THE TECHNOLOGY OF SOLID DOSAGE FORMS (TABLETS, SOFT TABLETS, PILLS, CRYSTALS AND GRANULES).
TECHNOLOGY FEATURES.
THE PRINCIPLES OF QUALITY CONTROL AND REGISTRATION TO DISPENSE
SOLID DOSE FORMS
Solid dose forms are illustrated in Figure 1. They are shown in 14 g glass vials.
In allopathic medicine, tablets and capsules are made in different forms to control the speed at which the active ingredient is delivered.
In homeopathy we are not faced with a necessity for sustained release or enteric coated preparations so the choice of carrier is governed by convenience rather than therapeutic efficiency. There is presently no standard for solid dose forms in the BHomP, so size and ingredients are likely to vary from one manufacturer to another.
Fig. 1 Solid dose forms (from left: tablets, soft tablets, pills, crystals and granules)
Crystals. Solid preparations composed of sucrose, resembling granulated sugar and intended for oral or sublingual use. Coated (‘medicated’) with a 95% alcohol preparation of one or more homeopathic potencies and usually administered by measuring approximately 10–20 crystals per dose.
Usually, dispensed in clear, or amber glass vials with screw cap, or in a single dose sachet, similar to homeopathic powders.
Granules. These are also called ‘non-pareils’, ‘globules’ and ‘globuli’. Granules made from cane sugar of the highest quality. Very small solid spherical preparations composed of sucrose, and intended for oral or sublingual use. Coated with a 95% alcohol preparation of one or more homeopathic potencies and usually administered by measuring approximately 10–20 granules per dose.
Usually dispensed in clear or amber glass vials with screw cap or in a single dose sachet, similar to homeopathic powders. Size and composition vary by manufacturer, but sucrose granules of approximately 0.8–1.0 mm diameter have been common in the UK although a much finer product is now also used (see Fig. 1).
As required in homeopathic pharmacies granules saturated with a certain amount of liquid preparations (essential oils, tinctures, solutions, etc.). After this, granules are dried, each has a weight of 0,032-0,033 g. If the number of granules is not signed in the recipe, they dispensed of 10.0 g.
The preparing of the granules is that way:
The vessel is charged with granules at the rate of 1 kg of granules to 10.0 g corresponding of dilution, added 10.0 g of 60% ethanol, tightly sealed and shaken for 10 minutes by hand or 3-4 minutes by use of mechanization.
The granules are dried in the air, and then pouring them into the appropriate containers.
Do not saturate the granules medicines made from volatile, odorous substances, as well as of all acids in concentrations below the third centesimal dilutions.
For example, Aurum muriaticum 6 gran.
8 granules 3-4 times a day
Pills. These are also called ‘pillules’, ‘granules’ or ‘globules’ in some non-English-speaking countries. Pills are solid spherical dose unit preparations composed of sucrose, lactose or a compound of the two, intended for oral or sublingual use. Coated (‘medicated’) with a 95% alcohol preparation of one or more homeopathic potencies. Pillules are often found to be non-uniform in their size and shape, particularly if the manufacturers have obtained their stocks from food manufacturers rather than from specialist producers. In many cases the pills are built up by adding successive aliquots of liquid sucrose in a revolving drum, and it is rather difficult to control the dimensions of the finished product using this method. Continental European and South American suppliers offer pillules in different sizes and their product tends to be more uniform (weighing on average 0.0435 g) but naturally more expensive. Pillules of approximately 3 – 4 mm diameter are most common in the UK.
Dispensed in clear or amber glass vials with screw cap.
Powders – individual. Made from lactose impregnated with liquid potency, individual powders are especially useful for combined medicated and placebo treatments or where one remedy must follow another in sequence. The powders can be individually numbered in the correct sequence and the patient instructed to take the powders in order. The powders, wrapped and usually packed in multiples of 10, are generally medicated from outside the powder paper, by dropping liquid potency on the long edge of the bundle. The alcoholic solution passes through the powder paper to medicate the lactose powder inside. The powders dry by evaporation of the alcohol. It is important to use a liquid potency made up in a high concentration of alcohol (usually 90%) to facilitate the medication process. Some authorities recommend strengths as high as 96% alcohol. If a low concentration is used some of the lactose dissolves in the water content of the vehicle, giving a damp mass that clumps together.
A solid preparation composed of lactose and intended for oral (directly or dissolved in water) or sublingual use. Approximately 100 mg of powder is coated with a 95% alcohol preparation of one or more homeopathic potencies and enclosed in a paper sachet to form a single dose unit. Individual powders are shown in Figure 2.
