MIDTERM (LIQUIDS)

• Oral Liquid Dosage Forms in Pharmaceuticals

  • Syrup
  • Oral Suspension
  • Oral Solution
  • Oral Drop
  • Oral Emulsion
  • Mixture
  • Linctuse
  • Elixir
• Homogeneous


  (in pharmaceutical solutions) the therapeutic agent and the excipients are legally required to be present in solution over the shelf-life of the formulated product
• Challenges to pharmaceutical scientist

  • Attainment of homogeneity in the formulation, due primarily to the limited aqueous solubility of the therapeutic agent
• Possible scenarios regarding the formulation of pharmaceutical solutions

  • Aqueous solubility of therapeutic agent is high at selected pH
  • Aqueous solubility of therapeutic agent is moderate at selected pH
  • Aqueous solubility of therapeutic agent is low at selected pH
• Drug dissolution

  1. Removal of drug molecule from solid state

  2. Formation of cavity within solvent

  3. Accommodation of drug molecule into formed cavity
• Gibb's free energy


  Thermodynamic potential that measures the maximum amount of reversible work that can be performed by a thermodynamic system at constant temperature and pressure
• Enthalpy


  Thermodynamic capacity of API
• Entropy


  Measurement of the degree of randomness or spontaneity of API
• Factors affecting solubility of therapeutic agents

  • Molecular weight
  • Volume
  • Radius of gyration
  • Density
  • Number of rotatable bonds
  • Hydrogen bond donors and acceptors
• Melting point of therapeutic agent

  Inversely related to solubility
• Chemical substituent groups and position

  Directly affect solubility of therapeutic agent
• Degree of ionisation


  Affects solubility of acidic and basic compounds
• Buffer


  Used to control pH of formulation and optimise physicochemical performance
• Examples of buffer salts

  • Acetates
  • Citrates
  • Phosphates
• Sweetening agents


  Employed to increase palatability of therapeutic agent in oral preparations
• Main sweetening agents

  • Sucrose
  • Liquid glucose
  • Glycerol
  • Sorbitol
  • Saccharin sodium
  • Aspartame
• Viscosity-enhancing agents


  Used to increase viscosity and palatability of formulations
• Non-ionic viscosity-enhancing polymers

  • Methylcellulose
  • Hydroxyethylcellulose
  • Hydroxypropylcellulose
  • Polyvinylpyrrolidone
• Ionic viscosity-enhancing polymers

  • Sodium carboxymethylcellulose
  • Sodium alginate
• Antioxidants


  Molecules that exhibit higher oxidative potential than the therapeutic agent or inhibit free radical-induced drug decomposition
• Examples of water-soluble antioxidants

  • Sodium sulphite
  • Sodium metabisulphite
  • Sodium formaldehyde sulphoxylate
  • Ascorbic acid
• Examples of oil-based antioxidants

  • Butylated hydroxytoluene (BHT)
  • Butylated hydroxyanisole (BHA)
  • Propyl gallate
• Ideal properties of preservatives

  • Possess broad spectrum antimicrobial activity
  • Be chemically and physically stable over shelf-life
  • Have low toxicity
• Examples of preservatives used in oral solutions

  • Benzoic acid and salts
  • Sorbic acid and salts
  • Alkyl esters of parahydroxybenzoic acid
• Flavours


  Employed to mask unpalatable taste of therapeutic agent
• Colours


  Water soluble, photo-stable ingredients selected according to flavour of preparation
• Linctuses


  Viscous preparations containing therapeutic agent dissolved in vehicle composed of high percentage of sucrose and other sweetening agents
• Quality control tests for liquid preparations


  • Evaluation of visual appearance, colour, taste, odour, labelling, and homogeneity
  • Assay of active ingredients and degradation products
  • Pourability
  • Viscosity
  • Isotonicity
  • Particle size, agglomeration and distribution
  • Clarity
  • Crystallization and precipitation
  • Gas evolution
  • Relative density
  • pH
  • Surface tension
  • Microbial limit tests
  • Stability of active ingredient(s) and identification tests
  • Light stability
  • Container and closure compatibility
  • Redispersibility
  • Suspensibility
  • Storage condition
• For liquid products to be used as injections, eye drops or vaccines, sterility, apyrogenicity and particulate matter testing are necessary as additional tests