Properties and composition of formulation Flashcards
Drug Formulation Design considerations
-properties of drug
-properties and composition of formulation
-biological factors influencing performance (ADME and toxicity, ADMET)
-must be properly balanced to reach clinic
Formulation factors affecting absorption
-dosage form design
-rates of drug release
-times spent at absorption site
Dosage form design factors
-size, excipient, compositions
-manufacturing parameters
Rates of drug release factors
-disintegration, dissolution, deaggregation, erosion of coatings, osmotic pumps, etc
Time at absorption site factor
-mucoadhesives, coatings
Types of solid dosage forms
-tablets
-capsules
-film strips
-powders
-granules, beads
-minitabs
-osmotic pumps
-gelcaps
-other
Anatomy of a Tablet
-Coating
-Ingredients: active, diluent, binder, disintegrant, glidant, lubricant
Excipients
-inert substance that forms vehicle for drug
-gum arabic, starch
-not actually inert tho, warning on HIV drug excipient
Excipient classification (13 classes)
Binders
Disintegrants
Fillers
Lubricants
Glidants
Compression Aids
Colors
Sweeteners
Preservatives
Dispersing agents
Film Formers
Flavors
Printing Inks
Common excipients
-Cellulose based
-sugars
-starch
-synthetic polymers
-inorganic
-others
Cellulose based excipients
-microcrystalline cellulose (MCC), SMCC, HPMC, HPC, ethylcellulose
Sugar excipients
sucrose, lactose, mannitol
starch excipients
pregelatinized starch, sodium starch glycolate
synthetic polymer excipients
-polyvinyl pyrrolidone (PVP)
-polyethylene oxide (PEO)
inorganic excipients
-dicalcium phosphate
-silicon dioxide
other excipients
-magnesium stearate
-stearic acid
-crospovidone
-talc
-shellac
-titanium dioxide
-gelatin
Excipient use
-compendial (lactose, mannitol)
-GRAS (only applies to food additives)
-food additive peteition
-application through new drug application
Critical factors in excipient selection
-origin
-functional category
-quality and purity
-impurity levels and extent of characterization
-batch-to-batch consistency
-stability
-compatibility
-toxology
-cost
-activity
-patent status
Ingredients affecting bioavailability, stability, marketing
-disintegrants: enhance rate
-coatings: control release
-flavors: mask taste
-colors: recognition
-misc
Excipient compatibility testing
-binary or formulation blends (w/ or w/o 10-20% water)
-suspension with drug
-mechanical stress by milling drug
-using amorphous drug
-compacts of prototype formulation by direct compression
-tablets processed by wet granulation
-calorimentry
Flow properties: Angle of Repose
-excipients can control flow-glidants
-better flow = better mixing and filling of tablet machines
-helps keep dose the same
Angle of Repose
-characteristic of how well a powder flows
-smaller angles = increased flow
Blending
-important for assuring content uniformity in larger batches
Small scale blending
-trituration: mortar and pestle mixing
-spatulation: mixing with spatula
Larger scale blending
-sifting
-tumbling
Content uniformity
-assuring all tablets contain same weight and content
-complete mixing
Ingredients that affect compaction
-diluents/fillers: add mass
-binders/adhesives: hold tablets together
-lubricants: reduce friction in tablet presses
-antiadherents: no sticking
-glidants: enhance flow
Single Punch Press-tableting
Slide 63 machine
Basic compressing unit
upper punch, 2 die, lower punch
Organoleptic senses to consider when coating/binding treatments
Sight: size, shape, color, markings
-smell
-sound: rattling?
-taste
-touch: coatings, isotonicity, viscocity
Effect of compression force on powder (flow)
Initially –> repacking (push down) –> deformation –> decompressing: elastic vs plastic
Solid Dosage form requirements
-content uniformity (85-115% API)
-good organoleptic properties for patients (colors, taste, compliance issues)
-shelf stable for 2 years
-Reproducible release metrics
-Must not be friable (breakable)(binders and coatings)
Content uniformity factors
-mixing and powder flow
-glidants
-excipient concentrations should also be tight
Shelf stability for 2 years
-excipient compatibility is big
-solvents may increase degradation
Reproducible release metrics
-measured by dissolution for batch release
-disintegrants can be used that swell in water
-excipients to control release
