Dispensing techniques (compounding and good practice)
Practical aspects of dispensing
The working environment and procedures
Extemporaneous dispensing equipment and its correct use
Manipulative techniques used in dispensing and compounding
Introduction
This chapter deals with some of the practical aspects of dispensing, concentrating on the small-scale manufacture of medicines from basic ingredients. This process is called compounding or extemporaneous dispensing. Additionally, good practice which applies to all aspects of dispensing will be considered.
Nowadays, most medicines are manufactured by the pharmaceutical industry under well-controlled conditions and packaged in suitable containers designed to maintain the stability of the product (e.g. sealed in an inert atmosphere). Extemporaneous dispensing, which cannot be as well-controlled, should only be used when a manufactured product is unavailable. Reasons for unavailability of products may include:
Products no longer on the market or unavailable from the manufacturer
Products requiring an individualized dose, e.g. for paediatric or geriatric patients
Products requiring an individualized formulation for a patient, e.g. the removal of colouring agents
Veterinary products, e.g. formulations for different species.
The pharmacist undertaking extemporaneous dispensing has a responsibility to maintain equipment in working order, to ensure that the formula and dose are safe and appropriate and that all materials are sourced from recognized pharmaceutical manufacturers. There are also requirements concerning calculations, maintaining good records and labelling. Any staff involved in the process should be adequately trained. These requirements should all be incorporated within standard operating procedures (SOPs, see Ch. 11).
In any dispensing process, the end-product will be used or taken by a person or an animal. Therefore, it is important that the medicine produced is of the highest achievable quality. This, in turn, means that the highest standards must be applied during the preparation process.
The working environment and procedures
Organization
The working environment needs to be organized, with well trained, efficient staff. A safe system of working is essential for a dispensary and the development and use of SOPs should be followed. Additionally, health and safety regulations must be applied in the dispensary.
Cleanliness and hygiene
The dispensing bench, the equipment, utensils and the container which is to hold the final product must all be clean. Lack of cleanliness can cause contamination of the preparation with other ingredients. For example, a spatula which has been used to remove an ingredient from one container will adulterate subsequent containers if not washed before being used again. Cleanliness will also minimize microbial contamination.
Dispensing staff should have a high standard of hygiene and hand-washing facilities should be readily available. A clean overall should be worn, hair tied back and, preferably, be covered with a disposable hat/cap and any skin lesions covered with a dressing. Disposable gloves should be worn during preparative work and discarded afterwards. Consideration should be given to the use of masks if volatile substances or fine powders are to be handled.
Documenting procedures and results
Keeping comprehensive records is an essential part of the dispensing process. Records must be kept for a minimum of 2 years (ideally 5 years) and include the formula and any calculations, the ingredients and quantities used, their sources, batch numbers and expiry date. All calculations or weights/volumes should be checked by two people and recorded. Any substances requiring special handling techniques or hazardous substances should be recorded with the precautions taken. The record for a prescribed item should also include the patient and prescription details and date of dispensing. A record must be kept of the personnel involved, including the responsible pharmacist. Any deviations from a SOP should be recorded.
Equipment
Not only is the selection of the correct equipment for the job essential, but the equipment must be used in the correct way and maintained in good order.
Weighing equipment
Weighing equipment can be divided into non-automatic and automatic weighing equipment. Non-automatic weighing equipment requires an operator to place and/or remove the items from the balance pan. Such weighing equipment can be a mechanical beam balance, which has a pan on one end of the beam for weights and a pan on the other end of the beam for the material to be weighed (Fig. 30.1) or it can be an electronic top-pan balance, in which case the substance to be weighed is placed on the pan and an electronic display gives the weight. Automatic weighing equipment is designed to automatically fill a package to the required weight without the intervention of an operator. Such equipment is used in the pharmaceutical industry, and nowadays for extemporaneous dispensing. Whichever type of weighing equipment is used, it must be suitable for its intended use and be sufficiently accurate. In the UK, weighing equipment must be calibrated in metric units and must be marked with maximum and minimum weights that can be weighed.
