Formulation - Oral Controlled delivery Flashcards
What happens to solid oral dosage forms once they have entered the stomach?
Tablets/capsule
Aggregates or granules
Fine particles
Dissolution
Drug in solution
What biological factors affect oral bioavailability?
Includes both physiological factors and patient characteristics
- gastric emptying time
- intestinal transit time
- motility
- gastric contents
- food and feeding habits
- stability of drug in GI fluid
- other drugs
- pH
- drug metabolism
- PK profile
- drug efflux transporters
- gastrointestinal diseases
What does 100% bioavailability of a drug mean?
Complete release from dosage form
Fully dissolved in GI fluids
Stable in solution in GI fluids
Passes through GI barrier
Passes through liver unchanged
What factors affect bioavailability of compressed uncoated tablets?
Disintegration affect by nature of diluent, binder etc
Dissolution of a poorly soluble drug
- usually very limited
What factors affect bioavailability of coated tablets?
Film coating
- thickness and chemical nature of the coating
What is the aim of modified release oral dosage form?
Improved bioavailability
Designed to release drug slowly after ingestion leading to maintained blood levels
- avoids peaks and troughs
Improved patient compliance
- convenient
Night-time dosing
- can take in evening
Psychiatric patients
- don’t need to get up
Reduced side effects related to reduced peak plasma concentrations and reduced total dose
- aspirin
- aminophylline
Reduced irritancy from less ‘dose dumping’
More constant blood levels can bring improved efficacy
Economic savings
- can be expensive to have devices
More convenient form with the need for less frequent dosing
- repeat action systems designed to give patients two full doses
What are the problems with modified release oral dosage systems?
Physiological factors always variable
- precision affected
Gastro-intestinal transit time
Lodging of dosage form
- dose dumping
Not all drugs appropriate
- decreased half life drugs hazardous due to extreme dose-loading
Activity must be closely aligned to blood concentration
Tolerance
Physical size
Unit cost
How long does it take for a tablet to travel through the GI tract?
2.5 - 3 hours
- 50% of stomach contents emptied
4 - 5 hours
- total emptying of the stomach
2.5 - 3 hours
- 50% of emptying of the small intestine
30 - 40 hours
- transit through the colon
What is a sustained release tablet?
The release of a drug substance from a dosage form over an extended period of time
What is a controlled release tablet?
Dosage form that is able to provide some actual therapeutic control
- often a desire to achieve zero-order release
Give two types of controlled release tablets?
Temporal control
Spatial control
Why is achieving constant blood levels with controlled release very difficult?
Maintenance dose must be released in mass balance with drug elimination and at required therapeutic concentration
Physiological conditions often variation
Inter-patient variability in drug absorption
What do you need to know to achieve constant blood levels of drug?
Rate limiting step(s) for drug action
Optimal blood concentration curve
Elimination
- short half life
- furosemide (2 hours)
- deliver too much drug
- long half life
- phenytoin
- not desirable for CR products
How does metabolism affect drug concentrations in the blood?
Drugs that induce or inhibit metabolism are not suitable for CR formulations
Drugs that have a high first pass metabolism are also not suitable candidates
- overloading liver enzymes
Give examples of different types of modified release formulations
Enteric coated
Diffusion-controlled
Dissolution-controlled
Osmotically-controlled
