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6
Solutions
Introduction and overview 101 Gargles and mouthwashes 105
General principles of solution preparation 103 Enemas and douches 105
Solubility 103 External solutions 105
Stability 103 Lotions 105
General method 103 Liniments 105
Oral solutions 104 Applications 105
Elixirs 104 Collodions 106
Linctuses 105 Worked examples 106
Syrups 105 Summaryofessential principles relating
Mixtures 105 to solutions 112
Draughts 105 Packaging 112
Spirits 105 Discard dates 112
Paediatric drops 105 Labelling 113
Introduction and overview Essentially a solution is a homogeneous liquid
preparation that contains one or more dissolved med-
Solutionsareoneoftheoldestdosageformsusedinthe icaments. Since, by definition, active ingredients are
treatment of patients and afford rapid and high dissolved within the vehicle, uniform doses by volume
absorption of soluble medicinal products. Therefore, may be obtained without any need to shake the for-
the compounding of solutions retains an important mulation. This is an advantage over some other for-
place in therapeutics today. Owing to the simplicity mulation types (e.g. suspensions, see Chapter 7).
and hence the speed of preparation of an ad hoc for- In general, water is chosen as the vehicle in which
mulation, they are of particular use for individuals medicaments are dissolved, as it is non-toxic, non-
whohavedifficulty in swallowing solid dosage forms irritant, tasteless, relatively cheap, and many drugs
(for example paediatric, geriatric, intensive care and are water soluble. Problems may be encountered
psychiatric patients), where compliance needs to be where active drugs are not particularly water soluble
checked on administration (for example in prisons or orsuffer from hydrolysis in aqueous solution. In these
psychiatricpharmacy)andincaseswhereprecise,indi- casesitisoftenpossibletoformulateavehiclecontain-
vidualised dosages are required. ing water mixed with a variety of other solvents.
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102 | Pharmaceutical forms and their preparation
In the British Pharmacopoeia (BP), oral solutions * Itis difficult to mask unpleasant tastes. Although
are defined as ‘Oral Liquids containing one or more liquid dosage forms may be ideal for small
active ingredients dissolved in a suitable vehicle’. children who are unable to swallow solid dosage
Solutions provide a number of distinct advantages forms, many drugs taste unpleasant when
anddisadvantagescomparedwithotherdosageforms. formulatedintoasolution.Itispossibletoattempt
The advantages of solutions as pharmaceutical pro- to maskanyunpleasanttastesbytheadditionofa
ducts are that: flavouring, but this will not always be successful.
* Theyarebulky,difficulttotransportandproneto
* Thedrugisimmediately available for absorption. breakages. A major disadvantage of all liquid
Whensoliddosageformsaretakenorally,thedrug dosage forms is that they are always much larger
needs to dissolve before absorption into the body and more bulky than their comparable solid
cantakeplace.Byprovidingthedruginasolution, formulation. This makes them heavier and more
the dissolution phase of the absorption process can difficult to transport. Coupled with this is the fact
be bypassed, providing quicker absorption. that, traditionally, pharmaceutical liquids are
* Flexible dosing is possible. The active ingredient packedinglassbottles.Theseareobviouslyprone
within the solution will be present in a certain tobreakagewhichcanbehazardousandcausethe
concentrationperunitvolume.Ifalterationstothe loss of the preparation.
quantity of active ingredient to be administered * Technicalaccuracyisneededtomeasurethedose
are required, a simple alteration to the quantity of onadministration. Although the dose can be
solution to be taken is all that is required. titrated without the need to produce additional
* Theymaybedesignedforanyrouteofabsorption. preparations (see point 2 from the advantages
Althoughwhendiscussingsolutionstheoralroute above), patient accuracy in measuring a dose is
of administration is often considered, solutions required. It is accepted that patients’ abilities to
canbeadministeredviaanumberofotherroutes. measure an accurate dose can vary considerably
Parenteral preparations (injections), enemas for andthisneedstobetakenintoconsiderationwhen
rectal use, topical (for use on the skin) preparing a liquid preparation. This is especially
preparations and ophthalmic preparations can important when the volume of liquid to be
all be solutions. administeredisverysmall,wheresmallchangesin
* Thereisnoneedtoshakethecontainer. Unlike the volume administered may result in large
someliquidpreparations(e.g.suspensions),asthe increases or decreases in dose.
