & Osmotic core SEPARATE

Front 20

Complete the Tree


4. Biodegradable
5. Ion-Exchange Systems
6. Targeted Delivery Systems

Back 20

4. Biodegradable
-Mechanisms I-IV
-1. Soluble; 2. Insoluble to solubline; 3. Drug trapped inside polymer; 4. Drug cleavage from polymer

5. Ion-Exchange Systems
-Penn-Kinetic System

6. Targeted Delivery Systems
-Liposomes & Nanoparticles (passive)
-Resealed Erythrocytes
-Monoclonal antibodies (active)

Front 21

Define Prodrugs &
advantages of their use &
Classifications

Back 21

-Latentiated form of a drug which must undergo biotransformation in vivo to become activated. NO INHERENT PHARMACOLOGICAL ACTIVITY

Advantages: improved bioavailability, patient acceptability, stability

Classes: Esters, Amides, Salts

Front 22

7 Prodrug Examples

Back 22

1. Pivampicillin (ampicillin) - absorption
2. L-Dopa (Dopamine)- BBB cross
3. Dipivalyl Epinephrine (Epi) - stable, 10X better F
4. Testosterone Palmitate (testosterone) - Longer DOA, better F
5. Chloramphenicol Palmitate (not bitter)
6. Clindamycin Phosphate (No IM injection irriation)
7. Erythromycin Estolate (Inc. GI tract stabilility)

Front 23

Pivampicillin

Back 23

Prodrug

-Ampicillin
-Better absorption of Prodrug

Front 24

L-Dopa

Back 24

Prodrug

-Dopamine
-Crosses BBB

Front 25

Dipivalyl Epinephrine

Back 25

Prodrug

-Epinephrine (ex: Propine)
-Prodrug is more stable & better bioavailability(10x)

Front 26

Propine

Back 26

Prodrug: Dipivalyl Epinephrine

-Epinephrine (ex: Propine)
-Prodrug is more stable & better bioavailability(10x)

Front 27

Testosterone Palmitate

Back 27

Prodrug

-Testosterone
-Better bioavailability & longer duration of action

Front 28

Chloramphenicol Palmitate

Back 28

Prodrug

-No bitterness

Front 29

Clindamycin Posphate

Back 29

Prodrug

-NO IM injection irritation

Front 30

Erythromycin Estolate

Back 30

Prodrug

-Better Stability in GI tract

Front 31

Prodrug Class:

Ester Prodrug advantages

Back 31

1. Better Taste
2. Increased solubility
3. Improved absorption
4. Increased oral absorption
5. Extended duration
6. Target to specific transporters

Front 32

Prodrug Class:

Amide Prodrug advantages

Back 32

1. Decreased GI irritation
2. Prolonged Action

Front 33

Prodrug Class:

Salt Prodrug advantages

Back 33

Improved Stability

Front 34

List two DIFFUSION controlled delivery systems

Back 34

1. Reservior systems

2. Matrix Systems

Front 35

List the 4 polymers used in a Reservior system

Back 35

1. Ethyl cellulose

2. EVA (ethylene-vinyl acetate copolymer)

3. Celluloses
-- HPMC (hydroxypropyl methyl cellulose)
-- PEG (Polyethylene glycol)

Front 36

Define:

Microencapsulation

Back 36

Process in which the small beads, used in a reservior system, are created.

Front 37

Define:

Reservior System

Back 37

-A core of drug (reservoir) surrounded by an inert polymeric membrane
-Any shape or size
-microencapsulation process used to create it

Front 38

Reservior Systems

Mechanism of Drug release

Back 38

-Diffusion controlled drug release.

-Rate of drug release is controlled by the rate of diffusion across the polymer coating

Front 39

Advantages of Reservoir Systems

Back 39

-Zero-order release is possible

-Release kinetics may be easily controlled by parameters
A. Polymer content (thickness)
B. Pore former in the film (diffusion coefficent)
C. Drug Load (Concentration)
D. Drug solubility (change in concentration)

Front 40

Disadvantages of Reservoir System

Back 40

-Lag time (freshly made)
-Burst Effect (been on shelf)

-If implanted, must be removed
-leaks are dangerous (toxic drug dumping possible)

Front 41

Bayer timed-release aspirin

Back 41

Reservoir System

Front 42

Nitroglycerin Extended-Release capsules

Back 42

Reservoir System

Front 43

Nitro-bid

Back 43

Reservoir System

Front 44

Define:

