Lecture 13 (Cut off for Exam 3) Flashcards
Tablets
Unique Appearances of Tablets
- Used to identify product and reduce errors
- Size, shape, weight, hardness, thickness, labeling, scoring, coating, disintegration and/or dissolution characteristics all give tablets their unique appearances
What process do solid forms go through to become small aggregates?
Disintegration
What process do solid forms or small aggregates go through to enter solution?
Dissolution
Do drugs need to be in solution to be absorbed?
Yes.
Tablet Categories (7)
- Compressed tablets
- Multiple compressed tablets
- Buccal and sublingual tablets
- Fast-dissolving or dispersing tablets
- Coated tablets (sugar, DR, sustained action)
- Administration by other routes: vaginal
- Used to prepare solutions - effervescent, dispersing, tablet titurates
Tablet Advantages (9)
- Easy to administer
- More stable than liquids
- Convenient for patient
- Economical
- Can control release of API
- Tamper resistant
- Can adjust dose
- Easy to identify
- More accurate dose
Tablet Disadvantages (6)
- Taste and odor
- Hard to swallow
- May be mistaken as candy
- Slower onset of action than liquids (esp. solutions)
- Can’t administer to everyone
- Powder flow homogeneity and compaction
Physiochemical Properties of API in Tablets
- Compaction and flow properties
- Salt form
- Polymorphic form
- Melting point
- Purity of active
- Stability/interaction with excipients
- Particle size - affects segregation and dissolution
Diluents/Fillers
-Used to bulk up mixture
-Used with potent drugs (low doses)
-Should have good compaction properties
-Ideally good flow as well
EX: Lactose and microcrystalline cellulose
Binders
-Promote adhesion of powder particles
-Important for tablet hardness and friability
-Two ways to incorporate: dry (direct compression) and liquid state (wet granulation)
EX: Starch and PVP
Disintegrating Agents
-Promote tablet disintegration in fluids
-Ideally AFTER swallowing
-Mechanism: absorbs water and swells
-Concentration affects rate of disintegration
-Can be induced multiple ways: intragranulation (in granules), extragranulation (blended with granules), and in powder blend
EX: Starch and starch derrivatives
Lubricants
-Prevent formulation/tablet sticking to machinery
-Blending times = critical
EX: Magnesium stearate and Talc
Overblending of Lubricant
- Creates hydrophobic surfaces
- Causes weaker tablet compacts
- Causes slower dissolution
Glidants
-Improve flowability of powders
-Powder flow = critical during tableting (must flow freely to fill dye cavities during process)
-Flowability measured by angle of repose (smaller the angle, better the flow)
EX: Silica derivative (Cab-O-Sil) and Talc
Dyes
- Used to make color variants on market
- FD&C dyes = water soluble colors
- FD&C lakes = insoluble aluminum dyes
- Iron oxides
- Some colorants block light as well (opacifiers)
Flavors & Sweetners
- “Mask” taste/odor of drugs or excipients
- Spray dried and other flavors
- Natural and artificial sweetners
Machinery Used to Make Tablets
- Single Station Tablet Press - punches and dies single tablet at a time
- Mutli-Station Tablet Press - punches and dies multiple tablets at a time
What gives tablets their unique shapes and appearances?
Punches and dies. They dictate shape, size, and surface of tablet
Tablet Production Methods (4)
- Direct compression
- Wet granulation - manually or by fluid bed
- Dry Granulation (roller compaction)
- Other methods - Ink-jet printing, hot melt extrusion
Direct Compression
-Requires powders to be free-flowing and compressible
Steps:
- Size drugs with sieves
- Weigh specific amounts of API/excipients
- Blend ingredients well (add lubricants AFTERWARDS)
- Compress into tablets
Direct Compression Problems (4)
- Content uniformity in low dose drugs
- Compressibility of high-dose drugs
- Segregation in hopper is possible
- Blending of lubricant is CRITICAL
Wet Granulation
Blended Powders»_space; [Wet Granulation]»_space; Granules»_space; [Compressed]»_space; Tablets
-Can improve compressibility, flowability and content uniformity of powder blend
Wet Granulation Steps
- Size, weigh and blend with excipients
- Add liquid binder to slowly dampen
- Screen damp mass
- Dry and size/sieve (must be done before tableting)
- Add lubricant and blend
- Compress into tablets
Liquid Binders
- Cause powdered particles to adhere and form damp mass
- Binding agents = PVP (or other)
- Liquid can be aqueous or organic
- Potential problems = over and underwetting
Fluidized Bed Granulator
- Used for making granules
- Air flow causes continual movement (like popcorn toy for children)
- More efficient drying
- Can use apparatus to wet, granulate, and dry mixture
Are there stability issues connected with Wet Granulation?
Possibly, due to the heat and water.
Dry Granulation
- Roller Compression
- Alternative method to direct compression
- No water or heat required (advantage!)
