Unit13Pharmaceutics

• Physical description
• Microscopic examination
• Melting point
• The Phase Rule
• Solubility*
• Dissolution*
• Particle size*

• Particle size affects solubility
• Solubility affects dissolution
• Dissolution affects absorption

formulation and efficacy

Particle size impacts the equal distribution of the active ingredient

• Solubility
• Bioavailablilty
• Taste
• Color
• Stability
• Dissolution rate
• Content uniformity
• Texture
• Stability
• Sedmentation rates

Unit of matter having a defined physical dimension

Science and technology of small particles. Study of characteristics like particle size and distribution, shape, angle of repose, porosity and others

• Particle size and size distribution
• Pore size distribution
• Particle shape
• Particle surface area
• Angle of repose
• Porosity
• Flow Properties- dusting powders
• True and bulk volumes
• Apparent density and bulkiness

When a pharmaceutical powder contains particles of wide range of sizes and shapes, then it is called polydisperse sample

When a sample has particles of same size and shape, then the powder will be called monodisperse sample

• The shape and surface area of individual particles
• The size range and number or weight of particles present

a frequency distribution curve is obtained

their average diameter is the same

Using either weight or number of the particles

• This parameter is used to describe particle size of asymmetric particles.
• Equivalent spherical diameter relates size of the particle to the diameter of a sphere having the same surface area, volume, or diameter

Diameter of a sphere having the same surface area as the particle in question.

Diameter of a sphere having the same volume as the particle in question

Equivalent sphere undergoing sedimentation at the same rate as the asymmetric particle.

This is depicted as dimension 'C' and is the diameter of a theoretical circle, which would contain the same projected area as the irregular particle.

This is the diameter of a spherical particle that exhibits the same settling velocity in the air as the irregular particle

• Sieving!!!
• Microscopy
• Sedimentation
• Coulter Counter
• Dynamic Light
• Scattering
• Laser Diffraction

• —Series of standard sieves
• Used for grading coarser particles.
• —The larger the mesh number the smaller the particle size of the powder

• —Ordinary microscope is used to measure particle size in the range of 0.2 μm to about 100 μm.
• Depth cannot be measured

—Particle size in the subsieve range may be obtained by gravity sedimentation as expressed in Stokes’ law Particle diameter corresponding to various time periods is calculated from Stokes’ law

The Coulter Principle states that amplitude of this pulse is directly proportional to the volume of the particle that produced it.

• Light from a laser is shone into a cloud of particles (e.g. cement), which are suspended in a transparent gas (e.g. air)
• The particles scatter the light
• Scattered light measured by photodetectors. This is known as the diffraction pattern for the sample.

• Affects the physicochemical properties of a drug and hence the pharmacological properties
• —Affects the route of administration
• —Formulation consideration – Flow, type, preparation
• —Stability of formulation
• —Dissolution and absorption characteristics
• —Efficacy of therapeutic agent

• Physicochemical properties like bioavailability, dissolution rate, content uniformity, taste, stability, color and texture
• —Affects flow and sedimentation rates
• —Delivery of inhalation drug substance to the correct part of the lung at the correct dose
• Packing of powders

• The smaller the size of a particle, the greater is its surface area
• The greater the surface area, the better the dissolution

Absorption of drugs

Dissolution: Only particles in the solution form pass intestinal membrane into systemic circulation for absorption

Rate of absorption for many slightly soluble drugs is limited by rate of dissolution

then the dissolution process becomes the rate limiting step

Decreased Particle Size: Increases Surface Area

Increased Surface Area: Increases Dissolution

• Reduced and uniform particle size makes the preparation smooth to touch and non-irritating

inaccurate dosing

bioavailability

• Free flow of powders to compress tablets
• Content uniformity

• Drugs with particle size between 1 – 3 µm are deposited into the alveolar region
• Larger particles deposit in the upper airways
• Particles less than 0.5 µm are either expelled or inhaled

95% of the particles should have a size 10 micrometers or less

—Finely divided particles for better texture and feel

Particle size is of great importance due to possible problems with embolism and toxicity

Mechanical process of reducing the size of fine particles or aggregates

• Manual – trituration, levigation, pulverization
• Mechanical – grinders, coffee mills

i.e. glass, when comminuting dyes and potent ingredients

• Continued rubbing of solids in a mortar with a pestle to reduce the size of the solid’s particles to a desirable degree of fineness.
• Typically w/ dry particles

• Glass, wedgewood and ceramic
• Glass mortars have smooth sides and so may not be as efficient in reducing particle size in comparison with ceramic and wedgewood

• Reduction in particle size by trituration or by spatulating on an ointment slab with addition of a non-solvent to form a paste
• To improve ease of wetting, the solvent used is generally viscous with a low surface tension

• Used for compounds that cannot be easily triturated Drug is dissolved in a minimum amount of solvent
• The solution is spread onto sides of a glass mortar or on an ointment slab as a thin layer and the solvent is allowed to evaporate.
• The fine crystals are then scraped off the surface using a metal spatula