Matrix Systems

Back 44

Dissolution Controlled Delivery System

-Drug is dispensed in a solid dispersion medium which is insoluble (non-erodible) or less soluble (erodible) than the drug

Front 45

Non-Erodible Matrix Systems

-Drug type to use
-5 Polymers to use

Back 45

Drugs: Good for soluble drugs

Polymers
1. Waxes
2. Glycerides
3. Long chain fatty acids
4. EC (ethyl cellulose)
5. Methacrylate

Front 46

Erodible Matrix Systems

-Drug type to use
-5 Polymers to use

Back 46

Drug: Good for poorly soluble drugs

Polymers
1. HPMC (Hydroxypropyl methyl cellulose)
2. PEO (Polyethylene oxide) (High MW PEG)
3. HPC (Hydroxypropyl cellulose)
4. HEC (Hydroxyethyl cellulose)
5. Polyacrylic acid (Carbopol)

Front 47

Matrix System

Mechanism of Drug Release

Back 47

-Drug is in the exterior regions of the device is dissolved first and diffuses out of the matrix. (This process continues until the device is exhausted)
-Diffusion controlled: rate of dissolution of drug has to be much faster than rate of diffusion of drug.

Front 48

Matrix Systems: Higuchi Equation

Non-porous hemogenous matrices, K (the rate constant) depends on...

Back 48

M = K * t^0.5

1. Concentration of drug in the matrix
2. Diffusion coefficent in teh matrix

Front 49

Matrix Systems: Higuchi Equation

Porus hemogenous matrices, K (the rate constant) depends on...

Back 49

1. Porosity
2. Tortuosity
3. Solubility of the drug in the release medium
4. Diffusion coefficent in the release medium

Front 50

How to you achieve constant release from matrix?

Back 50

1. Have a slow release device
2. Unique geometry
3. Specific non-uniform inital concentation
4. combined diffusion/erosion/swelling mechanism

Front 51

Define Graduments

Give examples

Polymers used

Back 51

Non-Erodible Matrix System

-inert, insoluble or nonerodible porous plastic disc

Ex: Desoxyn (methamphetamine)
Ex: Feosol (ferrous sulfate)

Polymers: Crospovidone & Camuaba wax

Front 52

Desoxyn

Back 52

Non-Erodible Matrix System

Gradument - inert, insoluble or nonerodible porous plastic disc

Methamphetamine

Front 53

Feosol

Back 53

Non-Erodible Matrix System

Gradument - inert, insoluble or nonerodible porous plastic disc

Ferrous sulfate

Front 54

Erosion Tablet

Back 54

Erodible Matrix System

Constant-T (theophylline)

Front 55

Constant-T

Back 55

Erodible Matrix System

Erosion Tablet
(theophylline)

Front 56

Uniphyl

Back 56

Erodible Matrix System

(theophylline & purdue)

Polymer: Cetostearyl alcohol

Front 57

LONTABS

Back 57

Erodible Matrix System

Foristal: Dimethidone maleate

Front 58

Procan SR tablets

Back 58

Erodible Matrix System

Procainamide HCl
Novartis

Front 59

SLOW-K

Back 59

Erodible Matrix System

Potassium

Front 60

K-TAB

Back 60

Erodible Matrix System

Potassium

Front 61

Name the 4 Specialized Diffusion-Controlled Systems

Back 61

1. Microporus Membrane-Coated Tablets
2. Solubility-Membrane Coated Tablets
3. Modified Enteric-Coated Tablets or Beads
4. pH-Independent Release System

Front 62

Explain

Microporous-Coated Tablets

Back 62

Diffusion-Controlled System

-tablet of the water-soluble drug is coated with an insoluble polymer (vinyl acetate) containing a small water soluble compound (common salt)
-polymer coating contains salt which dissolves leaving pours (microscopic) in the system.

Front 63

Explain

Solubility-Membrane Coated Tablets

Back 63

Diffusion-Controlled System

-tables of the drug are coated with a polymer containing a plasticizer which dissolves the drug before it is release.

plasticizer - dissolves drug before release

Front 64

Explain

Modified Enteric-Coated Tablets or Beads

Back 64

Diffusion-Controlled System

-Tablets are coated with two polymers
1. intestinal fluid insoluble polymer (Ethyl Cellulose)
2. intestinal fluid soluble polymer (Hydroxymethyl Cellulose Phthalate)

