2 - Oral Dosage Form Flashcards
What are some advantages to the oral dosage form?
- Effectiveness (systemic effects, onset/duration of action)
- Accuracy
- Convenience (noninvasive, product choice, compliance)
- Cost
What are some flaws of the oral dosage form?
- GI environment
- Bioavailability
- Drug targeting (drug will go anywhere once in solution)
- Emergency usage (onset too long)
- Pediatric/geriatric population
What is significant about the absorption in the stomach?
- First passing site
- Extreme pH
- Food/drink effect
- Short pass-over
- Limited absorption (about 20%)
What is significant about absorption in the small intestine?
- Primary site
- Milder environment
- Larger area
- Longer pass-over
- Major absorption
Does absorption occur in the large intestine?
Minimal
Does absorption occur in the esophagus?
No
Does absorption occur in the mouth?
Buccal and sublingual absorption
Does absorption occur in the rectum?
Yes
What are some components required to make an oral capsule/tablet work?
- Absorption (solubility, permeability, safety)
- Stability (physical, chemical, biological, pharmacological)
- Processing (compatibility, compressibility, stability, feasibility)
What should be done if a drug doesn’t have good stability in the GI tract?
Use a different dosage form
What is required for a drug to be considered stable?
Overall adequate stability to environmental factors like temp, light, moisture (in vitro); various pH values, enzymes, and possible first-pass metabolism (In vivo)
Why is entrophen enteric-coated?
So it will not be absorbed in the stomach, b/c it is known to cause ulcers
What are ways to increase solubility?
- Different salt forms
- Particle micronization
- Processing modification
- Faster disintegration/dissolution
- Formulating solutions
- Surfactant application
What is a disadvantage to particle size micronization?
Increased solubility, but particles that are too small will stick together and cause processing problems
What can be done in vitro to increase stability?
- Coating
- Additive application (ex: antioxidants, preservatives)
- Protective packaging (ex: amber glass, inert gas replacement)
What can be done in vivo to increase stability?
- Coating
- Controlled/sustained release
- Site-specific release
What can be done to bypass absorption limitation?
- Improve solubility and stability
- Select appropriate excipients
- Increase disintegration and dissolution
- Modify drug release profiles
- Use administration strategies
What can be done to prevent drug metabolism before absorption?
- Structural modifications
- Preparation coating
- Controlled release
What can be done to prevent drug metabolism after absorption?
Prodrug
What should be considered when metabolism is a problem?
- Appropriate formulation
- Dose increase (pay attention to toxicity)
- Prodrugs
- Enzyme inhibitors
- Other administration routes (ex: rectal, sublingual, parenteral)
What can be used to retain formulations in the stomach or portions of small intestine?
Adhesive polymers
Is it possible to target oral drugs outside of the GI tract?
No
What can be used for drug targeting?
- Mucoadhesive polymers
- Hydrophilic gels
What should be considered when planning to target a drug?
- Prolonged residence time
- Increased contact w/ membrane
- Localization in specific regions
- Improved bioavailability
What is very important w/ respect to oral solutions?
Taste and color
Which dosage forms can have quick-dissolving properties?
- Oral
- Buccal
- Sublingual
Is there any PK/PD changes in quick-dissolving drugs?
No
Which types of drugs are suitable to be quick-dissolving?
- Analgesics
- Antihistamines
- Cough/cold
- Migraine
- Antidepressants
- Anti-psychotics
- Parkinson’s
What are the different types of quick-dissolving dosage forms?
- Oral disintegrating tablets
- Fast-melt tablets
- Quick-dissolving tablets
- Mouth-dissolving tablets
- Orodispersible tablets
- Flashtab
What are some common excipients used in quick-dissolving compounds?
- Mannitol and sorbitol
- Crospovidone, sodium starch glycolate, croscarmellose
- Combination w/ effervescent ingredients (calcium bicarbonate)
What can be done to mask the taste of a drug?
- Additive dilution
- Film coating of particles/granules
- Melting w/ lipid-based excipients
- Cyclodextrin encapsulation
- Wet granulation
What should taste-masking NOT affect?
Drug properties and in vivo profiles
Why would a drug need to have a controlled release?
- Fewer administration frequency
- Steady blood concentration
- Better therapeutic outcome
- Improved px compliance
What is the definition of controlled release?
- Modified drug release rate
- Extended period of drug release
- Controlled drug direction to site
Controlled release drugs have better ____ therapeutic outcomes
In vivo
What is the difference between sustained release and controlled release?
- Sustained release = any dosage form that provides medication over an extended period of time
- Controlled release = system is able to provide some actual therapeutic control
What should be some characteristics of the ideal controlled release preparation?
Should be able to provide an exact amount of drug at the site of action for a precise period of time (zero-order drug release)
Most controlled release or sustained release tablets release drug contents in ______ or _____ kinetics
First-order or pseudo zero-order kinetics
Most delayed release dosage forms are for ___ drug delivery
Oral
For controlled release, release of drug is independent of _____
External factors or environment
Are controlled release dosage forms only for oral drug delivery?
No, various administration routes
Targeted release is generally for _____ drug delivery
Parenteral
Do controlled release drugs have improved therapeutic outcomes? Why or why not?
