33

Arthur J. Winfield

Introduction

Solutions are homogeneous mixtures of two or more components. They contain one or more solutes dissolved in one or more solvents, usually solids dissolved in liquids. The solvent is often aqueous but can be oily, alcoholic or some other solvent.

There are many types of pharmaceutical solutions. Solutions may be used as oral dosage forms, mouthwashes, gargles, nasal drops and ear drops and externally as lotions, liniments, paints, etc. Solutions may also be used in injections and ophthalmic preparations (see Chs 41, 42).

Solutions for oral dosage

Oral solutions are usually formulated so that the patient receives the usual dose of the medication in a conveniently administered volume, 5 mL or a multiple thereof, given to the patient using a 5 mL medicine spoon.

Advantages of solutions for oral use over a solid dosage form are that liquids are much easier to swallow than tablets or capsules and the medicament is readily absorbed from the gastrointestinal tract. Ease of taking is especially useful for children, elderly patients or those with chronic conditions such as Parkinson’s disease, who may have difficulty swallowing a solid oral dosage form. An advantage of solutions over suspensions is that the medicament is dispersed homogeneously throughout the preparation, without the need to shake the bottle. This makes the preparation easier for the patient to use and should ensure consistent dosage. Sometimes substances with a low aqueous solubility may be made into solution by the addition of another solvent rather than formulate the medicine as a suspension.

Disadvantages of solutions are that they are bulky, not convenient to carry around and less microbiologically and chemically stable than their solid counterparts. Oral solutions may have an unpleasant taste. The accuracy of oral dosage is dependent on the patient measuring the dose carefully.

The different forms of oral solutions are:

Solutions for other pharmaceutical uses

Topical solutions for external use are considered in Chapter 36. Some topical solutions are designed for use in body cavities, such as the nose, mouth and ear.

Expression of concentration

Strengths of pharmaceutical solutions can be expressed in a number of ways. The two most commonly used are in terms of amount of drug contained in 5 mL of vehicle or percentage strength (see Ch. 19).

Formulation of solutions

Solutions comprise the medicinal agent in a solvent as well as any additional agents. These additional agents are usually included to provide colour, flavour, sweetness or stability to the formulation. Most solutions are now manufactured on a large scale although it may be occasionally required to make up a solution extemporaneously. When compounding a solution, information on solubility and stability of each of the solutes must be taken into account.

Chemical and physical interactions that may take place between constituents must also be taken into account, as these will affect the preparation’s stability or potency. For example, esters of p-hydroxybenzoic acid, which can be used as preservatives in oral solutions, have a tendency to partition into certain flavouring oils. This could reduce the effective concentration of the preservative agent in the aqueous vehicle of the preparation to a level lower than that required for preservative action.

Oral syringes

If fractional doses are prescribed for oral liquids, they should not be diluted, but an oral syringe should be supplied with the dispensed oral liquid. The standard 5 mL or 10 mL capacity oral syringe is marked in 0.2 mL divisions to measure fractional doses. An adapter fits into the neck of all common sizes of the medicine bottle. Instructions should be supplied with the oral syringe: ‘Shake the bottle and then remove the lid and insert the adapter firmly into the top of the bottle. Push the tip of the oral syringe into the hole in the adapter and turn the bottle upside down. Pull the syringe plunger to draw liquid to the appropriate volume. It may be desirable to indicate this on the syringe. Turn the bottle right way up and carefully remove the syringe, holding the barrel. Gently put the tip into the child’s mouth to be inside the cheek. Slowly and gently push the plunger in and allow the child to swallow the medicine before removing the syringe. Do not squirt the liquid or direct it towards the throat. After completing the process, remove the adapter and replace the cap on the bottle. The adapter and syringe should be rinsed and left to dry’. Patient information leaflets are available to accompany the oral syringe.

Diluents

If a prescriber insists that a manufactured solution is diluted, then a suitable diluent must be selected. Information sources to obtain this information are the Medicines Compendium or the National Pharmaceutical Association (NPA) Diluent Directory. An indication of the expiry date for the diluted preparation is also given in these references. The dilution should be freshly prepared.

A short shelf-life for a diluted solution may require patients to return to the pharmacy to collect the balance of their medication. This may happen, for instance, where an oral sodium chloride solution has been prescribed for 1 month. The solution has a 2-week expiry, and must therefore be supplied in two instalments. The patient, or their representative, should be issued with an owing slip, or some similar documentation. This should state the name of the patient, the pharmacy, the item and quantity of medicine owed and the date of issue. A record should also be kept in the pharmacy. Most computer labelling systems have the facility to handle ‘owings’.

Traditionally used as an expectorant cough preparation but no longer recommended.

Formulation notes. Ammonium bicarbonate, ipecacuanha and camphor water are mild expectorants. Anise water acts as a mild expectorant and a flavouring agent. Liquid liquorice extract is used as a mild expectorant, flavouring and sweetening agent. Chloroform water acts as a sweetener and a preservative. Ammonium bicarbonate is soluble 1 in 5 of water, so will dissolve to give a solution. All other ingredients are liquids.

Method of preparation. Weigh the ammonium bicarbonate on a suitable balance and dissolve in approximately 15 mL water, in a 100 mL conical measure. Add the double strength chloroform water to this solution. Measure the other liquid ingredients and add to the solution. Make up to volume with water in the conical measure. Pack into an amber medicine bottle with a child-resistant closure. Polish the bottle and label, and provide a 5 mL spoon.

Shelf-life and storage. Store in a cool, dry place. It is recently prepared, therefore a shelf-life of 2–3 weeks is applicable.

Advice and labelling. ‘Shake well before use’. While this is not strictly required, it is good practice to include it.

Traditionally used as a cough suppressant in terminal care, no longer recommended.

