Properties and composition of formulation

Question 1

Drug Formulation Design considerations

Answer 1

-properties of drug
-properties and composition of formulation
-biological factors influencing performance (ADME and toxicity, ADMET)
-must be properly balanced to reach clinic

Question 2

Formulation factors affecting absorption

Answer 2

-dosage form design
-rates of drug release
-times spent at absorption site

Question 3

Dosage form design factors

Answer 3

-size, excipient, compositions
-manufacturing parameters

Question 4

Rates of drug release factors

Answer 4

-disintegration, dissolution, deaggregation, erosion of coatings, osmotic pumps, etc

Question 5

Time at absorption site factor

Answer 5

-mucoadhesives, coatings

Question 6

Types of solid dosage forms

Answer 6

-tablets
-capsules
-film strips
-powders
-granules, beads
-minitabs
-osmotic pumps
-gelcaps
-other

Question 7

Anatomy of a Tablet

Answer 7

-Coating
-Ingredients: active, diluent, binder, disintegrant, glidant, lubricant

Question 8

Excipients

Answer 8

-inert substance that forms vehicle for drug
-gum arabic, starch
-not actually inert tho, warning on HIV drug excipient

Question 9

Excipient classification (13 classes)

Answer 9

Binders
Disintegrants
Fillers
Lubricants
Glidants
Compression Aids
Colors
Sweeteners
Preservatives
Dispersing agents
Film Formers
Flavors
Printing Inks

Question 10

Common excipients

Answer 10

-Cellulose based
-sugars
-starch
-synthetic polymers
-inorganic
-others

Question 11

Cellulose based excipients

Answer 11

-microcrystalline cellulose (MCC), SMCC, HPMC, HPC, ethylcellulose

Question 12

Sugar excipients

Answer 12

sucrose, lactose, mannitol

Question 13

starch excipients

Answer 13

pregelatinized starch, sodium starch glycolate

Question 14

synthetic polymer excipients

Answer 14

-polyvinyl pyrrolidone (PVP)
-polyethylene oxide (PEO)

Question 15

inorganic excipients

Answer 15

-dicalcium phosphate
-silicon dioxide

Question 16

other excipients

Answer 16

-magnesium stearate
-stearic acid
-crospovidone
-talc
-shellac
-titanium dioxide
-gelatin

Question 17

Excipient use

Answer 17

-compendial (lactose, mannitol)
-GRAS (only applies to food additives)
-food additive peteition
-application through new drug application

Question 18

Critical factors in excipient selection

Answer 18

-origin
-functional category
-quality and purity
-impurity levels and extent of characterization
-batch-to-batch consistency
-stability
-compatibility
-toxology
-cost
-activity
-patent status

Question 19

Ingredients affecting bioavailability, stability, marketing

Answer 19

-disintegrants: enhance rate
-coatings: control release
-flavors: mask taste
-colors: recognition
-misc

Question 20

Excipient compatibility testing

Answer 20

-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

Question 21

Flow properties: Angle of Repose

Answer 21

-excipients can control flow-glidants
-better flow = better mixing and filling of tablet machines
-helps keep dose the same

Question 22

Angle of Repose

Answer 22

-characteristic of how well a powder flows
-smaller angles = increased flow

Question 23

Blending

Answer 23

-important for assuring content uniformity in larger batches

Question 24

Small scale blending

Answer 24

-trituration: mortar and pestle mixing
-spatulation: mixing with spatula

Question 25

Larger scale blending

Answer 25

-sifting
-tumbling

Question 26

Content uniformity

Answer 26

-assuring all tablets contain same weight and content
-complete mixing

Question 27

Ingredients that affect compaction

Answer 27

-diluents/fillers: add mass
-binders/adhesives: hold tablets together
-lubricants: reduce friction in tablet presses
-antiadherents: no sticking
-glidants: enhance flow

Question 28

Single Punch Press-tableting

Answer 28

Slide 63 machine

Question 29

Basic compressing unit

Answer 29

upper punch, 2 die, lower punch

Question 30

Organoleptic senses to consider when coating/binding treatments

Answer 30

Sight: size, shape, color, markings
-smell
-sound: rattling?
-taste
-touch: coatings, isotonicity, viscocity

Question 31

Effect of compression force on powder (flow)

Answer 31

Initially –> repacking (push down) –> deformation –> decompressing: elastic vs plastic

Question 32

Solid Dosage form requirements

Answer 32

-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)

Question 33

Content uniformity factors

Answer 33

-mixing and powder flow
-glidants
-excipient concentrations should also be tight

Question 34

Shelf stability for 2 years

Answer 34

-excipient compatibility is big
-solvents may increase degradation

Question 35

Reproducible release metrics

Answer 35

-measured by dissolution for batch release
-disintegrants can be used that swell in water
-excipients to control release