Tablets

Tablet Defects

-Capping & lamination -Picking & sticking -Mottling & Double Impression -Weight variation -Hardness variation

Excipients of Tablets

-Diluents/bulking agents/fillers -Binders -Disintegrants -Lubricants

Film Coating Problems

-Sticking & peeling - sticks to pan or another tablet -Orange peel effect - texture of coated surface like surface of an orange -Bridging & filling - filling & obscuring monograms/scoring on tablet core

Types of Tablet Coating

-Sugar -Film - Aqueous/non-aqueous -Compression -Enteric

Accu-B

Accu-Break Technologies Type: (bilayer) - Top layer contains single/combination of drugs, bottom layer drug-free

Accu-T

Accu-Break Technologies Type: (trilayer) - single drug in two layers, drug layers separated by scored/unscored drug-free layer -Accu-T® AIB - trilayer - 2 different drugs in 2 layers, drug layers separated by scored/unscored drug-free layer -Accu-T® CR - multilayer - 2 different drugs in immediate release & controlled release layers, layers: drug, inactive, drug

Binders

Excipients which add cohesiveness to powders, thereby provide necessary bonding to form granules •Natural e.g. Starch: as 10-15% paste, most common •Synthetic - have different solubilities (water, alcohol, etc.)

Diluents

Excipients which make up major portion of the tablet when drug & other excipients are inadequate to produce the bulk -Lactose -Mannitol -Cellulose derivatives: Microcrystalline cellulose & Directly compressible diluents -Inorganic salts -Calcium phosphate anhydrous

Lubricants

Excipients which: •reduce friction during tablet ejection between walls of tablets & walls of the die cavity e.g. Stearic acid, salts - Magnesium Stearate (most common) •antiadherents •glidants

Disintegrants

Excipients which: •facilitate breakup of tablets in contact w/ water in GIT •draw water into tablet through pores, swell & finally cause tablet to burst apart

Dry granulation

Method of preparation of tablets: •drugs Sensitive to Moisture and Heat (e.g. Aspirin, Vitamins) •too high dose for direct compression •powder mixture either compressed into large flat tablets (slugging) or pressed in between rollers to increase particle density (roller compaction), followed by breaking of the slug/compact mass & passing through sieve to obtain granules

Wet granulation

Method of preparation of tablets: •most widely used, excellent physical properties •liquid (mostly water) mixed w/ powders, passed through sieves, dried to obtain granules, then compressed

Direct Compression

Method of preparation of tablets: •simple, fast •Heat and Moisture Sensitive drugs •Powders must have Good Flow Properties •Powder mixture is Directly Compressed (no granulation)

Lamination

Tablet defect: Separation of tablet into 2 or more distinct layers •Reasons: entrapment of air during compaction, excess of fine, insufficient binder, not enough moisture, worn tooling •aged tablets under improper storing

Capping

Tablet defect: partial/complete separation of top/bottom of tablet from main body •Reasons: entrapment of air during compaction, excess of fine, insufficient binder, not enough moisture, worn tooling •aged tablets under improper storing

Sticking

Tablet defect: refers to tablet material adhering to die wall

Picking

Tablet defect: small amt of material from tablet is being removed off tablet surface & sticking to punch face -of concern when punch tips have engraving/ embossing letters

Mottling

Tablet defect: unequal distribution of color on tablet surface -Reasons: drug has different color from excipients, degraded drug becomes colored, improper mixing of color w/ powder

Double impression

Tablet defect: when upper or lower punch have monogram/other engraving

Aqueous film

Type of tablet (film) coating: water as solvent film forming polymer -HPMC, HPC (water soluble celluloses) plasticizer (glycerin, PEG) vehicle/solvent (water to make 100%)

Non aqueous film

Type of tablet (film) coating: water is not solvent/polymer not soluble in water polymer (insoluble in water) - Cellulose Acetate phthalate plasticizer - Castor Oil sometimes pigment (aqueous/nonaqueous) solvent Surfactant - enhance spreadability of film during application, ex. Span/Tween

Sugar

Type of tablet coating: application of powder w/ sugar binder syrup •oldest method •aqueous solutions of sucrose are deposited repeatedly on the tablets until smooth, aesthetic pleasing coat is formed •tedious, time consuming, pan specific & requires expertise of skilled technicians, results in coated tablets that may be twice the size and wt of original uncoated tablets

Film

Type of tablet coating: polymeric material as main component • deposits thin polymer film onto tablet surface • Advantages: speed, reduced production space, minimal weight increase (2-4%) -Types: Aqueous and Non aqueous

