Solid dosage (P.2)

• Solid dosage form which may or may not contain medicinal substances with or without diluents and prepared either by compression or by molding
• Scores or gloves are the line in the middle of a tablet for an easier splitting of tablets
• Caplets are capsule-shaped tablets that allow the product to be smaller than a capsule filled with an equivalent amount of powder
• Boluses are large tablets intended for veterinary use
• Coated tablets protect drug from the environment, provide barrier to the unpleasant tastes and odor of some drugs, provide special characteristics of drug release, and provide aesthetic or distinction to the product.
• Sugar coating is coated with a sugar layer that is colored or uncolored, water soluble coating which dissolves quickly after swallowing
• steps in sugar coated tablets, 1. Sealing, 2. Subcoating, 3. Smoothing, 4. Solor coating/syruping, and 5. Polishing/finishing.
• Solid Dosage Forms


  Solid in nature, intended to be administered in several routes like oral, topical, and rectal, encompass a wide range of formulations which includes tablets, capsules, powders, and granules, deliver medications in a convenient, stable, and efficacious manner
• Powders

  Dry mixtures of finely divided medicinal and non-medicinal agents intended for internal or external use, consist of finely divided particles of APIs with various excipients which may include fillers, binders, lubricants, and flavoring agents
• Micromeritics


  The science of small particles; the study of a number of characteristics, including particle size, and size distribution, shape, angle of repose, porosity true volume, bulk volume apparent density, and bulkiness
• Particle


  Any unit of matter having defined physical dimensions
• Particle Size Analysis


  • To obtain quantitative data on the size, distribution, and shapes of drug and other components to be used in pharmaceutical formulations, provides quantitative data on particle characteristics to enable the formulators and manufacturers to develop, optimize, and maintain high quality pharmaceutical products that meets the regulatory standards and deliver therapeutic efficacy
• Factors Influenced by Particle Size

  • Dissolution of particles intended to dissolve
  • Suspendability of particles intended to remain undissolved but uniformly dispersed in a liquid vehicle
  • Uniform distribution of a drug substance in a powder mixture or solid dosage form to ensure dose-to-dose content uniformity
  • Penetrability of particles intended to be inhaled for deposition deep in the respiratory tract
  • Lack of grittiness of solid particles in dermal ointments, creams, and ophthalmic creams
• Methods of Determining Particle Size

  • Sieving
  • Microscopy
  • Sedimentation Rate
  • Light Energy Diffraction / Light Scattering
  • Laser Holography
  • Cascade Impaction
• Sieve Analysis (USP / Official Method)

  Generally used for grading coarser particles, sieve # / mesh # - number of openings per linear inch used for screening materials as fine as 44 cm, disadvantage: attrition of particles, ↑ mesh number = ↓ particle size (inverse proportionality)
• Optical Microscopy


  Use of microscope to measure individual particles ranging from 0.2 um to 100 um, advantage: individual particles can be seen, disadvantage: subjective, prone to errors, very tedious (300-500 particles for good estimate), 2D image only
• Feret's Diameter


  Longest tangent line that can be measured in a particle
• Martin's Diameter


  Bisects the particle into halves
• Projected Area Diameter


  Diameter of a circle that will enclose the particle
• Sedimentation Method


  Measures the rate or free fall of velocity of particles, commonly used in determining the particle size distribution of solid particles suspended in a liquid, principle: Stokes Law - sedimentation rate is directly proportional to the density of particle, diameter of particle, and gravitational pull under same conditions, ↑ sedimentation rate = ↑ particle size (direct proportionality)
• Coulter Counter


  Principle: electric resistance, the solution that contains the suspended particle passes through a small aperture between two electrodes, while it passes, it disrupts the electric current between the two electrodes, therefore, if it disrupts the electric current, there would be a temporary increase of electrical resistance, can determine both the number and size of particles passing through
• HIAC / Royco Instrument

  Principle: light blockade, operates by passing a fluid which contains the particles through a detection zone, has a light source which illuminates the detection zone, has a photo detector that measures the intensity of light passing through, if the light passes through the detection zone, there would be blockage of the light, if the particles passes through the source of light/detection zone with light, there would be decreased detected light
• Gelman Counter


  Principle: Faraday-Tyndall Effect, ability to scatter light by colloidal particles in a fluid medium, a beam of light passes through a suspension of particles as the particles scatter light, the photo detector measures the intensity of scattered light at various angles, by analyzing the scattered light patterns, the size of the particles can be determined, the intensity of the scattering pattern gives the information regarding the size distribution of particles

  
• Comminution


  Mechanical process of reducing the size of particles or aggregates, very common in various industries including the pharmaceutical industry, its primary objective is to break down large particles into smaller particles
• Methods of Comminution

  • Trituation
  • Levigation
  • Pulverization by Intervention
• Trituation


  Process of grinding a drug in a mortar using a pestle to reduce particle size, commonly used in pharmaceutical compounding to reduce the particle size of the API ot other substances to enhance its dissolution rate, improve blending capability with other ingredients, and to facilitate tablet or capsule manufacturing processes
• Levigation


  Process of triturating a drug with a small amount of solvent liquid (levigating agent) in which the powder is insoluble, used to reduce the slight trituration, particle size of the insoluble materials, or to prepare a suspension/paste with fine particle size, also used in aiding in incorporating solid materials into a liquid vehicle to process it easier and administer like ointments, creams, and oral suspension
• Pulverization by Intervention


  Process of reducing the size of a drug with the aid of an additional material that can be removed easily after the pulverization has been completed, method of reducing the particle size of a substance with assistance of an additional material, enables particle size reduction while ensuring that the intervening material is removed from the final product which makes it suitable for pharmaceutical industrial applications
• Types of Mortar and Pestle

  • Wedgewood
  • Porcelain
  • Glass
• Wedgewood Mortar and Pestle


  For crystalline solids or hard lumps, modern prescription practice, relatively porous (absorbs liquid chemicals easily) and stains easily, interior is roughened, aids comminution, requires meticulous cleaning to remove trapped particles that may contaminate subsequent preparations, pestle may have rubber or wooden handles
• Enteric coating is used when the active ingredient is sensitive to gastric acidity, it prevents stomach irritation by protecting the drug until it reaches the intestine where it can be absorbed.
• Film coating is applied on top of enteric coatings to improve appearance and taste of the tablet. It also provides protection against moisture and light.
• Hard gelatin capsules are made up of two halves joined together at one end. The other ends are open so they may be filled with powders, granules, liquids, pastes, etc.
• The film coating layer must not interfere with the dissolution rate of the core tablet.
• Tablet coating is done using a fluidized bed system.
• Soft Gelatin Capsules are made up of soft gelatin shells containing oily substances such as vitamin A, E, D3, fish oil, cod liver oil, etc.
• The enteric coatings are made up of polymers such as cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose (HPMC), ethylcellulose, polyvinylacetate phthalate (PVAP), and sodium alginate.
• Granulation involves mixing the drug with excipients and compressing them into pellets or granules.
• Liquid-filled Hard Gelatin Capsules contain liquid medicaments such as cough syrups, eye drops, ear drops, nasal sprays, etc.
• Film-coated tablets are produced through a series of steps including granulation, compression, film coating, and packaging.