DRUG DOSAGE FORMS & DELIVERY SYSTEMS


Suspension

Suspensions may be defined as preparations containing finely divided drug particles (the suspensoid) distributed somewhat uniformly throughout a vehicle in which the drug exhibits a minimum degree of solubility. Some suspensions are available in ready-to-use form, that is, already distributed through a liquid vehicle with or without stabilizers and other additives.

Features Desired in a Pharmaceutical Suspension
  1. A properly prepared pharmaceutical suspension should settle slowly and should be readily redispersed upon gentle shaking of the container.
  2. The particle size of the suspensoid should remain fairly constant throughout long periods of undisturbed standing.
  3. The suspension should pour readily and evenly from its container.
Physical Features of the Dispersed Phased of a Suspension

In most good pharmaceutical suspensions, the particle diameter is 1 to 50μm. Generally, particle size reduction is accomplished by dry milling prior to incorporation of the dispersed phase into the dispersion medium. One of the most rapid, convenient, and inexpensive methods of producing fine drug powders of about 10 to 50μm size is micropulverization. Micropulverizers are high-speed attrition or impact mills that are effi cient in reducing powders to the size acceptable for most oral and topical suspensions. For still finer particles, under 10μm, fluid energy grinding, sometimes referred to as jet milling or micronizing, is quite effective. By this process, the shearing action of high-velocity compressed airstreams on the particles in a confined space produces the desired ultrafine or micronized particles. The particles to be micronized are swept into violent turbulence by the sonic and supersonic velocities of the airstreams. The particles are accelerated to high velocities and collide with one another, resulting in fragmentation. This method may be employed when the particles are intended for parenteral or ophthalmic suspensions. Particles of extremely small dimensions may also be produced by spray drying. A spray dryer is a cone-shaped apparatus into which a solution of a drug is sprayed and rapidly dried by a current of warm, dry air circulating in the cone. The resulting dry powder is collected. It is not possible for a pharmacist to achieve the same degree of particle-size reduction with such comminuting equipment as the mortar and pestle.


Factors In Choosing Containers

  1. Advantage of plastic over glass containers
  2. The versatility in container dosage and consumer acceptance afforded by plastics.
  3. The interest and convenience in utilizing low and medium density polyethylene in the formation of squeeze bottles (dual function).
  4. The advent of newer techniques in drug distribution, dispensing and inventory control.
Variety of dosage forms maybe found packaged in plastic containers, such as:
  • Collapsible polyethylene bags
  • Collapsible plastic tubes
  • Plastic film
  • Plastic vials
  • Compact type container
The disadvantages of plastic packaging
  1. Permeability of the container to atmospheric gases and to moisture.
    — Leaching of the constituents.
  2. Compounds leached from the plastic containers are generally polymer additives, such as:
    • Plasticizers
    • Stabilizers
    • Antioxidants
  3. Sorption (ab or ad) of the drugs from the contents to the plastic container.
  4. Transmission of light through the container.
  5. Container deformation.

Metal Containers

Disperse systems having a consistency of a soft paste, gel, cream, or ointment can be conveniently packed into “collapsible tubes”, which are commonly made of:

  • Tin, plastic coated tin, tin coated lead
  • Aluminum, plastic coated aluminum
 
Rubber Components

Rubber of varying composition is used in pharmaceuticals and biologicals as:

  • stoppers
  • cap liners
  • parts of dropper assemblies
  • components of drip sets/infusion sets
Problems encountered in the use of rubber closures:
  • Absorption of the active ingredient, preservative or other components.
  • The extraction of one or more components of the rubber closure into the solution.
  • These problems may be corrected by:
    — using proxy clinging material (a resin that glues)
    — use of teflon in rubber stoppers (tetrafluoroethylene polymer or plastic).

Manufacturing Considerations

Manufacturing Considerations in Liquids

The rate at which the equilibrium is achieved, is highly dependent in the details of the following:

  1. Equipment
  2. Compounding Procedure
  3. Packaging Methods
  4. Labeling
  5. Storage
SUSPENSIONS

These liquids are heterogeneous systems consisting of two phases:

  1. Continuous phase
  2. Discontinuous phase
 
Methods of Preparation of Suspensions

A. By discipitation method

B. By precipitation method

  1. Organic Solvent Precipitation
  2. Precipitation effected by changing the pH
  3. By Double Decomposition Method

I. Discipitation Method

This process is done by dispersing the finely divided powders in an appropriate liquid vehicle.

The use of surfactants is desirable to ensure uniform wetting of the hydrophobic surfaces.

II. By Precipitation Methods

This is performed by effecting precipitation in the liquid vehicle.

A. Organic Solvent Precipitation

— Water insoluble drugs are precipitated by dissolving them in a water miscible organic solvent. Then adding the organic phase to purified water under standard conditions.

  • Examples of organic solvents used are ethyl alcohol, methyl alcohol, propylene glycol, acetone and polyethylene glycol.
  • A number of important considerations are involved if this method is used:
    • Particle size control
    • Correct form of crystals obtained.
    • For suspensions intended for parenterals or inhalation use, the particle size should be between 1 to 5 microns range

B. Precipitation effected by changing the pH

— This is applicable to those drugs in which its solubility is dependent on pH value.

C. By Double Decomposition Method

— Where simple chemistry is involved.

— Example is the preparation of White Lotion USP (made by interacting zinc sulfate with sulfurated potash solution to form zinc polysulfide).

Other points to be considered in preparing suspensions
  1. If a suspension is made by controlled crystallization or precipitation method, a supersaturated solution is to be formed and then quickly cooled with rapid stirring.
    — This causes the formation of many nuclei and hence, many crystals would not grow too large.
  2. In the type of the equipment to be used, it is very likely that homogenization is desired.
    — Homogenization may be accomplished by using a homogenizer or colloid mill to produce particle size of less than one micron.
3. Incompatibilities

— Some incompatibilities that may occur in suspensions are:

  • Formation of dark color upon storage
  • Separation of lipid or oleaginous components
  • Chemical reaction