DDS Lecture 18 Content

Tablets

• solid dosage forms containing medicinal substances with or without suitable diluents

Tablet shapes

• roung

• oblong

• oval

• triangular

• square

• rectangular

• hexagonal

• heart

Tablet Advantages

• accurate dosage/minimum variability

• absence of alcohol

• concentration variability

• elegance

• patient acceptance

• convenience (light and compact)

• tamper resistant

• low cost

• easiest/cheapest to package and ship

• production identification is simple

• ease of administration

• special release profiles possible

• suited for large-scale production

• best overall properties of all oral dosage forms

Tablet Disadvantages

• swallowing

• difficult to extemportaneously prepare

• some drugs resist compression

• poorly wetting drugs, slow-dissolving drugs, intermediate to large dosages

  • different bioavailabilitites

  • very difficult to use for tablet

• bitter taste/bad odor

• oxygen/moisture-sensitive require coating

Qualities of Good tablet

• accurate and uniform weight

• homogeneity

• absence of incompatibilities

• stability and hardness

  • too hard: won’t dissolve

  • too soft: break down during handling

• ease of disintegration

• reasonable size and shape

• pleasing appearance

• ease of manufacturing

• economy of production

Tablet hardness

5-6 kg

Tablet thickness

2.0 mm

Tablet weight

200 mg ± 5%

Tablet content uniformity

95%-102%

API contained is within this range (measured by HPLC drug assay)

Tablet disintegration

<5 minutes

Non-oral tablet routes

• implanted

• vaginal

General types of tablets

• molded

• compressed

Types of tablets (expanded)

• compressed

• multiple compressed

• sugar-coated

• film-coated

• gelatin-coated

  • helps make swallowing easier

• enteric-coated tablets

  • dissolve in intestine

  • coated by Eudragit polymer that dissolves in basic pH, not acidic pH (stomach acid)

• buccal and sublingual

  • low hardness

• chewable

• effervescent

  • citric acid, sodium bicarbonate

  • when placed in water, makes CO2

• molded

• tablet triturates

• hypodermic

• dispensing

  • big tablet to make other dosage forms out of

• immediate-release

  • fast dissolving, rapidly disintegrating

• instantly-disintegrating or dissolving

  • lyophilized foam

  • compression

• extended-release

• vaginal

Tablet Quality standards and compendial requirements

• tablet weight

• USP Weight variation test

• Content uniformity

• tablet thickness

• tablet hardness and friability

• tablet disintegration

• tablet dissolution

Compressed Tablet Manufacturing: Wet Granulation

• weighing and blending

• preparing the damp mass

• screening the damp mass into pellets or granules

• drying granulation

• sizing granulation by dry screening

• adding lubrication and blending

Other compressed tablet manufacturing

• all-in-one granulation methods

• dry granulations

  • slugging

  • roller compaction

• tableting of granulation

• direct-compression tableting

  • tablet dedusting

Medication

active drug

Excipients

• all other ingredients

• inert substances used to give preparation a suitable form or consistency

Diluent

• added to increase bulk

• lactose, sucrose, starch, mannitol

Binders

• adhesive

• used to hold powders together

• water, alcohol, 15% starch paste, 70% sucrose syrup, 15% gelatin mixture

Disintegrants

• aid in breaking up tablet

• starch, cellulose derivatives

Lubricants

• improve powder flow properties (in manufacturing)

• decrease adhesion to punch/die

• decrease friction to punch/die and facilitate tablet ejection

• reduce punch/die wear

• Ca/Mg stearate, starch, NaCl, talc, waxy materials

Glidants

• improve flow properties of powders

• colloidal silicone dioxide, talc

Other tablet excipients

• coloring agents

• flavoring agents

Multiple Compressed Tablets

• prepared by subjecting the fill material to more than a single compression

• generally, sequential and alternate fill-compress-fill-compress etc.

• 2 different drugs in 2 different layers

  • core of one drug and shell of other

  • layered tablet of two drugs
    

Sugar-coated tablets

• compressed

• may or may not be colored

• long process of layering on multiple coats

Film-coated tablets

• compressed

• thin polymer coating layered onto tablet as thin film

  • sprayed on

Gelatin-coated tablets

• compressed

• coated with thin layer of gelatin

• facilitates swallowing

Enteric-coated tablets

• delayed release

• coating generally dissolves in a higher pH range (eg. after moving into small intestine)

• protects drug at acidic pH range

• coating: eudragit

Buccal and Sublingual tablets

• designed to be dissolved in the buccal pouch or under the tongue

• drug absorption may occur through oral mucosa

• protects from gastric juices

Chewable tablets

• for children, adults with difficultly swallowing

• flavoring is important

• must be chewed, should not be swallowed whole

  • counseling

  • intended to be absorbed buccally

Effervescent tablets

• compressed

• contain effervescent salts that release carbonation when placed in water

• Alka-Seltzer

• Zantac EFFERdose

Molded tablets

• tablet triturates may be prepared by molding

• use mold, not compressed

Tablet Triturates

• small, usually cylindrical, molded or compressed tablets

• may be used in compounding

Hypodermic tablets

• no longer available

• originally used by physicians for making injections

• tablets dissolved in suitable vehicle

• questions about sterility of injection

Dispensing tablets

• compounding tablets

• high-strength tablets used as source of drug for compounding

• not for dispensing to patients

Immediate-release tablets

• standard compressed tablets

• not instant release

Lyophilized foam tablets

• instantly disintegrating

• mixture poured into mold and lyophilized

• mold containing tablet may be integrated package

Compression instantly disintegrating tablet

mildly compressed tablets containing super-disintegrants

Extended-release tablets

• aka sustained release, controlled release

• barrier layers (made of polymers) control the surface area diffusion of drug out of core