General rules for the use and maintenance of weighing equipment
The following points are important to ensure accurate weighing:
Balances must be placed on a level surface; most will incorporate a level indicator device to allow adjustment for a non-level surface
Balances’ readings must indicate zero, before use. If zero is not indicated, then incorrect readings, and hence weights, may be obtained
Strong draughts, caused by air conditioning or a breeze, can affect some balances and make a correct reading impossible. Therefore always site a balance in a draught-free area
Always keep the balance pan clean and free from debris
Regular checks with stamped weights should be made to ensure the balance is working correctly
If possible keep a record of when, and by whom, the check was carried out, as well as the result
Never weigh less than the declared minimum weight or more than the maximum weight declared on the balance
Do not weigh ingredients on a piece of paper, as this introduces a potential inaccuracy. The exception is when weighing greasy or semi-solid materials, e.g. white soft paraffin, when a counterbalanced piece of paper should be used
Always read the manufacturer’s instructions before using an electronic balance
Use tweezers to handle weights, if used. Never handle weights, as this will affect their accuracy and risks contamination.
Measuring liquids
Liquid measures
All measures for liquids must comply with current weights and measures regulations and should be stamped accordingly. Traditionally, conical measures (Fig. 30.2) have been used in dispensing.
When using a measure always ensure the following:
The level of liquid is read to the bottom of the meniscus at eye level
The measure is vertical when reading the meniscus. If this is not done, considerable errors in quantities can occur
The measure is thoroughly drained to deliver the correct volume
Always select the smallest measure which will hold the desired volume because this gives the greatest accuracy
If the substance being measured is so viscous that it would be very difficult to drain the measure effectively, then the volume should be measured by difference. This is done by pouring an excess into the measure and then pouring off the liquid until only the excess volume remains.
Measuring small volumes
Graduated pipettes can be used for small volumes from 5 mL down to 0.1 mL. For volumes smaller than this, a dilution should be made. The viscosity of the substance being measured should also be considered.
Correct use of pipettes
Pipettes can be either the ‘drainage’ or ‘blow-out’ variety. A rubber bulb or teat should be used. Never use mouth suction.
A bulb or teat should be placed over the mouth of the pipette
Only a short length of the pipette should be immersed in the liquid
The correct amount of liquid should be drawn up the pipette
The measured liquid is then released into the desired container.
Nowadays, semi-automatic pipettes can be used for dispensing.
Mixing and grinding
Mortar and pestle
The mortar (bowl) and pestle (pounding device) are used to reduce the size of powders, mix powders, mix together powders and liquids and to make emulsions. Two types, each available in a range of sizes, are used.
Glass mortar and pestle
These are generally small. The smooth surface of the glass reduces the friction which can be generated, so they are only suitable for size reduction of friable materials (such as crystals). Glass mortars and pestles are useful for mixing small quantities of fine powders and for the mixing of substances such as dyes which are absorbed by and stain composition or porcelain mortars.
Porcelain or composition mortars and pestles
These mortars have a rough surface. They are ideal for size reduction of solids and for mixing solids and liquids, as in the preparation of suspensions and emulsions.
Size reduction using a mortar and pestle
Selection of the correct type of mortar and pestle is vital for this operation. A flat-bottomed mortar and a pestle with a flat head should be chosen.
Using a mortar and pestle for mixing powders
Adequate mixing will only be achieved if there is sufficient space. Overfilling of the mortar should be avoided. The pestle should be rotated in both right and left directions to ensure thorough mixing. Undue pressure should not be used, as this will cause impaction of the powder on the bottom of the mortar.