active ingredient is dissolved within the vehicle * Somedrugsarepoorlysoluble.Thesolubilityofa
there is no need to shake the container to ensure a drug needs to be taken into consideration when
uniform dose is measured. preparing a solution to ensure that the final
* Theyfacilitateswallowingindifficultcases.Some volumeproducedisnotexcessive.Insomecasesit
patients may find it hard to swallow traditional maybenecessarytoalterthevehicleordrugform
solid dosage forms (e.g. infants or the elderly). In (for example the free alkaloid or its salt) in order
these situations, it may be easier for the patient to to be able to formulate a convenient preparation.
take a liquid dosage form. * Ameasuringdeviceisneededforadministration.
The disadvantages of solutions as pharmaceutical Although not a major disadvantage, it must be
products are that: borneinmindthatameasuringdevicewillneedto
be supplied to the patient in order for them to be
* Drugstability is often reduced in solution by able to measure an accurate dose (this will have
solvolysis, hydrolysis or oxidation. The stability costimplications),andinadditionthepatientwill
of the active ingredient needs to be taken into need counselling on the use of the measuring
consideration when formulating a solution. For device.
this reason, it is common for solutions to attract a
shorter expiry date than equivalent solid dosage Theadvantages and disadvantages of solutions as
forms. dosage forms are summarised in Box 6.1.
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Solutions | 103
* WhatisthepHofsolventrequiredfor
Box6.1 Advantages and disadvantages of dissolution?
solutions as dosage forms Answers to many of the above questions will
Advantages Disadvantages require the compounder to perform a solubility calcu-
Drug available immediately Drug stability often lation, as described in Chapter 4.
for absorption reduced in solution Whenpreparingasolution,thesolid(s)willneedto
Flexible dosing Difficult to mask gothroughadissolutionphase.Duringcompounding,
Maybedesignedfor any unpleasant tastes it is worth remembering that dissolution rates gener-
route of administration Bulky, difficult to transport ally increase with:
Noneedtoshakecontainer and prone to container
Facilitates swallowing in breakages * smallerparticle sizes
difficult cases Technical accuracy needed * effective stirring
to measure dose on * lowerviscosities
administration
Measuring device needed * increased temperature.
for administration
Somedrugspoorly soluble Stability
In addition to the solubility of the drug element(s) of
the formulation, other considerations regarding the
General principles of solution physical stability of the preparation will need to be
taken into consideration (e.g. temperature variation,
preparation photosensitivity, etc.), as will the chemical stability
and time period, and the microbiological stability
Historically,arangeofsolutionshavebeendevelopedin and need for a preservative.
order to fulfil a wide variety of pharmaceutical func-
tions. It is therefore common to find solutions classified General method
according to their intended use (e.g. oral internal, topi- The following general method should be used in the
cal, ophthalmic, nasal or parenteral), by the nature of preparation of a solution:
their formulation (e.g. simple or complex), or to be
categorised by a traditional name that relates to the 1 Write out the formula either from the
solvent system used and/or their intended function (e.g. prescription (unofficial) or from an official text
spirits, tinctures, aromatic waters, syrups and elixirs). (official).
Although the precise characteristics of different 2 Calculate the quantities required for each
types of solution may vary, the essential principles ingredient in the formula to produce the
governing their preparation remain similar. The two requiredfinalvolume.Remember,itisnotusual
key characteristics that need to be considered when tocalculateforanoverageofproductinthecase
compounding solutions are solubility and stability. of solutions as it is relatively easy to transfer the
entire final contents of the conical measure.
Solubility Also,asfarasispracticallypossible,theproduct
The following points relating to the solubility of the will be assembled in the final measure, thus
drug element(s) of the formulation need to be taken reducing any transference losses.
into consideration: 3 Complete all sections of the product worksheet
(see Chapter 5, page 70).