  • slow diffusion

• core of hydroxypropyl methylcellulose (HPMC) matric that contains active drugs

Vaginal tablets

• inserts

• generally compressed

Compressed tablets punches

• countours of the punches determine the shape of the tablets

• shapes: flat face, shallow cup, standard cup, deep cup, modified ball

Tablet quality control

• size/shape, unique markings, organoleptic properties, hardness

• weight variation

• tablet thickness

• tablet hardness

• friability

• content uniformity

• tablet disintegration

• tablet dissolution

USP Required Weight Variation Test

• take 20 tablets from lot

• mass each, and calculate average mass

• no more than two tabs may vary from mean %

• for 130 mg tab: > 10%

• for 324 mg > 5%

  • tablets over 130 mg

Tablet Thickness Quality Control

• thickness of individual tablets is measured with micrometer

  • gives info about variation btwn tablets

• should be within ±5% variation of standard value

• any variation in thickness within particular lot of tablets or between manufacturer’s lots should not be clear tot the unaided eye for consumer acceptance of the product

• thickness controlled to smooth progress of packaging

Hardness test

• hardness: force necessary to break tablet diametrically

• aka tablet crushing strength

• test: tablet located between 2 anvils and force applied

• strength required to break tablet noted

• oral tablets: 4-10kg hardness

• hypodermic/chewable: 3 kg hardness

• sustained release: 10-20 kg hardness

Friability test

• tablet’s durability

• maximum weight loss of not more than 1% is generally acceptable

• B = 100(W0-W)/W0

• B: % loss of weight

• W0: weight before test

• W: weight after test

Content Uniformity control

• for tablet with drug (ex. 50 mg), need content uniformity test

  • ex. low dose, high potency tabs

• measure % of drug present of the label value in each tablet

• monograph sets guides between 85-115% on label

• drug assay: HPLC

Tablet disintegration

• uncoated tabs: 30 min

• coated tabs: 2 hours

• sublingual: 3 min

• use disintegration tester

Tablet dissolution

• dissolution: method by which solid solute enters solution

• 2 objectives of in-vitro dissolution tests:

  • show drug release from tablet is as close as possible to 100%

  • show rate of drug release is uniform batch to batch and is the same as the release rate from those batches proven to be bioavailable and clinically effective

• 2 apparatuses: paddle, basket

  • paddle: tablets, 50 rpm

  • basket: capsule, 100 rpm

  • both use 900 mL of dissolution medium

Tablet coating types

• film (polymer)

• sugar

Sugar coating features

• rounded, high polish

• 30-50% weight increase

• break lines not possible

• multistage process

• 8 hour process

Film coating

• retains contour of original core, not as shiny

• 2-3% weight increase

• possible break lines

• single step process

• 1.5-2 hour process

• preferred

Tablet coating purposes

• protection of active ingredient from air/humidity

• to mask taste of bitter API

• modify the drug release (enteric coating)

• to enhance patients appeal

Tablet coating process

• coating solution moves through tubing to coater by using peristaltic pump

• solution atomized by spray nozzles creating droplets

• initially wet droplets adhere to the tablet surface

• coating solution disperses evenly and accumulates on the surface and partially dries

• additional coating solution covers tablet while drying

• coalescence and final drying of the spraying solution yields a finished tablet

Dry granulation

• slugging

• roller compaction

Tablet presses

• single punch

• multiple punch

• rotary punch

  • widely used

Basic components of a tablet press

• hopper for holding/feeding granulation

• dies that define the size/shape of tablet

• punches for compressing the granulation within the dies

• cam tracks for guiding the movement of the punches

• feeding mechanism for moving granulation from the hopper into the dies

Processing problems

• capping

• lamination

• sticking

• picking

• mottling

Capping

partial for complete separation of the top or bottom crowns of a tablet from the main body of the tablet

change binding agent

Lamination

separation of tablet into two or more distinct layers

change binding agent

Sticking

tablet material adhering to the die wall

solved by adding lubricant

Picking

surface material from a tablet is sticking to and being removed from the tablet’s surface by a punch

solved by adding lubricant

Mottling

unequal distribution of color on a tablet, with light and dark areas standing out in an otherwise uniform surface

solved by coating, adding coloring agents

Lozenges

• prepared by compression or molding

• designed to be slowly dissolved in the oral cavity

• aka troches

Lollipop

• sugar-based lozenge

• lozenge on a stick

• ex. Actiq (Fentanyl)

Molded tablets

small tablets made by molding a soft mass that usually consists of a potent medication diluted with lactose and moistened with alcohol

Preparation of molded tablets

• drug added to diluent (lactose/dextrose/sucrose)

• moisten with alcohol or 50% alcohol

• mix into pasty mass

• fill holes in top portion of mold

• press top portion of mold over lower and press to place the tablets on the pegs

• dry, remove, and package

Packaging and storing tablets

• room temperature

• depends upon active drug characteristics

Stability

• according to USP 797

• 5 months if prepared from USP/NF ingredients

• 25% of expiration period remaining if prepared from commercial products

• can be changed based upon available documentation

Pellets/Implants

small, sterile rods or ovoid-shaped tablets, often implanted

Pastilles

soft variety of lozenge, consisting of a medicament in a gelatin base

Pills

• small, round, or egg-shaped solid bodies for internal use

• 60-300 mg in weight

• Parvules, granules

• greatest popularity: about 100 years ago

• “pill roller”: all formerly made by hand

Preparation of pills

• active

• liquid (water, ethanol, glycerin)

• vehicle (tragacanth, acacia)

• mix in mortar, poll into pipe, divide, shape into spheres, dry