Ta ble ts Definition. Half of all pharmaceutical products are for oral use (tablets or capsules) The advantage is that they have high patient compliance, relatively easy to produce, easy to market Disadvantage the conditions in the GI tract is difficult for some substance and all substances are not absorbed
What is a tabletA compresseddispersion ofparticles.
Different types of tabletsTablets that are taken Other oralintact Conventional tablets formulations Coated Tablets CapsulesTablets that are not Oral solutionstaken intact Chewable tablets Effervescent tablets Lozenges Sublingual and buccal tablets Fast dissolving tablets
Tablet Manufacture Procurement of raw Material Preformulation Studies Formulation Mixing/Blending Granulation Compression Coating Packaging
Three Principle Methods Of Developing Powders For Tablet Making Direct Compression Wet Granulating Dry Granulating
WHY GRANULATE? To improve powder flow. To improve compressibility. To reduce fines. To control the tendency of powders to segregate. To control density. To capture and fuse small quantities of active material.
WET GRANULATING PROCESS STEPS Pre-mix Wet massing Screening Drying Milling (Sieving) Final blend (Lubricant is added)
GRANULE FORMATION IN THE WETGRANULATING PROCESS Nucleation Transition in the . funicular and capillary stage Ball growth
Rapid MixerGranulator(Wet Granulation)
DRY GRANULATING Powders can be compacted using a tablet press; this is called Slugging.
Why Dry Granulating? Granulate materials which are sensitive to heat and/or moisture. Produce a uniform particle size range. Improve flow properties. Control dust. Control bulk density. Produce uniform blends Control particle hardness.
HOW GRANULES ARE TESTED LOD- water content (Loss on drying) Bulk Density, gm/ml Particle Size Distribution Angle of Repose.
What are a tablet composed of Active substances Filler Disintegrant Binder Gliadant Lubricant Antiadherent (Coating) (Colour, humectants)
Filler / Diluent Give a reasonable size for Sugars the tablet ≥50 mg Lactose Properties Sucrose Chemical inert Mannitol Non-hygroscopic Salts Water soluble or Calcium phosphate hydrophilic Calcium carbonate Good mechanical Polymers properties Cellulose Acceptable taste Cheap
Dissintegrant Ensure that the tablet Surfactants “small” breaks into small pieces molecules that are both when in contact with water water loving (hydrophilic) Addition of Disintegrant and oil loving Intragranular addition (hydrophobic) Extragranular addition They will adsorb to Disintegration through interfaces and in water wetting increase the hydrofilicity of Surfactant that interface Disintegration through They will tend to form rupture associated structures Starch above a certain Cellulose derivates concentration
How to increase the release rate Increase the surface area (Disintegrant) Starch Cellulose materials (Avicel) Include wetting agents Surfactants Increase solubility Avoid drug-excipient interactions Use solid dispersions or solid solutions
Binder A binder is added to Dry powder that is mixed in with the granulate and increase the partly dissolved during cohesion between granulation Wet binders that are particles in dissolved in granulation granulates to liquid Gelatin and starch ensure mechanical Polividon and cellulose stability of the Dry binders that are used granulate in dry granulation Normal Cross linked PVP Microcrystalline concentration of cellulose binder is 2-10%
Lubricants and gliadants Gliadants included Lubricants to increase included to flowability of facilitate tabletting powder and ejection of Excipients formed tablets Colloidal silica Excipients Magnesium Magnesium stearate stearate Polyethylene glycol
General Formula for a Direct Compression Tablet DRUG 1 PART FILLER-BINDER 2 - 3+ PARTS DISINTEGRANT STARCH 10 - 20% OR SUPER DISINT. 2 - 5% GLIDANT COLLOIDAL SILICA 0.5 - 1% LUBRICANT MAG. STEARATE 0.5 - 1%
Advantages of Direct Compression over Granulation More economical (less Disadvantages time, space, materials, Problem of content personnel, fewer steps) uniformity for low dose Avoids heat and moisture drugs of wet granulation Not practical for large Disintegrate more dose poorly directly into primary compactible /poorly particles flowing drugs Requires tight control over physical properties of filler-binder
High Speed Production Rotary Tablet Press55 stations495,000 tabs/hour