solid dosage forms

• Examples of solid dosage forms


  • Tablets
  • Capsules
  • Lozenges
  • Granules
  • Pastilles
  • Powders
• Advantages of solid dosage forms


  • Convenient
  • Clean
  • Lightweight
  • Compact
  • Dry (stable)
  • May give controlled release - doesn't spike, therapeutic window
  • Can mask taste
• Disadvantages of solid dosage forms

  • Difficult to swallow
  • Not 100% bioavailability
  • Difficult to dilute
  • Difficult for liquid drugs
• Tablet sizes


  50mg - difficult to handle

  500mg - may be difficult to swallow, soluble or chewable may be much larger
• General properties of tablets


  • Should be strong and able to withstand shock during manufacturing, packaging, shipping, dispensing and use

  Drug content must be bioavailable and able to release contents in reproducible and predictable way

  Chemically and physically stable

  Elegant product identity which is free from defects

  Uniform in weight and drug content
• Examples of tablets


  • Standard tablets

  Soluble/dispersible - exerts its effect more readily available

  Effervescent - tablets gets into solution faster

  Chewable - teeth break down to get drug into solution quickly

  Buccal

  Sublingual

  Enteric coating - to protect stomach, protect drug

  Controlled release

  Modified release
• If we set out to make 600 tablets, we may not end up with 600 tablets
• Excipients


  Everything but the active ingredient, added to aid with flow, compression, hardness, taste, tablet performance
• Moist granulation


  Mixing powdered drug with a suitable diluent

  Most widely used procedure
• It's important to test the moisture content of the granules before placing in an oven
• Purpose of granulation process


  Collecting particles together by creating bonds via compression or a binding agent
• Factors affecting granulation process


  • Particle size

  Flow characteristics

  Particle density

  Compressibility

  Moisture content
• Particle size and flow characteristics go hand in hand
• Increasing binding solution quantity increases density
• Problems that can be encountered at the granulation phase include segregation process vs separation of active ingredient
• what is the reason for adding active ingredient and disintegrant first, then binder in cube mixer


  To ensure the inside of the powder is moist, otherwise you would end up with a dry tablet inside
• Moist granulation is unsuitable when the drug is unstable with heat or moisture or produces poor granules
• Examples of diluents


  • Lactose

  Microcrystalline cellulose

  Calcium phosphate

  Calcium sulphate

  Starch

  Dextrose

  Mannitol

  Sorbitol

  Xylitol

  Sucrose
• Binder


  A pharmaceutical glue (wetting agent) which bonds particles together
• Binders are used when water may not be strong enough to create or hold a bond
• Blending


  The blades break up granules and reform them, ensures granules are moist throughout

  
• Screening


  Pass moist mass through a suitable screen (mesh) to drive evenly
• The size of the screen depends on the size of the tablets required, the larger the granules required, the larger the mesh size
• Drying


  Dry granules in tray or fluid bed dryer
• Disadvantage of tray dryer

  It doesn't dry all sides of the particle, but it is faster as granules are laid flat
• After drying, the aggregates formed need to be re-screened
• If moisture content is too low, the granules won't compress together
• Purpose of using a moisture balance before drying

  To calculate percentage moisture loss to tell you how much water there was
• Wet granulation


  Adding liquid to powder to reduce process time and equipment, water bonds powder, sometimes PVP needed
• Dry granulation


  When powders are very fine, fluffy and don't stay blended, or when it doesn't stay in the die, densify and compact the powders
• Dry granulation can be done via slugging or chilsonator
• Wet granulation often produces higher percentage of fines or non-compact products which can lead to compromised tablet quality or yield issues
• Lubricants


  Types of additives used to prevent the tablet from sticking to the die wall or punches in the tablet press
• Types of lubricants


  • Hydrophobic - stearate (magnesium, calcium salts of the free acid)

  Hydrophilic - polyethylene glycols, sodium benzoate, sodium lauryl sulphate, isoleucine, glyceryl behanate, sodium stearyl fumerate
• Purpose of glidants/lubricants


  They promote granule flow (and may prevent adhesion to punch faces) e.g. tale and fumed silica

  
• Purpose of disintegrants


  Promote disintegration of the tablet in the intestinal fluid and allow rapid drug release, possible mechanisms include swelling and elastic recovery
• Optimum disintegration is usually obtained when the disintegrant is both inside and outside the granules
• Examples of disintegrants


  • (Maize) starch, alginic acid and microcrystalline cellulose, Ac-Di-Sol
• Tablet compression


  Hopper shoe delivers granules into die

  2. Lower punch falls within the die, leaving a cavity into which particulate matter can flow under gravity

  3. Upper punch descends and the punch tip enters the cavity, confining the particles, which aggregate to form a compact (the tablet)

  4. The upper punch withdraws and simultaneously the lower punch raises until its tip becomes level with the top of the die, the tablet is thus rejected from the press
• Alternative method when moist granulation is unsuitable

  Drug, filler and lubricants are compressed into 'slugs' on a heavy duty press, then the slugs are broken down by milling and screening procedures into granules. Alternatively, the mass may be roller compacted (fed between rollers to form a compressed sheet prior to screening)