Tablet Manufacturing and Evaluation

tablet

a mixture of active substances (drug) and excipients in powder, granule, or crystalline form, pressed or compacted into a solid

advantages

tablet ____________:

-convenient, portable, simple

-accurate dose

-stable

-taste masking

-drug release flexibility (controlled release and sustained release)

-target site can be oral cavity, vaginal, effervescent

disadvantages

tablet ______________:

-degredation through the GIT and first pass metabolism

-systemic distribution has side effects with large doses

-swallowing difficulty

molded, compressed

two types of tablets: ____________ and _____________

compressed

__________________ tablets can be immediate release, multiple compressed, sugar coated, film coated, gelatin coated, enteric coated, buccal/sublingual, chewable, effervescent, lozenge, melt extrusion, or delayed/extended/controlled release

enteric

__________ coated tablets are designed to dissolve at the basic pH of the intestines, allowing it to stay intact through the stomach

effervescent

______________ tablets haves high salt content, so they are not recommended for patients with hypertension

contain sodium bicarbonate, tartaric, and citric acids that produce CO2 with water

excipients

largely inert substances that is added to a drug to improve administration or absorption

filler (diluent)

lactose monohydrate - be cautious if lactose intolerant

binder

polymer ot form granules and help tablet compaction

Ex: povidone (PVP), HPC, PEG

4-6%

percent composition of binders in tablets

lubricant

reduces adhesion to tooling or other tablet processing (punching machine)

Ex: magnesium stearate, talc

0.5-1%

percent composition of lubricant in tablets

glidant

improves the flow properties of tablets; added before compression

Ex: colloidal silicon dioxide, talc

<2%

percent composition of glidant in tablets

disintegrant

swells in water to help with disintegration

Ex: starch 1-5%

3-6%

percent composition of disintegrant in tablets

superdisintegrants

speeds up disintegration and dissolution (2-4%)

Ex: sodium starch glycolate, croscarmellose sodium, crospovidone, carbon dioxide

compression enhancer

improves compaction

Ex: microcrystalline cellulose

15-25%

percent composition of compression enhancers in tablet

<1%

percent composition of colorant, flavor, and sweetener in tablet

wet granulation

process in which a liquid (hydroalcoholic) is added to the powder with agitation to produce agglomeration or granules when dried which are sieved and compressed into a tablet

lubricant

excipient that is added last just before the tablet is compressed

dry granulation

similar process as wet granulation except no hydroalcoholic solutions or drying is involved; the active ingredient or diluent must have cohesive properties; good for materials prone to degredation by moisture or elevated temperature

direct compression

drug is combined with excipients and compressed to form the tablet without granulation because good quality compression enhancers are used

drugs with potassium salts, ammonium chloride, and methamine are good candidates

upper punch

presses/compacts the tablet

lower punch

removes the tablet from the press

tablets

USP evaluation requirements for _____________:

appearance, color, odor, assay, degredation, products, dissolution, moisture, friability

capsules

USP evaluation requirements for _____________:

appearance, brittleness, color, odor, assay, degredation products, dissolution, moisture, microbial limits

critical

defects in which the whole lot of the drug must be disposed

major

defects in which some of the drug must be disposed but not the entire lot

minor

defects that can be ignored

thickness

tablet ____________ can vary +/- 5%

hardness

resistance of a solid to local permeant deformation; measured by applying force to the radial axis of a tablet until it breaks

tablet should be sufficiently hard to bear mechanical stress during production, shipment, and handling

4-8 kg

oral tablet hardness

3 kg

chewable tablet hardness

10-20 kg

modified release tablet hardness

double

tablet compaction must be ____________ ended for uniformity of density distribution

picking and sticking

tablet defect that occurs during the compression process

capping and lamination

tablet defect that occurs due to excessive compression force

orange peel

tablet defect due to excessive drying during film coating

bridging

tablet defect due to insufficient flow during film coating

erosion

tablet defect due to the tablet being too soft

roughness

tablet defect due to excessive drying during film coating

friability

a tablets ability to withstand abrasion during packaging, handling, and shipment

1

only _______% weight loss or less is acceptable for a tablet during friability testing

uniformity of dosage unit

the degree of uniformity in the amount of drug substance among dosage units

can be demonstrated by unit-dose in either of two methods: weight variation or content uniformity

weight variation

assay individual tablet weight

applied when there is 25 mg or more of drug OR it comprises 25% or more by weight of the dosage form (even if less than 25 mg)

select not less than 30 dosage units, weigh 10 tablets, and use assay results to calculate the content of active ingredient assuming homogenous distribution

weight, content

when powder blended is perfected blended it is homogenous for all drugs and excipients, then _____________ uniformity is predictive of ___________ uniformity

content uniformity

assay quantity of drug in single dosage unit

select at least 30 dosage units, assay 10 individually, and calculate acceptance value (AV)

should be +/- 15% within the label claim and the RSD should be less than or equal to 6%

15

the content uniformity for the 10 assayed units should be within ________% of the label claim and the RSD should be less than or equal to 6% - if falls within these ranges, the batch is good to go

25

if one unit is outside the 15% content uniformity and no unit is outside ________% OR if the RSD is greater than 6%, 20 additional units should be tested

discarded

if more than 1 unit is outside the 15% range, any unit is outside the 25% range (of the 30 units), and the RSD is higher than 7.8%, the batch must be _________________

Disintegration

about the tablet - test measures the time required for tablets to break into particles and pass 10 mesh sieve

the breakdown of tablets into granules or aggregates to fine particles with two simultaneous processes: fluid penetration and particle separation

12

if 1 or 2 of the 6 tablets tested in a disintegration test fail to break into particles that pass through a 10 mesh sieve, repeat with _______ additional tablets and all must pass

10-30 min

acceptable disintegration time for uncoated tablets

up to 2 hours

acceptable disintegration time for coated tablets

less than (or equal to) 5 minutes

acceptable disintegration time for sublingual tablets

enteric

_____________ coated tablets should not disintegrate in gastric fluid (1 hr) and should disintegrate in intestinal fluid within a specified time

dissolution

about the drug - measures the active drug

two mainly used apparatuses: paddle affixed to a shaft or a rotating basket

moisture

measured with Karl Fischer analysis (wet chemistry technique); influences hardness, dissolution/disintegration, and chemical stability of tablet