* Willthedrug(s) dissolve in the solvent or a 4 Prepare a suitable label (see Chapter 5,
component of the solvent system? page 91).
* Whatquantityofdrugwilldissolve? 5 Weighall solids.
* Howlongwilldissolution take? 6 Identify the soluble solids and calculate the
* Willthedrug(s) remain in solution and for how quantity of vehicle required to fully dissolve the
long? solids. If more than one solid is to be dissolved,
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104 | Pharmaceutical forms and their preparation
they are dissolved one by one, in order of uniformproductandcanbetimesaving.Ifstirring
solubility (i.e. the least soluble first, see Chapter devices are used to assist dissolution (e.g. rod,
4, page 62). In almost all cases, dissolution will magnetic stirrers), remember to remove them
take place in a glass (or occasionally plastic) before adjusting to final volume.
beaker, not a conical measure. Remember that * Itisbesttostir continuously when combining
the solubility of the soluble solids will be ingredients into a solution (either liquid or solid
dependent on the vehicle used. ingredients). By stirring continually during
7 Transfer the appropriate amount of vehicle to a incorporation, high concentration planes within
glass beaker. the fluid body, which might increase the
8 If necessary, transfer the solid to a glass mortar likelihood of incompatibilities, will be avoided.
andusetheglasspestletoreduceparticlesizeto
aid dissolution. Furtherconsiderationsduringthepreparationofa
9 Transfer the solid to the beaker and stir to aid solution:
dissolution. If a mortar and pestle have been * Toaiddissolution, high-viscosity liquid
used to reduce particle size, ensure that the components should be added to those of lower
mortar is rinsed with a little vehicle to ensure viscosity.
completer transfer of the powders. * Completelydissolve salts in a small amount of
10 Whenallthesolid(s)havedissolved,transferthe water prior to the addition of other solvent
solution to the conical measure that will be used elements.
to hold the final solution. * Incomplexsolutions, organic components should
11 Rinse out the beaker in which the solution was be dissolved in alcoholic solvents and water-
madewithaportionofthevehicle and transfer solublecomponentsdissolvedinaqueoussolvents.
the rinsings to the conical measure. * Aqueoussolutionsshould be added to alcoholic
12 Addanyremainingliquid ingredients to the solutions with stirring to maintain the alcohol
conical measure and stir. concentrationashighaspossible–thereversemay
13 Makeuptofinalvolumewithremainingvehicle. result in separation of any dissolved components.
14 Transfer to a suitable container, label and
dispense to the patient. Oral solutions
See Solutions video for a demonstration of the
preparation of a solution. This section describes the different types of pharma-
ceutical solution that are used orally. Although all are
prepared using the same general techniques high-
Key points from the method lightedabove,thereareimportantdifferencesbetween
the different solution types.
* Dissolution will normally take place in a glass
beaker, not a conical measure, for a number of Elixirs
reasons. First, owing to the shape of the conical
measure, any solid added will tend to ‘cake’ at the Anelixir is a liquid oral preparation that usually con-
bottom of the measure and hamper any attempt to tains either potent or unpleasant-tasting drugs. The
stir the solid around with the stirring rod, which formulationisclearandgenerallycontainsahighpro-
aids dissolution. Second, the action of the stirring portionofsugarorothersweeteningagent,includedto
rodmayscratchtheinsideoftheglass,permanently mask offensive or nauseating tastes. Paediatric elixirs
altering the internal volume of the measure. are usually formulated with a fruit syrup as a base
* Duringthedissolutionphase,solutions should be flavouring agent.
stirred gently and uniformly to avoid air Ingeneral,non-aqueoussolvents(alcohol,glycerin
entrapment, which may result in foaming of the or propylene glycol) form a significant proportion of
solution. If available, automatic stirring devices the vehicle used in elixirs, or alternatively solubilising
maybeuseful in assisting the production of a agents are included.
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