Front 65

Medrol Medules

Back 65

Modified Enteric-Coated beads

-beads in a capsule
Methylpredinosolone

Front 66

Explain

pH-independent release systems

Back 66

Diffusion-Controlled System

-Acidic or basic drugs are mixed with appropriate buffering agents before coating with a suitable polymer

{(drug + buffer)}coating/polymer

Front 67

Spansules capsules

Back 67

Encapsulated Dissolution Products

-Benzedrine (amphetamine sulfate)
-Ornade (Phenypropanolamine HCl & Chloropheniramine Maleate)

Front 68

Noyes-Whitney Equation

Back 68

Mechanism of Drug Release in Dissolution-Controlled Devices

D = Diffusion Coefficent
S = Surface area
h = thickness
V = volume of dissolution medium
Cs = Saturation solubility of the drug in the medium
Ct = Concentration of drug in medium at time t

Front 69

Hixon-Corwell Equation

Back 69

Mechanism of Drug Release in Dissolution-Controlled Devices

Wo and Wt are the inital weight and the weight of the drug remaining undissolved at time t
-Plot of (Wo - W) vs t is linear

**Surface area changes related to weight changes**

Front 70

Benzedrine

Back 70

Encapsulated Dissolution Product
[Spansules]

(amphetamine sulfate)
-beads with different coating thicknesses of the dissolving coat that surrounds the drug
**Different coating thicknesses**

Front 71

Ornade

Back 71

Encapsulated Dissolution Product
[Spansules]

(phenylpropanolamine HCl & Chlorpheniramine Maleate)
-beads with different coating thicknesses of the dissolving coat that surrounds the drug
**Different coating thicknesses**

Front 72

Contact Capsules

Back 72

Encapsulated Dissolution Product
[other encapsulated dissolution products]

-Phenylpropanolamine HCl
-Chlorpheniramine maleate
-atropine sulfate
-scopolamine HBr
-Hyoscyamine sulfate

Front 73

Methyl vinyl ether
&
Maleic anhydride

Back 73

Partly esterified copolymers in the Mechanism II of the bioerosion drugs (insoluble -> soluble)

Front 74

Polyactic acid

Back 74

polymer of the bioerodible system (Dissolves when system is implanted into the patient)

Front 75

Polyactic acid
Polyphosphoric acid
Polyglycolic acid
&
(Copolymers of these)

Back 75

Polymers of mechanism III of the bioerosion drugs (drug is entrapped in a polymer which undergoes hydrolytic or enzymatic cleavage)

Front 76

Osmotically Controlled system:

Mechanism of drug release (equation)

Back 76

dM/dt = rate of drug leaving the orifice
k' = membrane permeability coefficent
A = membrane area
h = membrane thickness
Delta Pi = osmotic pressure differences
delta P = hydrostatic pressure difference
Cs = concentration of drug in solution

Delta P & Cs are assumed to be neglegable

Front 77

Procardia X

Back 77

Osmotically Controlled System

(Nifedipine)
hypertesion

Front 78

Glucotrol XL

Back 78

Osmotically Controlled System

(Glipizide)
Type II diabetes

Front 79

Concerta

Back 79

Osmotically Controlled System

(Methylphenidate)
ADHD

Front 80

Tussionex suspension

Back 80

Ion-Exchange Principle

-Hydrocodone & Chlorpheniramine do ion-exchange complex with polystyrene resin

Front 81

Explain


Pennkinetic Drug Delivery System

Back 81

2nd generation Ion-exchange principle

-Polymer and Coating membrane: Provides Rate limiting step for the diffusion of ions going through

Front 82

Paul Ehrlich

Back 82

"Magic Bullet" term

Selective drug targeting to Physiological sites
-organs
-tissues
-cells
-sub-cellular organelles

Front 83

Targeted Drug Delivery

Passive Targeting vs. Active Targeting

Back 83

Passive (physicochemical interactions) [liposomes]
-Hydrophobic
-Electrostatic
-Mass

Active Targeting (Biological specific interactions)
-antigen-antibody
-ligand-receptor

Front 84

Epoietin
Epogen
Amgen

Back 84

Active targeted drug delivery (biological specific interactions)

Front 85

3 types of passive targeting drug veichles

Back 85

1. Liposome
2. Micelle
3. Nanopartical

Front 86

MLV
SUV
LUV

Back 86

MLV = multilamellar vessicles = liposomes
1000-5000 nm

SUV = smal unilamellar vesicles
-Sonication of MLV leads to production of SUV
-20-80 nm

LUV = Large unilamellar vesicles
-formed by evaporation under reduced pressure
-100-1000 nm

