Solutions Flashcards
what is a solution
a homogenous one-phase system consisting of two or more components
solvent
phase in which the dispersion occurs
solute
the component which is dispersed as small molecules or ions in the solvent
types of solution
aqueous or non-aqueous
advantage of solutions as oral dosage form
- easy to swallow (peds)
- drug immediately available for absorption
- uniform distribution
- less irritation than capsules
disadvantage of solutions as oral dosage form
- bulky and inconvenient to transport or store
- poor stability (esp if drug susceptible to hydrolysis)
- prone to microbial growth/ contamination
- unpleasant taste of drug
types of preparations to be made
- potable water
- purified water BP
- water for injection BP
- water free from carbon dioxide or air
cosolvency
solubility of a weak electrolyte or non-polar compound in water can be improved by the addition of a water-miscible solvent in which the compound is also soluble
what are cosolvents
vehicles used in combination to increase the solubility of a drug
what is the solubility of a drug affected by
dielectric constant of solvent system, ideally dielectric constant should be 25-80
pH control
if drug is either a weak acid/base, its degree of ionisation and consequently its solubility are influenced by the pH of the solubility, ensure pH does not conflict with other product requirement
solubilization
concentration of surfactant used should be above its critical micellar concentration- micellar solubilization
what is the range of values for hydrophilic surfactant to be a useful solubilising agent
above 15 HLB value
how can solubility be improved
adding surfactant, however a large excess of surfactant is undesirable
factors that affect choice of solubilising agents
- toxicity and irritancy
- miscibility with solvent system
- compatibility with other components
- odour and taste
example of solutions with solubilising agents
- fat soluble vitamins + polysorbates
- iodine + macrogol ethers
- steroids + polyoxyethylated castor oil
- cresol + chloroxylenol + potassium soap of fatty acids
example of combi of cosolvent and solubilising agents employed to improve solubility
- vitamin A + polysorbate 80 + glycerol
2. chloroxylenol + potassium ricinoleate + ethanol terpineol
chemical modification
involves synthesis of soluble salts of the drug; soluble salt which may not have any activity is converted back to active base in biological system
example of chemical modification
- sodium phosphate salts of hydrocortisone, prednisolone, and betamethasone
- sodium succinate salt of chloramphenicol
particle size reduction
size and shape of very small particles (< 1 micron) can affect their solubility, but less commonly employed to improve solubility
how are particle size commonly reduced
milling
non-aqueous solutions
solvents are classified as
- fixed oils of vegetable origin,
- alcohols,
- polyhydric alcohols,
- mineral oils
- and others
why are non-aq solution employed
- prepare solution of drugs which are unstable in water
2. prepare intramuscular injections of drugs for depot therapy
alcohol for external use only
- industrial methylated spirit (ethanol with 5% methanol as denaturant)
- isopropanol
alcohol
commonly employed in low concentration, as a cosolvent with water in the formulation of aqueous solution for oral and parenteral use
polyhydric alcohols
commonly used as cosolvent with water in the formulation of injections
example of polyhydric alcohol
- glycercol (E & I): phenol ear drops BPC 1973
- propylene glycol (E & I): Digoxin injection BP, Phenobarbitone Injection BP, Chloramphenicol Ear Drops BP
- Polyethylene glycols of low MR (E&I): Erythromycin Ethylsuccinate injection BP
- Dipropylene Glycol, Diethylene glycol, Ethylene glycol (E only cause toxic): veterinary and horticultural use
Mineral oils
internal external use, limited use as solvent in pharma preparation due to oily tacky nature; veg oil preferred; more often used in formulation of emulsion
what are not for internal use
- xylene (eardrops)
- ethyl ether (cosolvent with OH in collodions, extraction of crude drug)
- isopropyl myristate, isopropyl palmitate (cosmetics)
- dimethylsulphoxide, dimethylformamide, dimethylacetamide (veterinary)
- kerosene (insecticides)
buffers
employed to resist any change in pH when acid/alkali added
example of buffers
carbonates, citrates, gluconates, lactates, phosphates, tartrates, borates
color
employ to improve attractiveness and enable easy identification of products
how may stability of color be affected by
pH, ultraviolet radiation, presence of oxidizing or reducin agents
types of colors
- natural: show variation in chemical composition and are less stable, but more widely accepted (carotenoids, chlorophylls, anthocyanins)
- synthetic: coal tar dyes, brighter n=more stable colors (sodium salts of sulphonic acids)
natural sweetening agent
sucrose, fructose, sorbitol, mannitol, glycerol, xylitol, hydrogenated glucose syrup, isomalt, honey , liquorice
artificial sweetening agent
intensify sweeteners (<0.2%); tendency to impart bitter/ metallic after taste eg: saccharin, aspartame, acesulfame, potassium, thaumatin
flavours
employed to make oral products more palatable while fragrances improve the appeal of the product
eg of flavor/fragrance
fruit juice, aromatic oils, herbs, spices
preservative
prevent microbial contamination of product
antioxidants
prevents degradation of compounds by oxidation
isotonicity modifiers
adjust tonicity of large volume solutions for parenteral and ophthalmic use
density modifiers
to adjust the density of spinal anaesthetics
how are pharmaceutical solutions manufactured
mixers: propeller, turbine, paddle
how are pharmaceutical solutions evaluated for quality
drug content, density, tonixity, viscoxity (topical), clarity/particulate, color, sterility (parental/opth)