Filters
There are occasions when clarification of a liquid is required. Where filtration is required, filter paper or membrane filters should be used. Filter paper and membrane filters come in different grades and selection of the correct grade is determined by the size of the particles to be removed. Filter paper has the disadvantages of introducing fibres into the filtrate and may also absorb significant amounts of active ingredient. This is less likely with membrane filters.
Manipulative techniques
Selection of the correct equipment and using it appropriately is fundamental to good compounding. Several basic manipulative techniques may require practice.
Mixing
The goal of any mixing operation should be to ensure even distribution of all the ingredients has occurred. If a sample is removed from any part of the final preparation, it should be identical to a sample taken from any other part of the container.
Mixing of liquids
Simple stirring or shaking is usually all that is required to mix two or more liquids. The degree of stirring or shaking will be dependent on the viscosities of the liquids.
Mixing solids with liquids
Particle size reduction will either speed up the dissolution process or improve the uniform distribution of the solid throughout the liquid. When a solution is being made, a stirring rod will be adequate. However, a suspension will require a mortar and pestle.
Mixing solids with solids
Where the quantity of material to be mixed is small and the proportions are approximately the same, the materials can be added to an appropriately sized mortar and effectively mixed. Where a small quantity of powder has to be mixed with a large quantity, in order to achieve effective mixing, it must be done in stages:
The ingredient with the smallest bulk is placed in the mortar
A quantity of the second ingredient, approximately equal in volume to the first, is added and carefully mixed, using the pestle
A further quantity of the second ingredient, approximately equal in volume to the mixture in the mortar, is now added
This process, known as ‘doubling-up’, is continued until all the powder has been added (see Ch. 38).
Mixing semi-solids
If all the ingredients are semi-solids or liquids, they can be mixed together by rubbing them down on an ointment slab, using a spatula. If there is a significant difference in the quantities of the ingredients, a ‘doubling-up’ process should be used. An alternative method is the fusion method.
The fusion method
Place the bases in an evaporating basin and gently heat until they have just melted. Excess heat should not be used, as overheating may cause physical or chemical changes in some materials
The basin is then removed from the heat and the contents are stirred continuously, but gently, until the mixture has cooled and set. Stirring at this stage is of vital importance as otherwise the components may segregate on cooling. Rapid stirring should be avoided as it will introduce air bubbles into the mixture.
When using the fusion method, do not be tempted to add any solid active ingredients to the basin before the bases have set. Addition of any further ingredients is best done by rubbing down on an ointment slab. (Further details of methods used in the preparation of ointments can be found in Ch. 36.)
Tared containers
Liquid preparations should, as far as possible, be made up to volume in a measure. There are, however, instances when accurate transfer of the preparation to the final container is difficult, e.g. with some suspensions it can be almost impossible to remove all the insoluble ingredients when pouring from one container to another. Emulsions and viscous preparations can also be difficult to transfer accurately. In these cases, a tared container should be used.
To tare a bottle
A volume of potable water identical to the volume of the product being dispensed is accurately measured. This is then poured into the chosen medicine container and the meniscus marked with the upper edge of a small adhesive label, effectively making the bottle into a single-point measure. The container is then emptied and allowed to drain thoroughly. The preparation is then poured into the container and made up to volume, using the tare mark as the guide. Remove the tare label.
Ingredients
All ingredients must be sourced and obtained from reputable suppliers and be of a quality suitable for the preparation and dispensing of pharmaceutical products. Additionally, ingredients must be suitably stored to preserve stability and integrity. For example, regular checks on expiry dates of stored products should be made and any ingredient outside its expiry date should be discarded. Some ingredients may require special storage conditions and these should be provided. Many pharmaceutical ingredients and products require storage in a refrigerator, which should be fitted with a maximum/minimum thermometer and both maximum and minimum temperatures checked and recorded on a daily basis.
Selection
When dispensing, selection of the correct product is vital. The label on each container must be read carefully and checked to ensure that it contains the required product. There are many examples of drugs and preparations where names may be misread if care is not taken; examples include folic acid and folinic acid, cefuroxime and cefotaxime. (Further examples are given in Ch. 27.)