Front 87

How can you alter the permeability of liposomes

Back 87

-heat
-pH
-ionic strength
-additives (cholesterol)

Front 88

How do liposomes interact with cells

Back 88

1. Endocytosis
2. Fusion
3. Adsorption (contents diffuse through)

Front 89

Potential Advantages of Liosomes as a Drug Delivery System

Back 89

-Non-immunogenic
-Protect person from potential side effects / toxicity
-Protect cargo en route to target cell
-Deliver cargo to specific cell by using binding moiety

-target organell delivery of drug (pH changes from outside, inside and nucleous of cell)

Front 90

Doxorubicin HCl

Back 90

Liposome DDS

-MPEG steath liposome technology
-Drug in aqueous core
-30 minute infusion with 3 week washout period

Front 91

Nanoparticle matrix material

Back 91

-gelatin
-albumin
-polyactic acid
-polygalactic acid

Front 92

Critical micelle concentration

Back 92

-the at which the concentration amphiphilic molecules form micelles

Front 93

Advantages of Micelle

Back 93

Versatile carrier; small size (<100); evade phagocytic macrophages; increased circulation time, bioavailability; ease of formulation (good on paper); increased solubility of poorly soluble drugs (acts like surfactants); enhance penetration of drug through cell membrane;
Passive accumulation in regions of leaky vasculature; protection from possible inactivation' prevent undesirable side-effects of cytotoxic drugs

Front 94

Virosomes

Back 94

liposomes with viral proteins in their membranes

Front 95

Immunoliposomes

Back 95

liposomes with moieties such as
-carbohydrates
-hormones
-glycoproteins

moieties (functional group or part of a molecule)

Front 96

Things on "Active" liposome particles (5)

Back 96

1. Antibiotics
2. Carbohydrates
3. Peptides
4. Receptors
5. Oligonucleotides

Front 97

Herceptin

Back 97

Monoclonal antibody drugs

-breast cancer drug

Front 98

Methotrexate

Back 98

Drug linked to high molecular weight occuring substance
Albumin

Front 99

Dextran

Back 99

Drug linked to high molecular weight occuring substance

Polysaccharides
(daunomycin)

Front 100

Daunomycin

Back 100

Drug linked to high molecular weight occuring substance

Polysaccharides
(Dextran)

Front 101

Adriamycin

Back 101

Drug linked to high molecular weight occuring substance

DNA

Front 102

Albumin

Back 102

Drug linked to high molecular weight occuring substance

-Protein
-MW 69kDa
-widely distributed in the body

Front 103

Glycoproteins

Back 103

Drug linked to high molecular weight occuring substance

-Not specific, but may be modified to have site specificity

Front 104

Lipoproteins

Back 104

Drug linked to high molecular weight occuring substance

-Involved in lipid distribution

HDL 300-600 kDa
LDL 230kDa
VLDL 1 million Da
Chylomicrons 1 billion Da

Front 105

Ocusert

Back 105

Ocular Delivery System

(pilocarpine)
-two release rates: 20 or 40 mcg/hr
-reservoir system
-Titanium dioxide: visualization of device
-Membrane: EVA (ethylene-vinyl acetate copolymer)
-Plastasizer: 2-ethyl hexyl phthalate (improves membrane permeability to release pilocarpine)

Front 106

pilocarpine

Back 106

Ocular Delivery System

(Ocusert)
-two release rates: 20 or 40 mcg/hr
-reservoir system

-Titanium dioxide: visualization of device
-Membrane: EVA (ethylene-vinyl acetate copolymer)
-Plastasizer: 2-ethyl hexyl phthalate (improves membrane permeability to release pilocarpine)

Front 107

Progestasert

Back 107

Intravaginal system

-delivers progesterone to the intra-uterine region at a rate of 65 mcg/day for 1 year

Front 108

Tantum-T

Back 108

Intravaginal system

-copper wire wrapped around polypropylene base.
-copper is released by a combination of:
-chelation & ionization over 40 months

Front 109

CU-7

Back 109

Intravaginal system

-copper wire wrapped around polypropylene base.
-copper is released by a combination of:
-chelation & ionization over 40 months

Front 110

Polymers for Injections & Implants

Back 110

1. Hydrogels
2. Silicones
3. Biodegradable polymers
4. Titanium based devices

Front 111

Infusaid

Back 111

Implantable pump

-2 compartments: Drug & Propellant

-release drug independently of the drug's properties
-can release drug directly into blood
-can be refillable
-needs implantation