PS 5 E

• types of solutions


  oral solutions (aqueous, syrups, elixirs, tinctures), topical solutions (washes, applications, sprays), wound cleaners and antiseptics, ophthalmic solutions (eye drops, ear washes), otic solutions (ear drops, ear washes), nasal solutions (nasal drops, nasal sprays), mouthwashes, gargle and mouth/throat sprays, nebuliser solutions for inhalation, parenteral solutions (injections and infusions), vaginal solutions (douches), rectal solutions (enemas)
• oral solutions


  pH 5-8 typically. aqueous, syrup/linctus (contain lots of sugar + water, thicker, viscous), elixir (water + ethanol improves solubility can be sweetened and flavoured) - not for kids, sleepiness? , tinctures (extract of vegetable matter or drug substance pure drug substance, ethanol or ethanol + water solute) - on the skin
• common solvents in solutions

  water, ethanol, glycerol, propylene glycol, PEG 400, vegetable oils (olive, corn, sesame, castor), and paraffin oil. depends on drug and the use for the drug product. oral predominantly water
• solution categories


  aqueous, alcoholic, oily
• excipients in solutions/suspensions


  buffers: acetic acid + Na acetate. Isotonicity modifiers (non-oral): glucose, NaCl. Viscosity modifiers/thickeners: glycerol + sucrose + polyethylene glycol. suspending agents: vegetable gums and cellulose derivatives. antioxidants: ascorbic acid. antimicrobial preservatives: benzoic acid and sodium benzoate. sweeteners: sugar alcohols (mannitol) and artificial sweeteners (saccharin), colourants, flavourings
• flavourings for medicines


  masking salty: cinnamon, orange. bitter: cocoa, tutti frutti. very sweet: fruit, berry. sour/acidic: citrus, cherry. oily: wintergreen, lemon. metallic: mint, marshmallow
• manufacture of solutions


  stepwise addition of solutes to solvents (in particular order), mixing, blending/agitation, and careful warming (if needed) to facilitate dissolution. filtration, QC testing (appearance, viscosity, pH, identity of actives, potency, preservative concentration and efficacy) packaging and labelling. some are prepared as powders to be rehydrated.
• powder to solutions


  some are prepared as powders to be rehydrated, rehydration solutions, enemas, vaginal douches, powders for reconstitution and injection/infusion
• packaging for solutions


  non-injectables: bottles, spray bottles: glass/plastic, child-resistant closures. injectables: ampoules, vials, prefilled syringes: glass, plastic polymeric stoppers/plunger seals
• advantages of oral solutions

  homogeneous dispersal (don't need to shake), drug already in solution, ready for delivery and rapid absorption, easy to administer and swallow (if good taste and smell), easy to make palatable (flavours and sweeteners), easy to measure required dose, easy dose adjustment, good for paediatric and elderly patients and swallowing difficulties
• disadvantages of oral solutions

  not all drugs are adequately soluble to formulate as solutions (suspensions potentially), taste/smell bad, potential degradation of the drug (hydrolysis and or oxidation), potential Microbial growth, potential allergies to preservatives, potential crystallisation/precipitation of some drug substances in cold conditions. shorter shelf life than solid dosage forms, requires a measuring device, easy to make mistakes in measuring and dispensing, bulky and less convenient to transport and store, potential breakage of glass containers
• solution definition


  a thermodynamically stable, one-phase, homogeneous system, composed of two or more components, one of which is completely dissolved in the other.
• solubility definition


  the quantity of that substance that can be maintained in solution in a given solvent at a given temperature and pressure. typically expressed as mL that can dissolve in 1 gram or grams that can dissolve in 1 L of solution
• saturated solution


  a solution that contains the maximum amount of solute that the solvent will accommodate at room temperature and pressure.
• supersaturated solution


  contains a larger amount of solute than the solvent can normally accommodate at a certain temperature. it is therefore unstable and the solute will normally crystallise/precipitate out
• concentration


  the measure of the relative amounts of substances making a solution. concentration is typically expressed as unit mass of solute per unit volume of solution g/ml or g/cm^3. other expressions %w/v (grams of solute in 100mL of solution), %w/w (grams of solute in 100mL solvent) %v/v (mL of solute in 100mL of solution) + ppm
• dissolution


  the transfer of molecules or ions from a solid state into a solution. molecules are removed from their crystal arrangement and cavities for the solute molecule are created in the solvent (takes energy), the solute molecules are inserted into cavities (releases energy). the particles of the solute are surrounded by a diffusion layer Cs, which the solute diffuses out of into the bulk solvent conc C. Agitation clears the diffusion layer and increases the rate of dissolution
• noyes-Whitney equation


  dC/dt (rate of diffusion of drug particles) = D x A(Cs-C) / h . D- diffusion coefficient of the drug in soltuon in gastrointestinal fluids. A - surface area of the drug particles in contact with fluids. h thickness of diffusion layer around each drug particle. Cs - the saturation solubility of the drug in solution in the diffusion layer. C The concentration of the drug in the gastrointestinal fluids
• solubility depends on 


  hydrophilicity and hydrophobicity, polarity, ionisability, molecular size, crystallinity, solvent-solute interactions, temperature, and interactions with other solutes.
• increasing solubility


  amporphouse, adding organic co-solvents, surfactants to produce micelles, converting a weak acid or base drug to a salt, changing pH of the vehicle to increase ionisation or weak acid or weak base drug. micronising the drug to increase surface area and increase rate of dissolution and solubility to some extent.
• increasing rate of dissolution

  micronising drug to increase its surface area. rapidly stirring the mixture to reduce the thickness of the diffusion layer. warming the liquid. dissolving the drug in the solvent in which it is most soluble before adding other co-solvents and or solutes
• types of surfactants


  form micelles, ( ionic, nonionic and mixed) which allow hydrophobic drugs to enter solution
• cyclodextrins


  sugar molecules in a tube shape, with a hydrophobic cavity that drugs can fit into. have different sizes and are highly water soluble
• common ion effect


  the ionisation of a substance is depressed by the presence of more of the ion form. this pushes the equilibrium of the solution toward the solid form and there will be poor solubility
• colligative properties


  dissolving a solute in a solvent affects several properties: lowers vapour pressure, lowers freezing point, raises boiling point, and establishes tonicity and osmotic pressure of the liquid. the magnitude of the changes depend upon the total number of moles of solute and solvent
• osmosis and osmolality


  the movement of water from areas of high concentration to areas of low concentration. the rate and extent of osmosis that will occur depends upon the difference in osmolarity between solutions on either side of the membrane. osmolarity is the total concentration of all solutions in a solution as moles per liter
• calculate osmolarity


  calculate the conc of each solvent in millimoles per litre mmol/L. count each non-dissociated molecule as 1 unit and count each separate ion from an ionised compound as 1 unit. add the concentrations of each solute molecule and ion together, this sum is the osmolarity.
• tonicity


  the ability of an extracellular solution to make water move into or out of a cell by osmosis. hypotonic, isotonic (when solutions have same or similar osmolality) and hypertonic
• freezing point depression


  dissolution of solutes in water results in depression of freezing point of the resulting solution. the FPD of a 1 molar solution of solute is -1.86 C vs 0.0 C. FPD is directly proportional to the total concentration of solutes (ionised and unionised).
• cells particularly vulnerable to tonicity

  blood cells, muscle cells, eyes, nasal passages, lung tissues, vaginal, rectal and intestinal mucosa, and open wounds. also require a pH close to the physiological pH