liquid comped

• Liquid Dosage Forms in Pharmaceuticals


  • Syrup
  • Oral Suspension
  • Oral Solution
  • Oral Drop
  • Oral Emulsion
  • Mixture
  • Linctuse
  • Elixir
• Scenarios regarding the formulation of pharmaceutical solutions of a therapeutic agent for oral administration

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


  1. Removal of a molecule of the drug from the solid state

  2. Formation of a cavity within the solvent

  3. Accommodation of the drug molecule into the 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 the solubility of therapeutic agents

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

  Inversely related to solubility
• Chemical substituent groups and substituent position

  Directly affect the solubility of the therapeutic agent
• Degree of ionisation


  Affects the solubility of acidic and basic compounds
• Buffer


  Used to control the pH of the formulation without adversely affecting the solubility of the therapeutic agent
• Co-solvents


  Liquid components incorporated into a formulation to enhance the solubility of poorly soluble drugs to the required level
• Commonly employed co-solvents


  • Glycerol
  • Propylene glycol
  • Ethanol
  • Poly(ethylene glycol)
• Excipients


  Physiologically inert compounds that facilitate the administration of the dosage form, protect the formulation from issues regarding physical and chemical stability, and enhance the solubility of the therapeutic agent
• Purified Water USP


  Most commonly used vehicle in solutions for oral administration, prepared by distillation, ion exchange methods or by reverse osmosis, with a solid residue (obtained after evaporation) of less than 1 mg per 100 ml of evaporated sample, not to be used for the preparation of parenteral formulations
• Main co-solvents used in the formulation of oral solutions

  • Glycerol
  • Alcohol USP (ethanol)
  • Propylene Glycol USP
  • Poly(ethylene glycol) (PEG)
• Surface-active agents


  Chemicals that possess both hydrophilic (water-liking) and hydrophobic (water-disliking) regions
• Drug-polymer complex would prevent drug absorption across biological membranes
• Buffers used in pharmaceutical solutions

  • Acetates (acetic acid and sodium acetate)
  • Citrates (citric acid and sodium citrate)
  • Phosphates (sodium phosphate and disodium phosphate)
• Sweetening agents employed in liquid formulations designed for oral administration

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


  Non-ionic (neutral) polymers and ionic polymers used to increase and control the viscosity of pharmaceutical solutions
• Non-ionic (neutral) polymers


  • Methylcellulose
  • Hydroxyethylcellulose
  • Hydroxypropylcellulose
  • Polyvinylpyrrolidone
• Ionic polymers


  • Sodium carboxymethylcellulose (anionic)
  • Sodium alginate (anionic)
• Antioxidants


  • Sodium sulphite
  • Sodium metabisulphite
  • Sodium formaldehyde sulphoxylate
  • Ascorbic acid
  • Butylated hydroxytoluene (BHT)
  • Butylated hydroxyanisole (BHA)
  • Propyl gallate
• Preservatives used in pharmaceutical solutions for oral use

  • Benzoic acid and salts (0.1-0.3%)
  • Sorbic acid and its salts (0.05-0.2%)
  • Alkyl esters of parahydroxybenzoic acid (0.001-0.2%)
• Linctuses


  Viscous preparations that contain the therapeutic agent dissolved in a vehicle composed of a high percentage of sucrose and, if required, other sweetening agents
• Quality control tests for liquid preparations


  • Evaluation for visual appearance, colour, taste, odour, labelling, and homogeneity
  • Assay of active ingredients and of degradation products
  • Pourability
  • Viscosity
  • Isotonicity
  • Particle size agglomeration and particle size distribution
  • Clarity
  • Crystallization and precipitation
  • Gas evolution
  • Relative density
  • pH
  • Surface tension
  • Microbial limit tests
  • Stability of the 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 test and particulate matter testing are necessary as additional tests
• Saccharin sodium


  used either as the sole sweetening agent or in combination with sugars or sorbitol to reduce the sugar concentration in the formulation.
• Poly(ethylene glycol) (PEG)


  is a polymer composed of repeating units of the monomer ethylene oxide, Lower-molecular-weight grades (PEG 200, PEG 400) are preferred as co-solvents in pharmaceutical solutions
• Propylene Glycol USP


  an odourless, colourless, viscous liquid diol that contains two hydroxyl

  groups. It is used in pharmaceutical preparations as a co-solvent, generally as a replacement for glycerin.
• Alcohol USP (CH3CH2OH)


  contains between 94.9 and 96.0% v/v ethyl alcohol (ethanol) and is commonly used as a co-solvent, both as a single co-solvent and with other co-solvents, e.g. glycerol
• Glycerol


  (also termed glycerin) is an odorless, sweet liquid that is miscible with water and whose co-solvency properties are due to the presence of three hydroxyl groups (termed a triol). It has similar co-solvency properties to ethanol.
• Sweetening agents


  are employed in liquid formulations designed for oral administration specifically to increase the palatability of the therapeutic agent.
• increasing the viscosity of some formulations may increase the

  palatability.
• The viscosity of pharmaceutical solutions may be easily increased (and controlled) by the addition of non-ionic or ionic hydrophilic polymers.
• Antioxidant


  molecules that are redox systems that exhibit higher oxidative potential

  than the therapeutic agent or, alternatively, are compounds that inhibit free radical-induced drug decomposition.
• Preservatives


  are included in pharmaceutical solutions to control the microbial bioburden of the formulation.
• Flavours


  These are employed whenever the unpalatable taste of a therapeutic agent is apparent, even in the presence of the sweetening agents.
• Colours


  These are generally natural or synthetic water soluble, photo-stable ingredients that are selected according to the flavour of the preparation.