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• Liquids

  Advantages: Ease of administration, Immediate availability for absorption - more rapidly and efficiently absorbed compared to tablets or capsules

  Disadvantages: Technical problems (instability), Special techniques required for poorly soluble drugs, Requires pharmaceutical elegance with regards to taste, appearance and viscosity
• Causes of instability in liquids

  • pH
  • Temperature
  • Concentration of the Reactants
  • Light or Radiation
  • Packaging Component
• Factors that affect Light/Radiation

  • Intensity of the wavelength of light
  • Size of the container
  • Shape of the container
• Glass container types

  • Type I - Highly Resistant Borosilicate Glass

  Type II - Treated Soda Lime Glass

  Type III - Soda lime Glass for Dry Products

  Type IV - General Purpose Soda lime Glass
• Powdered Glass Test


  Performed on ground or powdered glass to expose internal surface, Tests the leaching potential of the glass, Alkali treated with 0.02 N sulfuric acid (acidimetry)
• Water Attack Test


  Exposure of the glass with sulfur dioxide at 121°C, Specifically performed with TYPE II GLASS
• Plastic containers

  • Polyethylene

  Polystyrene

  Polypropylene

  Polyvinyl chloride

  Polyethylene terephthalate
• Plastic containers


  • Cannot be autoclaved, Low density = droppers and sprays, High density = solid oral preparations, Autoclavable, Rigid and has good clarity, Used for blister packaging, Carcinogenic, For beverages, Have transparency and luster, Gamma radiation sterilization
• Metal containers


  • Tin

  Plastic coated tin

  Tin coated lead

  Aluminum

  Plastic coated aluminum
• Metal containers


  Disperse systems having a consistency of a soft paste, gel, cream, or ointment can be conveniently packed, Designed to release pressurized contents, May contain toxic metals, "Container may explode if heated"
• Rubber containers


  • Stoppers

  Cap liners

  Parts of dropper assemblies

  Components of drip sets/ infusion set
• Problems with rubber closures

  Absorption of the active ingredient, preservative or other component or leaching, Extraction of one or more components of the rubber closure into the solution
• Correcting problems with rubber closures

  Using epoxy clinging material (a resin that glues), Use of teflon in rubber stoppers (tetrafluoroethylene polymer or plastic)
• Factors in choosing containers

  • Advantage of plastic over glass containers: Lightness of weight, Resistance to impact, Lower transportation costs, Lower losses due to less container damages

  Versatility in container dosage and consumer acceptance afforded by plastics

  Interest and convenience in utilizing low and medium density polyethylene in the formation of squeeze bottles (dual function)

  Advent of newer techniques in drug distribution, dispensing and inventory control
• Variety of dosage forms in plastic containers

  • Collapsible polyethylene bags

  Collapsible plastic tubes

  Plastic film

  Plastic vials

  Compact type container
• Disadvantages of plastic packaging

  • Permeability of the container to atmospheric gases and to moisture

  Leaching of the constituents: Plasticizers, Stabilizers, Antioxidants

  Sorption (ab or ad) of the drugs from the contents to the plastic container

  Transmission of light through the container

  Container deformation
• Techniques for poorly soluble drugs

  • Co-solvency

  pH control

  Solubilization

  Complexation

  Hydrotrophy

  Chemical Modification of the drug
• Solubility


  Co-solvents may be used in the formulation of aqueous liquid, such as alcohol, sorbitol, glycerin, propylene glycol
• Stability


  Physical stability is shown by the maintenance of the physical properties such as the color, clarity, taste, viscosity, and odor throughout its shelf life or until the expiry date is reached. Chemical stability is also considered in the formulation because the instability is magnified in solution as against solid and suspension systems.
• Organoleptic characteristics

  • Taste (flavoring): Selection, Evaluation

  Appearance: Color and clarity
• Classification of preservatives

  • Acidic: Alkyl esters of p-hydroxybenzoic acid (PABA), benzoic acid and its salts, Boric acid and phenols (for external use)

  Neutral: Benzyl alcohol, phenylethyl alcohol

  Mercurials: Thimerosal, nitromersols, phenyl mercuric acetate/ nitrate

  Quaternary Ammonium Compounds: Benzalkonium chloride, cetyl pyridinium chloride
• Parabens


  The most useful preservatives because they are chemically stable, neutral in pH, non-toxic, non-irritating, nonallergenic, and possess both antifungal and antibacterial properties
• Sweetening agents


  • Sucrose: Can be obtained in highly purified form, chemically and physically stable at pH 4 to 8, Can be used in conjunction with polyols to prevent crystallization. Disadvantage: "cap locking"

  Liquid Glucose: Extremely sweet viscous substance, imparts both body (viscosity) and sweetness

  Artificial Sweeteners: Saccharin and cyclamates
• Artificial sweeteners


  Sodium and Calcium salts of saccharin are soluble in water, alcohol and polyols, Stable at pH 3 to 8, Produce the desired sweetness at a much lower concentration than sucrose. Cyclamates are 15 to 30 x sweeter than sucrose, Saccharin is 250 to 500 x sweeter than sucrose.
• Viscosity


  If high concentrations of carboxymethylcellulose (CMC) are used, incorporation of Al+3, Fe+3, and Ca+2 are done. Viscosity controlling agents are PVP, methylcellulose and sodium CMC.
• Manufacturing considerations in liquids

  • Equipment

  Compounding procedure

  Packaging methods

  Labeling

  Storage
• Colloids


  Defined as the intermediate between solutions and precipitates, Larger than the molecules and ions that make up the solutions, A two-phase heterogeneous mixture made up of a dispersed phase of tiny particles that are distributed evenly within a continuous phase
• Colloid example


  • Homogenized milk is a colloid made up of tiny particles of liquid butterfat (the dispersed phase) suspended in water (the continuous phase)
• Dispersed systems


  • Dispersed particles (dispersed phase)

  Dispersing medium (dispersing phase)
• Size classification

  • Molecular dispersion

  Colloidal dispersion

  Coarse dispersion
• Dialysis

  Used to separate colloidal particles from molecules and ions, Small molecules and ions can pass through the semi permeable membrane while colloidal particles are retained
• Ultrafiltration


  Used to separate and purify colloidal material, Conducted under negative pressure (suction) through a dialysis membrane supported in a Buchner Funnel
• Electrodialysis

  A purification process by which charged impurities such as ionic contaminants are removed from dialysis or ultrafiltration using an electronic potential across the membrane
• Pharmaceutical applications of colloids

  • Colloidal silver chloride, silver iodide and silver protein are effective germicides and do not cause the irritation that is characteristic of ionic silver salts

  Coarsely powdered sulfur is poorly absorbed when administered orally, yet the same dose of colloidal sulfur may be absorbed may be absorbed so completely as to cause toxic reaction and even death

  Colloidal copper has been used in the treatment of cancer, colloidal gold as a diagnostic agent for paresis and colloidal mercury for syphilis
• Importance of synthetic polymers

  Proteins are important natural colloids and are found in the body as components of muscle, bone and skin. The plasma proteins are responsible for binding certain drug molecules to such an extent that the pharmacologic activity of the drug is affected.
• Macromolecules used as adjuncts

  • Starch

  Cellulose
• Hydroxyethyl starch (HES)


  A macromolecule used as a plasma substitute
• Dextran


  Plasma expander
• Macromolecules used as coatings


  To protect drugs that are susceptible to atmospheric moisture or degradation under the acid conditions of the stomach
• Colloidal electrolytes (Surface-active agents)


  Used to increase the solubility, stability, and taste of certain compounds in aqueous and oily pharmaceutical preparations