Modified release oral drug delivery Flashcards
Why modified release?
- Conventional dosage forms have little control over the delivery of drug, release rate is controlled
An ideal drug delivery system would deliver the drug to the site of action at a desired rate. TRUE OR FALSE?
TRUE
What is temporal control?
-Delivery drug at constant rate, where therapeutic effect is deirectly linked to steady state plasma concentration
What is spatial control?
- e.g Delivery to the colon or other sites in the GI tract
What is the rationale behind modified release systems?
-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
Drugs in which class are most suitable for modified release dosage forms?
Class 1
In order to improve bioavailability drugs in which class would benefit the most from formulation approaches to improve dissolution rate?
Class 2
What biological factors affect the product design and performance?
- Absorption rate constant
- Gastric emptying
- Transit time in small intestine
- Colonic tansit time
- pH and enzymes in the GI tract
What drug properties affect product design and performance?
- Aqueous solubility
- Partition coefficient logP
- Drug stability in the physiological environement
- Biological half life
To maintain a staedy state plasma concentration, the zero order release rate should be directly proportional to the elimination rate. TRUE OR FALSE?
TRUE
For drugs with short half life, the elimination rate is significant, therefore, require substantial sustaining supply e.g large sustaining dose. TRUE OR FALSE?
TRUE
What features do drugs not suitable for sustained release dosage forms have?
- 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
What are some fo the advantages for sustained release dosage forms?
- 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
What are the disadavantages of sustained release dosage forms?
- Potential overdosing due to unexpected dose dumping
- Not easy to adjust dose regimen
- More expensive per unit dose than conventional dosage forms
Hydrophilic polymers form a gel layer or viscous layer when in contact with water. TRUE OR FALSE?
TRUE
What two factors determine release rate in gel layer?
- Tortuosity
- Microviscosity
Give examples of matrix forming materials?
- HPMC
- Hydroxylpropyl cellulose
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?
TRUE
What are some ads of hydrophilic matrix systems?
- Simple
- Excipients are cheap and generally regarded as safe
- High drug load capacity
- No ghost matrix erodible
- Possible to obtain different profiles of release
What are some disads for hydrophilic matrix systems?
- Diffusion is dependent on two diffusion process
- Erosion makes drug release process complicated
- Formulation must be thouroughly studied with the right materials chosen
Describe the insoluble polymer matrix system?
- 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
In the insoluble polymer matrix system diffusion rate depends on what?
- Pore size
- Number of pores
- Tortuoisity
How can fast release insoluble polymers be achieved?
- Polymers with low molecular weight and low viscosity
- Low percentage of polymers in formulation
- Incorporation of release modifiers
How can slow release insoluble polymers be achieved?
- Viscus polymers
- Polymers with high molecular weight
- Polymers with high degree of crosslinking
- High percentage of polymers in formulation
What is membrane controlled systems?
-Dosage form covered in a membrane (monolithic form - one big unit or pellet form - many pellets )
Describe the osmotic pump system
- 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
What factors affect drug release in osmotic pump systems?
- 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
What is gastroretention?
-Helps etain drug in the stomach for longer against stomach emptying
What appraoches can be taken to achieve gastroretention?
- Mucoadhesion - mucoadhesive polymers such as chitosan
- Floating - gas generating agents or lipid can be used
- Size increasing system (after hydration)
In waht circumstances are drugs delivered to the colon?
- Inflammatory bowel disease e.g ulcerative colitis
- Carcinoma of colon