Formulation notes. Oxymel is a solution of acetic acid, water and purified honey, used as a demulcent and sweetening agent in linctuses. Glycerol is also a demulcent and sweetener. Compound tartrazine solution is a colouring agent and syrup is a demulcent vehicle. Diamorphine is soluble 1 in 1.6 of water and 1 in 12 of alcohol, so a solution will be produced.

Method of preparation. Weigh 120 mg diamorphine on an appropriate balance. Transfer to a 200 mL measuring cylinder. Dissolve the diamorphine in the oxymel and glycerol. Add about 50 mL of syrup, then add the compound tartrazine solution. Transfer to a previously tared amber medicine bottle (see Ch. 32). Make up to volume with the syrup in the tared bottle in order to overcome difficulties in draining all the viscous mixture from a measure. Close with a child-resistant closure, polish and label the bottle and give a 5 mL medicine spoon or oral syringe with the medicine (depending on the dosage prescribed).

Shelf-life and storage. Store in a cool, dry place. It is recently prepared, therefore a shelf-life of 2–3 weeks is applicable.

Advice and labelling. ‘Shake well before use’. The linctus should be sipped and swallowed slowly, undiluted. ‘Warning. This medicine may make you sleepy. If this happens, do not drive or use tools or machines. Do not drink alcohol’ (BNF Label 2). Since this patient is terminally ill, they are unlikely to be driving or operating machinery so this part of the advisory label can be omitted. Alcohol should be avoided, as this will increase the sedative effect.

Action and uses. Traditionally used for short-term use in insomnia.

Formulation notes. Chloral hydrate is soluble 1 in 0.3 of water and has an unpleasant taste. Blackcurrant syrup is used as a flavouring agent to mask this.

Method of preparation. Weigh 2 g chloral hydrate on a suitable balance. Transfer it to a 50 mL measuring cylinder and dissolve it in water. Add the blackcurrant syrup. Add some of the syrup (rinsing the measure used for the blackcurrant syrup). Transfer the mixture to a tared, 50 mL amber medicine bottle and make up to volume, to avoid loss of the viscous product in the measures. Polish and label the bottle and give a 5 mL medicine spoon or oral syringe with the medicine.

Shelf-life and storage. Store in a cool, dry place. Chloral hydrate is volatile and sensitive to light. It is recently prepared and a shelf life of 2–3 weeks is appropriate.

Advice and labelling. ‘Shake well before use’ and BNF Labels 1 and 27. An appropriate dose for a child up to 1 year is one 5 mL spoonful to be given, well diluted with water, at bedtime. The parent should be advised that this might make the child drowsy.

Traditionally used for the alkalinization of urine to relieve discomfort in mild urinary tract infections or cystitis.

Formulation notes. Citric acid and potassium citrate are the active ingredients; both are soluble 1 in 1 of water. Lemon spirit, which is lemon oil in alcoholic solution, is a flavouring agent. The oil tends to be displaced from solution in an aqueous medium, especially in the presence of a high concentration of salts. The quillaia tincture is a surfactant used to emulsify any displaced lemon oil. Syrup is a sweetening agent.

Method of preparation. The solids should be size reduced, weighed and dissolved in the double strength chloroform water and syrup. The quillaia tincture should be added before the lemon spirit is added with stirring, so that immediate emulsification of the oil will be achieved if required. Make up to volume with water. Pack in an amber medicine bottle with a child-resistant closure. Polish and label the bottle and give a 5 mL medicine spoon with the medicine.

Shelf-life and storage. Store in a cool, dry place. It is recently prepared, therefore a shelf-life of 2–3 weeks is applicable.

Advice and labelling. ‘Shake well before use’. The medicine should be diluted with plenty of water (BNF Label 27).

Action and uses. Mechanically cleans and freshens the mouth.

Formulation notes. Concentrated peppermint emulsion is used as a flavouring and the chloroform water is a sweetener and preservative. Sodium chloride is soluble 1 in 3 of water and sodium bicarbonate is soluble 1 in 11 of water.

Method of preparation. The solids are weighed on a suitable balance and dissolved in a 500 mL conical measure in approximately 100 mL of water. Add the double strength chloroform water and the concentrated peppermint emulsion. Make up to volume with water. Pack in an amber bottle with a child-resistant closure. Polish and label the bottle.

Shelf-life and storage. Store in a cool, dry place. It is recently prepared, therefore a shelf-life of 2–3 weeks is applicable.

Advice and labelling. ‘Shake well before use’. The patient should be directed to use about 15 mL diluted in an equal volume of warm water, usually morning and night, unless otherwise directed. The solution should be used as a mouthwash and should not be swallowed, although reassure the patient that it is not harmful to swallow small amounts of the mouthwash.

Action and uses. For the softening and removal of earwax (usually prior to syringing with warm water).

Formulation notes. Sodium bicarbonate is soluble 1 in 11 of water. Glycerol is a viscous liquid used to thicken the drops, but presents problems in measuring the volume accurately.

Method of preparation. Weigh 500 mg sodium bicarbonate and dissolve in 6 mL of water, using a 10 mL conical measure. Carefully make up to 7 mL using water. Carefully add glycerol up to the 10 mL mark (this will result in 3 mL of glycerol being added to the solution). Pack in a 10 mL hexagonal, amber, ribbed bottle with a dropper. Polish and label the bottle on the three smooth sides.

Shelf-life and storage. Store in a cool, dry place. The drops are recently prepared, therefore a shelf-life of 2–3 weeks is applicable.

Advice and labelling. ‘Shake well before use’ and ‘Not to be taken’. The bottle may be warmed in the hands before placing drops in the ears. A patient information leaflet should be used to describe how to use the drops (see Fig. 33.1).

Key Points