Dry Granulation Disadvantages
- Active and/or diluent powders must have cohesive properties
- Granules are formed ONLY when those properties are present, other will only have powders
Ink-jet Printing
- New technology
- Makes tablets with specific architectures
Properties of Good Tablets (5)
- Physical stability - remains as whole drug during dispensing, manufacturing, and transport
- Chemical Stability - amount of drug present as labels, beyond expiration date
- Esthetic Appearence - free of chips/cracks, contamination, and uneven coloring
- Bioavailability
- Weight and content uniformity - varies from source to source (different manufacturers
Problems in Tabletting (6)
- Capping
- Improper fill
- Picky or sticky
- Crumbling
- Mottled Tablets
- Non-releasing tablets
Capping
- When top of tablet separates or laminates after compression
- Usually from trapped air - lowered compression force from induced die feeders
In-Vitro Tests of Finished Tablets (7)
- Content Uniformity
- Weight uniformity
- Tablet density/diameter
- Hardness
- Friability
- Disintegration
- Dissolution
Hardness
- Amount of force needed to break tablet
- Tablet hardness tester tests for this
Friability
- Friabilator tests this
- Tendency of tablet to crumble (weight loss in shipping)
Disintegration
- USP disintegration tests
- Tests for time of disintegration in various fluids (37C)
- Tests in water, simulated gastric fluid, simulated intestinal fluid, and specialized buffer fluid
Dissolution
- Utilize paddle or basket apparatus most commonly
- Take out sample at specific times and test to determine concentration via UV spectrometer or HPLC
- Other methods are used as well like reciprocating cylinder (III), flow-through (IV), and others for various delivery systems
Factors Affecting Disintegreation
- Addition of disintegrants
- Manufacturing methods - wet or direct
- Pressure used for compression
- Tablet Hardness
Q-Value
- Percent of dose that should be dissolved at a specific time (at least __% withing __mins dissolves)
- 6+6+12 tablets tested until specifications are met
- Similar procedure for capsules
- Multiple Q-values for ER products with many time points
- For enteric, slightly different procedure utilized
Factors Affecting Dissolution
- Particle Size of drug
- Solubility of drug in solvent
- pH of solvent
- Temperature of media
- Rate of mixing
- Excipients in formulation
Multiple Compressed Tablets
- Several reasons for multiple compression tablets
- Separates incompatible compartments
- Make each layer release at a different rate
- Unique marketing
Chewable Tablets
- Designed to be chewed
- Good for people who have difficulty swallowing
- Softer than regular tablets
- Critical considerations for formulations are organoleptic properties and selections of diluents, flavors, and colors
Organoleptic Properties
- Taste
- Flavor
- Aftertaste
- Mouthfeel
- Toothpacking
Oro-Dissolving or Dispersing Tablets
- Designed to disintegrate or dissolve in mouth
- Good for people with difficulty swallowing
- Disadvantages = weak, moisture sensitive, organoleptic properties must be considered
- Various manufacturing methods
Other Tablet Types (2)
- Buccal - designed to slowly dissolve and can be systemic or local
- Sublingual - dissolves rapidly, rapid absorption and onset (nitroglycerin)
- Both small and flat
- Avoids gastric fluids and first pass metabolism
Vaginal Tablets
- Large and flat - tend to be oval or elliptical
- Dispensed with applicator
- Used to deliver anti-infection agents or homones
Effervescent Tablest
- Contain excipients that react with water to make CO2
- Acid-base reaction (acids = citric acid and tartanic acid, salt = sodium bicarbonate)
- Few other excipients required - binders (low concentration of PVP), lubricants, flavors/sweeteners
Effervescent Tablet Pros and Cons
Pros
- Rapid dissolution
- Carbon dioxide can help mask the taste to an extent
Cons
- Special production facilities
- Packed in hermetically sealed containers
- More expensive
- Increased sodium concentrations
Pills
Solid dosage forms compounded by pharmacist.
-Damp mass rolled into pill tile or filled into molds
Problems with Compounding Pills
- Lack of physical/chemical characterizations of components
- Lack of processing controls
- No control of disintegration
Proper Packaging/Storage
- Important to maintain stability
- Tablets and capsules should be in tightly sealed container and a cool, dry place (like a potato!!)
- Bulk packaging usually contains desiccants to absorb moisture
- Photolytic drugs are packaged in opaque containers to protect from light
Protecting Drugs After Dispensing
- Usually packaged in amber vials to help maintain stability
- Nitroglycerin is an example of an exception. Must be kept in its ORIGINAL container
Proper Administration
- Important to obtain therapeutic benefit
- Take tablets with a glass of water to allow for easier swallowing and to minimize esophageal sticking
- Rule of thumb is 8 oz of water
- If they have reflux, recommend that the patient takes the medication at least an hour before lying down
- Number of tricks to swallow tablets/capsules easier