Variety of forms
Some ingredients of extemporaneously dispensed medicines may occur in a variety of forms or a synonym is used. Coal tar, for example, is available as coal tar solution, strong coal tar solution and coal tar. Some other materials where confusion can occur are listed in Table 30.1. This list is not meant to be comprehensive and only contains common exemplars. To reduce the risk of errors you need to read the container label carefully and have it checked by a second person.
Table 30.1
Some substances which occur in a variety of forms
| Substance/form | Use |
| Light magnesium carbonate | Because of its lightness and diffusible properties, it is used in suspensions |
| Heavy magnesium carbonate | Normally used in bulk or individual powders |
| Light kaolin | Used in suspensions |
| Heavy kaolin | Used in the preparation of kaolin poultice |
| Precipitated sulfur | This has a smaller particle size than sublimed sulfur and is preferred in preparations for external use, e.g. suspensions, creams and ointments |
| Sublimed sulfur | Slightly gritty powder, which does not produce such elegant preparations as precipitated sulfur |
| Yellow soft paraffin | Used as an ointment base |
| White soft paraffin | Bleached yellow soft paraffin, normally used when the other ingredients are not strongly coloured |
Problem-solving in extemporaneous dispensing
For extemporaneous dispensing, it is helpful if a method detailing how to prepare the product is available. Methods for ‘official’ preparations can sometimes be found in reference sources such as the Pharmaceutical Codex. However, on many occasions, no method is available. In such a situation, it may be helpful to consider similar formulas in reference sources. Additionally, the application of simple scientific knowledge, especially of physical properties, is often all that is needed. The following gives an example of how this is done.
Putting theory into practice
Solubility
Always check the solubility of any solid materials. If they are soluble in the main vehicles, then a solution is likely to be produced. If solubility is limited to one liquid, this will assist in achieving uniform dose distribution. Solution will be achieved more quickly if the particle size is small and so size reduction should be considered for any soluble ingredients which are presented in a lumpy or granular form. It is also necessary to add less soluble solids before more soluble solids. If the substance is not soluble, then a suspension will need to be produced. Whether a suspending agent will be required should be considered (see Ch. 34). Where one material is an oil and another aqueous, it is likely that an emulsifying agent will be required to produce an emulsion (see Ch. 35).
Volatile ingredients
If an ingredient is volatile then it should be added near the end of the dispensing process and often directly into the final container. If it is added too early, much may be lost due to evaporation.
Viscosity
The viscosity of a liquid will have a bearing on how it is measured, i.e. is a pipette or measure suitable, or should it be measured by difference, and how will it be incorporated?
Expiry date
All extemporaneously prepared products should be labelled with an expiry date. Ideally, stability studies should be undertaken in order to predict an accurate shelf-life for all products. This is not usually possible for ‘one-off’ preparations and most hospital pharmacies have guidelines based on previous stability studies. If in doubt, use the shortest possible expiry date, e.g. 3 days, and be prepared to produce the medicine in small quantities every 3 days.
Key Points
Extemporaneous dispensing should only be used when manufactured medicines are not available
Accurate dispensing requires clean and methodical work
Comprehensive records of extemporaneous dispensing are required to be kept for at least 2 years
Always use all equipment correctly
Ensure that liquid measures comply with the weights and measures regulations
Always use the bottom of the meniscus when measuring liquids
Viscous liquids should be measured ‘by difference’
Select the smallest measure or pipette for the volume of liquid to be measured
A glass mortar and pestle can be used for size reduction of friable materials and mixing small quantities of fine powder
A porcelain mortar and pestle is used for larger quantities, for mixing solids and liquids, making emulsions and for size reduction
Confusion can arise with different forms of the same material and the use of synonyms
Simple problem-solving techniques can produce a satisfactory method of dispensing a product