Solutions 1 Flashcards
What are solutions? What are its advantages and disadvantages
Liquid preparations that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents
advantages
- Faster absorption than other formulations
- Flexible dosing
- Multiple routes of administration possible
- Homogeneous = dose uniformity
- Simple to prepare
- Facilitate swallowing when administered orally
- May be used to minimise adverse effects
disadvantages
- Potentially reduced stability
- Taste is more pronounced (oral)
- Bulky
- Many drugs poorly water soluble
- Accuracy in measurement of oral dose is patient dependent
- Measuring device needs to be supplied
Discuss the preparation of pharmaceutical solutions.
Preparation
Solute(s) added to the solvent and stirred until dissolution is complete.
To aid dissolution:
- Heat (if heat stable)
- Reducing particle size
- Solubilising agents
- Agitation
Filtration is required to ensure clarity of the final solution “pharmaceutically elegant” product.
- Solutions must retain their initial clarity, odour, taste and viscosity over the product shelf-life
Discuss the formulation principles of pharmaceutical solutions.
When formulating pharmaceutical solutions it is important to consider
- Solubility of drug – formulate well within solubility
- Stability of drug
Other agents (excipients) that may be included in the formulation of solutions include:
- Agents to increase solubility e.g. surfactants
- Agents to increase elegance and function e.g. colour, flavour, sweeteners, perfumes, viscosity enhancers.
- Agents to increase stability e.g. stabilisers, preservatives
What are excipients
Must be non-toxic, non-irritating, non-sensitising and compatible with other ingredients
Solubility enhancers (surfactants, cyclodextrins, cosolvents)
Stability enchancers
- Preservatives (increase shelf life, common ones are benzoic acid, chlorocresol, chlorbutatnol)
- Buffers e.g. citrate buffers
- Antioxidants and chelating agents
Elegance and function
- Viscosity Enhancers e.g. glucose
- Tonicity Modifiers (sodium chloride, glucose) –> solutions for injection, application to mucuous membrane must be made isotonic with blood/tissue fluid to avoid pain and irritiation
- Colouring agents
- Flavouring & sweetening agents
- Perfumes
Describe water as a solvent, its advantages and disadvantages
- For manufactured and compounded nonsterile preparations Purified water BP (fbc) or Water for Irrigation should be used. For parenteral solutions Water for Injections pyrogen-free (fever free) and sterile.
advantages
- Economical
- Stable and inert – physically, chemically, pharmacologically
- Non-toxic and non-irritant – suitable for IV
- Colourless, odourless and tasteless
- Wide solvent action, miscible with other solvents
- Non-flammable – no storage issues
- Neutral pH
- Low viscosity
disadvantages
- Not selective – dissolves many substances
- Growth medium for micro-organisms (fungi and bacteria) – preservative required
- Promotes degradation by hydrolysis
- High boiling point
- greater energy requirements
What are co-solvents
Lower polarity solvents that are miscible with water eg ethanol, glycerol, propylene glycol, polyethylene glycol 400 (PEG 400).
- Co-solvent systems are composed of water/water-miscible solvents.
- They create exponential increases in solubility of weak electrolytes and non-polar molecules.
- Co-solvents decrease interfacial tension or alter the dielectric constant of the solvent.
- Example: Paracetamol (sparingly soluble) Elixir CF APF15, ethanol 90%, propylene glycol & water
Describe ethanol as a solvent/co-solvent/vehicle and describe its advantages and disadvantages
Widely used in pharmaceutical formulations and cosmetics as a solvent and vehicle (external use), as a co-solvent (internal).
- Good solvent for non-water soluble ingredients
- Uses: solvent , penetration enhancer for topical preparations, preservative, disinfectant
Advantages
- Dissolves many organic substances eg volatile oils, alkaloids and their salts
- Fairly selective for synthetic organic drugs
- Has preservative action
- Non-toxic at low concentrations
- Neutral
- Colourless
- Miscible with water
- Less energy required – lower bp than water
Disadvantages
- Expensive Toxic in high concentrations – pharmacological effect
- Cannot usually be injected IV
- Volatile
- Flammable
Un-denatured spirits must be used when alcohol is required for internal preparations. E95 and E96
> IMS, SVI can prepare external formulations but NOT internal
Describe glycerol, its advantages and disadvantages
Colourless, odourless, viscous liquid with a sweet taste (~0.6 times as sweet as sucrose).
- Polar solvent, miscible with water and ethanol
- Used widely in pharmaceutical formulations
- Therapeutic: demulcent, osmotic laxative
- Topical formulations: solvent, humectant
- oral formulations: solvent, sweetening agent, preservative
Advantages
- Excellent solvent for alkaloids, tannins, phenol
- Less selective than ethanol
- Relatively inexpensive
- Very viscous – suitable vehicle for throat paints and some external preparations
- Preservative action at high concentration
- Non-flammable
- Sweet taste – useful for oral preparations
Disadvantages: Osmotic effects can cause irritation to mucous membranes
What is propylene glycol (internal or external) and what are its uses
Odourless, colourless, viscous liquid with a slightly sweet taste.
- Good solvent
- Commonly found in formulations of nasal preparations to increase the viscosity and thus prolong contact time.
- Uses: Humectant ~15% Preservative ~15-30% Solvent or co-solvent 5-80% depending on dosage form
What are aromatic waters (internal or external)?
- Clear saturated aqueous solutions of volatile/essential oils (e.g. rose oil) or other aromatic or volatile substances.
- Usually prepared by diluting the concentrated water with 39 times its volume of purified water (fbc).
- Uses: flavours, perfumes, carminatives and astringents
What are syrups (internal) and what is its use?
Concentrated solutions of sucrose or other sugars to which medicaments or flavouring agents are often added.
Uses: Sweetening, flavouring and demulcent(relieve inflammation)
- Soothing effects on mm e.g. throat
- Comon sweetener but over long term can lead to dental caries
- Visocity enhancer –> prolongs contact time with mucous membranes
What are some examples of syrups?
SYRUP BP/APF
Prepared with the aid of heat and agitation.
- Microbial growth in syrups containing >65%w/w sucrose is usually retarded due to osmotic effects.10
- Overheating Syrup BP/APF causes inversion to dextrose and fructose –> darkening of colour and susceptibility to microbial contamination.
Flavoured syrups - used as flavouring and sweetening agents for oral solutions ~10-20%
- eg Raspberry Syrup, Orange Syrup, Lemon Syrup
- Be mindful of pH of some flavouring syrups
- Sugar may crystallise out from formulations containing high concentration of sucrose
What are some exmaple of vehicles (sorbitol solution –> external and internal + diabetic syrups –> internal)
Sorbitol Solution BPC (Sorbitol liquid) (internal and external)
- Colourless, odourless, syrupy liquid with a sweetish taste, soluble in water, contains 70%w/w of total solids, mainly of D-sorbitol.
Uses:
- Therapeutic: osmotic laxative
- Topical formulations - humectant
- Oral formulations –> Vehicle + Sweetening agent + Prevent crystallisation of sugars in syrups ~15-30% (sorbitol powder)
Diabetic syrups (internal)
Do not contain sugar, use artificial/synthetic sweeteners e.g. saccharin sodium (300-550x sweeter than sugar)
- Ingredients added to water to produce a preparation that is similar to syrup.
- Thickening agents are added to increase the viscosity e.g. acacia, tragacanth and preservatives are added.
