Modified release oral drug delivery

Question 1

Why modified release?

Answer 1

• Conventional dosage forms have little control over the delivery of drug, release rate is controlled

Question 2

An ideal drug delivery system would deliver the drug to the site of action at a desired rate. TRUE OR FALSE?

Answer 2

TRUE

Question 3

What is temporal control?

Answer 3

-Delivery drug at constant rate, where therapeutic effect is deirectly linked to steady state plasma concentration

Question 4

What is spatial control?

Answer 4

• e.g Delivery to the colon or other sites in the GI tract

Question 5

What is the rationale behind modified release systems?

Answer 5

-The basic idea is to alter the pharmacokinetic profile of a drug using delivery dosage forms, so that the PK profile is more of a property of the delivery systems and not solely the inherent property of the drug molecule irself

Question 6

Drugs in which class are most suitable for modified release dosage forms?

Answer 6

Class 1

Question 7

In order to improve bioavailability drugs in which class would benefit the most from formulation approaches to improve dissolution rate?

Answer 7

Class 2

Question 8

What biological factors affect the product design and performance?

Answer 8

• Absorption rate constant
• Gastric emptying
• Transit time in small intestine
• Colonic tansit time
• pH and enzymes in the GI tract

Question 9

What drug properties affect product design and performance?

Answer 9

• Aqueous solubility
• Partition coefficient logP
• Drug stability in the physiological environement
• Biological half life

Question 10

To maintain a staedy state plasma concentration, the zero order release rate should be directly proportional to the elimination rate. TRUE OR FALSE?

Answer 10

TRUE

Question 11

For drugs with short half life, the elimination rate is significant, therefore, require substantial sustaining supply e.g large sustaining dose. TRUE OR FALSE?

Answer 11

TRUE

Question 12

What features do drugs not suitable for sustained release dosage forms have?

Answer 12

• Half life too long or too short
• Poor safety margin
• Large dose
• Poor solubility
• Absorption rate is too slow
• Not uniformily absorbed through out the GI tract

Question 13

What are some fo the advantages for sustained release dosage forms?

Answer 13

• Reduced dosing frequency
• Improved patient compliance
• Reduced fluctuantion in plasma concentration
• Reduced side effects due to high peak conc
• Improved action of drug during night time
• Reduction in GI irritation caused by dose dumping

Question 14

What are the disadavantages of sustained release dosage forms?

Answer 14

• Potential overdosing due to unexpected dose dumping
• Not easy to adjust dose regimen
• More expensive per unit dose than conventional dosage forms

Question 15

Hydrophilic polymers form a gel layer or viscous layer when in contact with water. TRUE OR FALSE?

Answer 15

TRUE

Question 16

What two factors determine release rate in gel layer?

Answer 16

• Tortuosity

- Microviscosity

Question 17

Give examples of matrix forming materials?

Answer 17

• HPMC

- Hydroxylpropyl cellulose

Question 18

Gel modifiers such as sugars and soluble polymers can modify
-drug release
-rates and extent of the hydration process
-microenvironment in the gel layer
TRUE OR FALSE?

Answer 18

TRUE

Question 19

What are some ads of hydrophilic matrix systems?

Answer 19

• Simple
• Excipients are cheap and generally regarded as safe
• High drug load capacity
• No ghost matrix erodible
• Possible to obtain different profiles of release

Question 20

What are some disads for hydrophilic matrix systems?

Answer 20

• Diffusion is dependent on two diffusion process
• Erosion makes drug release process complicated
• Formulation must be thouroughly studied with the right materials chosen

Question 21

Describe the insoluble polymer matrix system?

Answer 21

• Less frequently used
• Polymers for a matrix in which drug particles are interspersed
• The polymer matrix remains intact throughout the GI tract
• Drug molecules diffuse out through the various channels

Question 22

In the insoluble polymer matrix system diffusion rate depends on what?

Answer 22

• Pore size
• Number of pores
• Tortuoisity

Question 23

How can fast release insoluble polymers be achieved?

Answer 23

• Polymers with low molecular weight and low viscosity
• Low percentage of polymers in formulation
• Incorporation of release modifiers

Question 24

How can slow release insoluble polymers be achieved?

Answer 24

• Viscus polymers
• Polymers with high molecular weight
• Polymers with high degree of crosslinking
• High percentage of polymers in formulation

Question 25

What is membrane controlled systems?

Answer 25

-Dosage form covered in a membrane (monolithic form - one big unit or pellet form - many pellets )

Question 26

Describe the osmotic pump system

Answer 26

- Only water molecules diffuse through the membrane - Solid contents dissolve and build up osmotic pressure inside - Water molecules enter the core due to the difference of osmotic pressure - Drug solution pushed out via the orifice and more solid content dissolve

Question 27

What factors affect drug release in osmotic pump systems?

Answer 27

- Type of semipermeable membranes (different membranes may have different k) - Area and thickness of the semipermeable membrane - Solubility of drug - Osmotic pressure - Size of orifice which affects the difference of static pressure

Question 28

What is gastroretention?

Answer 28

-Helps etain drug in the stomach for longer against stomach emptying

Question 29

What appraoches can be taken to achieve gastroretention?

Answer 29

- Mucoadhesion - mucoadhesive polymers such as chitosan - Floating - gas generating agents or lipid can be used - Size increasing system (after hydration)

Question 30

In waht circumstances are drugs delivered to the colon?

Answer 30

- Inflammatory bowel disease e.g ulcerative colitis | - Carcinoma of colon