Pharmaceutical Excipients Overview

Excipients

• Excipients are non-drug materials in a formula
• Excipients are crucial for several reasons
• Improve patient compliance (color, flavor, sweeteners)
• Increase dosage form stability (antioxidants, preservatives)
• Increase dose accuracy (diluents, fillers)
• Act as process aids (binders, lubricants)
• Improve and control drug release (disintegrants, coating agents)

Types of Excipients

• Diluents (Fillers): lactose, starch, microcrystalline cellulose
• Binders (Granulating Agents): starch, acacia, gelatin
• Disintegrants: starch, super disintegrant
• Lubricant, Antiadherent, Glidants: magnesium stearate, stearic acid

Diluents (Fillers)

• Used to bulk up tablets when the drug alone isn't enough.
• Sometimes not needed if the drug has good compressibility.
• Round tablets are typically 5-13mm; smaller or larger tablets can be difficult to handle or swallow.
• Diluents improve tablet properties like cohesion and flow.

Lactose

• Widely used diluents in tablet formulation
• Doesn't react with most drugs.
• Three forms: anhydrous, hydrous, spray-dried
• Anhydrous is better for aging as it does not discolor (Maillard reaction).
• Anhydrous can absorb moisture and turn into hydrous form in humid environments.
• Hydrous form is often used with wet granulation.

Starch

• Derived from corn, wheat, or potatoes
• Used as diluent (50-60%), binder (2-10%), or disintegrant (5-20%) depending on the formula's needs.
• Added as a powder or paste in specific stages of tablet production.

Other Diluents

• Dextrose: Available as hydrous and anhydrous forms.
• Can be used as a replacement for lactose to minimize discoloration with alkaline compounds
• Mannitol: Used widely in chewable/orodispersible tablets due to its sweet taste, slow solubility and lack of hygroscopicity.
• Expensive, poor flow, requires high lubricant level

Microcrystalline Cellulose

• Often referred to as Avicel®
• Multipurpose excipient used as a diluent and disintegrant
• Inert, can be used with alkaline or acidic substances (no discoloration).
• High purity and low moisture content
• Directly compressible due to good compressibility and flowability
• Avicel-containing tablets have short disintegration times, high hardness, low friability and low variation in weight.

Binders (Granulating Agents)

• Bind particles together to form granules/compacts.
• Include acacia, tragacanth, gelatin, starch -paste.
• Acacia and tragacanth are natural gums and are more effective as solutions.
• Gelatin is a synthetic protein, preferred over acacia and tragacanth.
• Starch paste is a commonly used granulating agent.

Modified Natural Polymers

• Common binders such as Alginates, methylcellulose (MC), ethyl cellulose (EC), hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC)
• (Except for EC), used in powder form or as solutions.
• HPC can be used in alcoholic solution.
• EC is insoluble in water, used in alcoholic solution to prevent tablet disintegration.

Disintegrants

• Oppose the effect of the tablet binder, and physical force (applied during compression).
• Facilitate breakdown of tablets in GI fluids.
• Example of disintegrating agents are starch, and super disintegrant.

Starch (Disintegrants)

• Most widely used due to low cost.
• Quick water uptake and swelling leads to tablet rupture.
• Super disintegrants (Explotab®, croscarmellose sodium, crospovidone): powerful disintegrating agents
• Used at ratios of 5-20% of the tablet weight.

Lubricants, Antiadherents and Glidants

• Lubricants reduce friction during tablet ejection from the die cavity.
• Antiadherents reduce sticking of granules to die walls.
• Glidants promote granule flow by reducing friction between particles.
• Lubricants help with production and may influence bioavailability.
• Lubricants should be added to the surface of granules.
• Small particle size 200 mesh, larger particle size decrease efficacy.
• Mixing time (2-5 mins) and mixing rate (high mixing rate causes penetration and decreases efficacy) influence efficacy.
• Magnesium or Calcium stearate is the most widely used lubricant.
• Stearic acid is less effective than the salts, not used with alkaline drugs.
• Zinc stearate is effective in direct compression and is inert.
• Talc may also be used as a lubricant (contains iron so it has to be applied carefully).

Tablet Design and Formulation

• Tablet formulation involves weighing, granulation(wet/dry granulation is used for wet granule process / dry granule process / direct compression) , mixing, and compression.
• A crucial stage of the manufacturing process, uniform distribution (mixing), and adequate (appropriate/proper) distribution of lubricants is essential.

Mixing

• A critical step in tablet formulation.
• Uniform distribution of tablet constituents.
• Allows proper distribution of lubricants.
• Undermixing leads to impaired content uniformity, poor flow properties
• Overmixing leads to problems in the tablet manufacturing process such as poor flow properties due to lubricants entering into the tablet granules.

Granulation

• Addresses flowability and compressibility issues common in fine powder drugs.
• Granules have better flowability and compressibility than individual ingredients.
• Ensures the consistent distribution of API (active pharmaceutical ingredient) in the formulation.

Wet Granulation

• Common method using liquid binder.
• More steps; better control over the process.
• Involves mixing active ingredients, excipients and a liquid binder , followed by drying and milling to achieve the desired size.

Dry Granulation

• Used when granulating solutions are not suitable, especially with heat-sensitive drugs.
• Involves mixing drug powder, inactive ingredients and passing them through a roller, creating slugs, then milling/screening to the required size.

Direct Compression

• A method used when the drug and excipients are suitable for direct compression.
• Avoids a granulation step.
• Advantages include simplicity, lower labor and risk of ingredient deterioration.
• Requires certain properties in the active ingredient and/or excipients (crystalline nature and easy compressibility), limitation arises if intermolecular interaction is weak.

Compression

• Final step; requires careful evaluation of factors beyond this overview.

Tablet Compression Machine

• Comprises of a hopper, dies, punches, cam tracks.
• Also includes auxiliary equipment, such as automatic feeders and dusters (beyond this scope)

This quiz provides an overview of pharmaceutical excipients, detailing their types and roles in drug formulations. Learn about diluents, binders, disintegrants, and other crucial components that improve patient compliance and drug stability. Test your knowledge on how excipients contribute to effective drug delivery.