Enteric Coated Tablets

Type of tablet: Have delayed release features do not disintegrate in the stomach Designed to release drug in intestine (pH 5-7) Purpose: •for drugs that degrade in stomach •for drugs that irritate gastric mucosa •bypassing the stomach may substantially enhance drug absorption

Film coated tablets

Type of tablet: Thin polymer coating on already compressed tablets water soluble/insoluble polymer layer designed to rupture/dissolve in GIT

Sugar coated tablets

Type of tablet: colored/uncolored sugar coating on already compressed tablets water soluble coating dissolves fast

Effervescent Tablets

Type of tablets: compressed effervescent mixture tablets placed in water & then taken Purpose: rapid disintegration & increase palatability

Lozenges/troches

Type of tablets: dissolve slowly in the mouth for local effects in mouth & throat most excipients water soluble, e.g. sorbitol, gelatin

Lactose

_ (crystalline), anhydrous _, spray-dried _ (3% moisture) -most common Diluent/filler in tablet -dry/wet granulation, rapid dissolution in water, pleasant taste, good compatibility w/ many drugs -low cost -Limitations: _ intolerance, anhydrous _ absorbs moisture

Non-official

_ methods to evaluate tablets: Thickness Hardness Friability

Official

_ methods to evaluate tablets: Weight variation Content uniformity Disintegration Dissolution

Sublingual Tablets

_ tablets dissolve PROMPTLY beneath the tongue absorbed through oral mucosa from both tablets Purpose: •drugs destroyed by gastric juice •drugs poorly absorbed from GIT •avoid first-pass effect

Buccal Tablets

_ tablets dissolve SLOWLY in buccal pouch absorbed through oral mucosa from both tablets Purpose: •drugs destroyed by gastric juice •drugs poorly absorbed from GIT •avoid first-pass effect

Accu-Break Technologies

accurate tablet splitting through drug free layer in bilayer tablets easy to break, no waste from crumbling tablets Two types: Accu-B & Accu-T

Instantly disintegrating/dissolving tablets

aka Rapidly Dissolving tablets highly water-soluble excipients disintegrate/dissolve in mouth w/in 1 min or even w/in 10 sec before swallowing prepared in molds (not compressed) ex. Zydis®

Caplets

capsule shaped uncoated/film-coated tablets easy to swallow

Cellulose Acetate Phthalate

example of material used in Enteric Coating

Gelatin coated tablets

geltabs-tablets coated with gelatin easy to swallow, tamper evident

Magnesium Stearate

most common example of lubricant excipient in tablets

Advantages of Tablets

safe & convenient stability over liquid dosage forms variable dosage strengths better patient compliance less expensive than capsules immediate, delayed, controlled release ranges taste (by coating) easy identification

Tablets

solid dosage forms prepared by compression/by molding & contain medicinal substances most given orally, others given sublingually/buccally some are scored, which allows them to easily be broken

Chewable tablets

tablets are chewed & then swallowed rapid and complete disintegrate (taken w/o water) large tablets that are difficult to swallow *disintegrants not used* *flavors, colors & others, e.g. mannitol/sorbitol*

Enteric

type of coating: •intended to pass through the stomach intact to disintegrate & release drug content for absorption along intestines •materials used Cellulose Acetate Phthalate, HPMC Phtthalate, pharmaceutical shellac

Compression

type of coating: dry coatings w/ doubled compression steps to get a "compression-coated" tablet •compaction of granular coating materials around a tablet •tablet w/in a tablet •needs specialized tablet machine, e.g. Manesty Drycota ®, Manesty Bicota® •Purpose --to separate incompatible drugs (in core & coating layer) --coat tablets containing solvent (water & organic solvent) sensitive drugs •Disadvantage - complex compressing machine required

Disadvantages of Sugar coated tablets

•Up to 50% increase in tablet size, wt & shipping cost •Time consuming manufacturing process --require specialized expertise --not appropriate for diabetics

Purpose of Granulation

•increase bulk density of powder mixture making sure whole amt can be filled into die •improve flowability of powders leading to reduction of tablet weight variation •improve mixing homogeneity, avoid smaller particles separating out •improve compactability •ensure homogeneity of colors

Advantages of Sugar coated tablets

•protect from environmental factors •masks objectionable taste/odor •enhance appearance •possible imprinting

Advantages of Film coated tablets

•same as Sugar coated tablets plus: •more durable & less bulky than sugar coated tablets •less time consuming/expensive than sugar coating •may/may not alter dissolution profile of the drug (functional film/non-functional film)

Disadvantages of Tablets

Powders/granules may not be compressible Not prepared extemporaneously Difficulty in swallowing Bioavailability problem w/ poorly water-soluble drugs local irritation/other harmful effects to GI mucosa Difficulty adjusting dose if not scored