Yes b/c they reduce drug concentration fluctuations and optimize drug bioavailability
Do controlled release drugs generally increase or decrease patient compliance?
Increase
What are some disadvantages to controlled release dosage forms?
- “Dose-dumping” dangers
- Difficult dosing termination
- Possible erratic or variable absorption due to GI interactions
- Complex production and quality control procedures
- Higher unit cost
Which diseases are controlled release dosage forms appropriate for?
- Chronic conditions and long-term administration regimens
- Ex: CV (hypertension, heart diseases); respiratory (asthma, allergy); others (depression, mood control)
When should controlled release dosage forms NOT be used?
For short-term uses (less than 2 weeks, antibiotics, analgesics)
What is a suitable half life range for a controlled release dosage form? What would a half life out of this range cause?
- 2-8 hours
- Too short = higher drug dose
- Too long = no need for controlled release
What is a suitable GI tract passage time for a controlled release dosage form and why?
8-12 hours b/c limited absorption after small intestine
For a controlled release dosage form, should absorption rate or drug release rate be faster?
Absorption rate
Can controlled release drugs be chewed or crushed?
No, never
What is the preferred dosing range for a controlled release drug and why?
- Preferred less than 0.5 g, but can be 0.5-1 g
- Less than 500 mg is more suitable for controlled release b/c unit dose may be increased in order to accommodate administration frequency
What are some stability requirements for a controlled release dosage form?
- Wide pH range (1-8)
- No acid-base hydrolysis
- No enzymatic cleavage
- No potential drug/drug or drug/food interactions
What are the various types of drug release mechanisms?
- Diffusion controlled (reservoir and matrix)
- Dissolution/diffusion controlled
- Dissolution controlled (reservoir and matrix)
- Osmotic pressure controlled
Does diffusion or dissolution play more of a significant role in drug release?
Dissolution
What is involved in a diffusion controlled reservoir system?
- Drug core surrounded by insoluble polymeric film
- Nature of polymer film determines rate of drug release from system
What are some characteristics of a diffusion controlled reservoir system?
- Zero-order delivery possible
- Difficult to deliver large molecules
- Potential toxicity if failed in vivo
- Physically removed from site
What does Fick’s law describe?
Process of drug movement across the membrane
What are the 2 types of matrix systems?
Soluble and insoluble
What does a diffusion controlled matrix system include?
- Drug-polymer mixture (drug dispersed homogeneously through polymer)
- Insoluble matrix
- Release rate controlled by polymer
What are some characteristics of a diffusion controlled matrix system?
- Easy to manufacture
- Many polymer choices
- Possible to deliver large molecules
- Zero-order delivery impossible
- Removal of matrix necessary if implanted
What does a bioerodible system contain?
- Drug-polymer mixture (drug dispersed homogeneously in chemical polymers)
- Soluble matrix
- Release rate controlled by polymer
- Diffusion and dissolution type
What are some characteristics of bioerodible systems?
- Easy to manufacture
- Many polymer choices
- Possible to deliver large molecules
- Difficult to control release rate due to both dissolution and diffusion
- Potential problem w/ degraded polymers in vivo
- Will change physical configuration over dissolution period
What does a dissolution system include?
- Reservoir or matrix
- Release rate controlled by drug, polymer, or combinations
What does making a dissolution system involve?
- Selecting appropriate salts or derivatives w/ lower aqueous solubility
- Coating drug w/ slowly dissolving material
- Incorporating substance into tablet made of slowly dissolving carrier
What are some characteristics of a dissolution system?
- Different choices for formulations
- Possible to deliver large molecules
- Release rate dependent on many parameters
- Complex release mechanisms
How does a dissolution system maintain drug concentrations?
- Beads w/ thinnest coating will provide the initial dose
- Beads w/ thicker coatings can maintain necessary drug concentrations at later durations
What does an osmotic pump involve?
- Drug core w/ osmotic-producing agent
- Semipermeable membrane
- Release rate controlled by osmotic pressure
What are some characteristics of an osmotic pump?
- Zero-order release achievable
- One model fits all drugs (theoretical); as long as no compatibility issues btwn drugs
- Drug release independent of environment
- Higher production cost due to special equipment and stringent quality controls
What determines the drug release rate of an osmotic pump?
Water flowing rate into the device and drug concentration w/in the device
Which drug release mechanisms are used for tableting?
- Matrix (uncoated)
- Tablet cores (for further coating)
Which drug release mechanisms are used for fluid-bed technology?
- Pellets for capsules/tablets
- Reservoir
Which drug release mechanisms are used for film coating?
- Reservoir
- Osmotic pumps
- Enteric-dissolved
What is tested during quality control?
- Drug content
- Drug content uniformity
- Drug disintegration (required for enteric-coated formulations; not needed for most controlled release formulations)
- Drug dissolution (in different mediums like gastric fluid, intestinal fluid, water)
What is required for a drug to pass dissolution testing?
Over 85% drug release w/in 8 hours
What is coming in the future w/ regards to oral dosage form?
- More controlled release products
- Protein and peptide formulation
- Improvement in bioavailability and drug targeting
- More biodegradable polymers
