Excipients and Tabs

Manufacturing advantages of Tablets

simplicity, economy of preparation, stability, convenience in packaging, shipping, and dispensing

Consumer advantages of tablets

Accuracy of dosage, compactness, portability, blandness of taste, ease of administration

Types of excipients

diluents, binders, Disintegrates, Lubricants, Glidants, coatings

What is a diluent? What are common the ingredients?

Substance used to increase the bulk weight of a tablet, majority of the weight in tab/cap. Clays, salts, insert sugars (dextrose, sucrose, glucose, lactose), polysaccharides

What is a binder? What are common binders?

glues; ensures the tablet remains intact, improves flowability. Sugars, polysaccharides/gums (starch, cellulose derivatives, avicel gum arabic, sodium alginate), gelatin

What is microcrystalline cellulose?

Linear polymer of beta-1,4 linked D-glucose derived from bleached wood pulp. Inert, very stable, insoluble, very good flow characteristics, plays multiple roles in tabs

What are cellulose derivatives?

Carboxymethyl cellulose→ soluble in cold and hot water

Hydroxypropyl methyl cellulose→ soluble in cold water

Properties depend on how many OH groups are substituted, high viscosity, non-toxic, hypoallergenic, non-digestible, plays multiple roles in tabs

What are the properties/characteristics of starch?

Branched polysaccharide consisting of alpha-1,4-linked and 1,6-linked D glucose units. Non-toxic, easily digestible, better solubility than cellulose derivatives, cheap, relatively inert, plays multiple roles in tabs

What is PVP?

water and alcohol soluble, very useful as a binder for drugs that are not soluble in water

What are the consequences of too much/strong of a binder?

Will make a hard tablet that will not disintegrate, if the API is adversely affected by an aqueous binder, a nonaqueous binder can be used (PVP in alcohol), or a binder can be added in dry form

What is a disintegrate?

Added to tab to facilitate its breakup or disintegration after administration. Most important quality is to absorb water rapidly. One part of disintegrate is added to the powdered formula prior to granulation, and the remainder is mixed with the lubricant and added prior to compression

What are good disintegrates?

Best disintegrants are polymers with good water absorbing/swelling properties. Starch, clays (bentonite), polysaccharides (agar, CMC, methylcellulose, avicel, alginic acid)

What are super disintegrants? what are common types?

swell 7-12 times <30 seconds, accelerate disintegration 100x, very useful for difficult-to-dissolve drugs. Crosslinked carboxymethyl cellulose (Croscarmellose, Primellose), crosslinked polyvinyl pyrrolidone (Crospovidone), sodium starch glycolate (Primojel)

What is the mechanism of swelling of disintegrates?

1. Multiple water bonding

2. Formulation of 3D network

3. Entrapment of large amounts of water

4. Development of elastic force acting to break the tablet

What are lubricants? What are common types?

Prevent adhesion of the tablet to the surface, improve the flowability of granules, often-water repelling materials. Fatty acids (stearic acid, magnesium stearate, hydrogenated veg oil), PEG

What happens if excessive amounts of lubricant is added?

Results in “waterproofing” the tab, resulting in poor disintegration and dissolution

What are glidants? What are common types?

Improve the flow of granules/powder materials by correcting surface irregularity interparticular friction and decreasing surface charge. Glidant particles absorb on granule surface, prevent adhesive interactions between granules (increase flowability by decreasing AOR). Talc, magnesium stearate, PEG

Why are coatings useful?

Improve drug stability, mask taste/odor, easy to swallow, product ID, improve handling, modify drug release

Why is granulation important?

Ensures homogenous mixing of the ingredients, improves flow, improves compressibility of the tablet

What is wet granulation?

Solutions of the binding agent are added to the mixed powders with stirring, or water is sprayed on the mix

What are the disadvantages of wet granulation?

Time, labor, necessity to dry the mixture (some API are heat sensitive)- tray or fluid bed drying, residual moisture

What is dry granulation?

simpler and cheaper than wet, used when API is sensitive to moisture or unable to withstand elevated temps, used when the tab ingredients have sufficient inherent binding or cohesive properties (microcrystalline cellulose), eliminates a number a steps

What is direct compression?

Least preferred method; reserved for a small group of drugs having all the physical characteristics required for the formulation of a good tablet, used when the drug dose is large

For direct compression, what binder can be used?

Avicel (MCC)