Fig. 2. Powders
For example, Calcarea iodata 3 trit.
At the tip of a coffee spoon 3-4 times a day
The trituration of this recipe has prepared according to the 1st method and dispensed as undivided powder. Because the amount of powder is not designated, it has dispensed 10.0 g.
Powder – bulk. Bulk powders have a pure lactose base and are impregnated with liquid potency. Their use has largely fallen out of currency.
Tablets. A solid dose unit preparation, typically white and biconvex, about the same in appearance as a 75 mg dispersible aspirin tablet, and composed of lactose or a compound of lactose/sucrose intended for oral or sublingual use. Usually prepared by compression of a uniform volume of the excipients and then coated with a 95% alcohol preparation of one or more homeopathic potencies. An alternative method of preparation exists in large scale manufacture whereby homeopathic granules are medicated and then compressed to form the tablet in a method similar to allopathic manufacture. Size and composition vary by manufacturer, but lactose tablets of approximately 100 mg weight are most common in the UK. Dispensed in clear or amber glass vials with screw cap.
Soft tablet. A solid dosage form prepared by loose compression of lactose, intended to dissolve readily when administered by the oral or sublingual use. Coated with a 95% alcohol preparation of one or more homeopathic potencies. Dispensed in clear or amber glass vials with screw cap.
Trituration tablet. A solid dose form containing largely insoluble remedies (e.g. Sulphir, Graphites at low potencies) and compressed directly with excipients into a tablet. Few examples of trituration tablets exist but historically they were used widely.
The medicating process for solid dose forms
On a large scale, blank lactose tablets, granules or sucrose pills can be surface inoculated by spraying on the liquid remedy in alcoholic tincture or as a syrup in a revolving pan, rather like the old method of sugar coating. The exact amount of remedy to be applied to ensure an even covering is determined using dyes.
In smaller scale, production the solid dose forms are placed in glass vials and medicated by placing drops of high alcohol medicating potency on the surface, depending on the amount of solid dose form being medicated. This process is shown in Figure 3.
Fig. 3. Medicatin gtablets in a 14 g vial
Two drops of medicating potency (0.2 ml) to about 10 g of dose form is normally used, giving a final remedy content of between 1 and 2% of the raw material. In place of the traditional ‘cork’ method, a capillary dropper can be used. As with the medication of individual powders, it is vital that a high concentration of medicating potency (sometimes called a ‘strong spirit’ or just ‘ss’) is used in this process, as otherwise the tablets can aggregate. The container is agitated in a manner similar to succussion to disperse the remedy throughout the dose form.
For example, the most frequently asked question about this process must surely be: ‘How can you ensure all the tablets receive medicament?’ To illustrate this point is invited to take a bottle of unmedicated tablets and introduce a couple of drops of any alcohol-based perfume. If the tablets are shaken and then turned out on a clean surface, it will be found that every one of the tablets will smell of the perfume. Similarly, when the high concentration alcoholic liquid potency is applied to blank lactose tablets, the vapour is carried throughout the container and this can be checked using an alcohol meter. It is not necessary for every tablet to be coated to the same uniform extent.
For example, years of clinical observation have shown that this medicating technique does produce remedies that are active. Thus, providing we have chosen the right remedy and potency, the amount (within limits, of course) is not important. The frequency of administration is the most important factor in homeopathy, not the size of individual doses.
In acute or first aid situations the remedy is given far more frequently – up to every 10–15 minutes in some cases – whereas in chronic conditions frequencies of once or twice a day (or even once a month) are more appropriate.
By convention it is generally stated that an adult dose should comprise two tablets or pillules and the dose for a child under 12 years should be one tablet or pillule.
Some examples of prescriptions for tablets or pillules are shown in Figure 4.7.
Tablets and pillules.
Prescription 1 is for a 14 g vial of Arnica 6c pills (i.e. a 1:100 serial dilution carried out six times). The dose is one tablet twice daily.
! Note that the letter ‘c’ denoting a centesimal potency is not included, but is implied.
Prescription 2 calls for the remedy Belladonna 30c. No dose form is indicated, but from the quantity ordered we know it must be tablets or pillules. You might consult the prescriber or patient as to his or her preference. The dose here is stated as two, taken three times daily; a dose of one would be equally effective.
Prescription 3 is for a 7 g vial of Sulphur 6x (i.e. a 1:10 dilution six times) in tablet form. The dose is one tablet twice daily.
Prescription 4 is a little more complicated. Here the prescriber has ordered 200 tablets (equivalent to a 25 g vial) of Arnica 10M potency (a 1:100 dilution carried out serially 10000 times) together with 50 tablets of Belladonna 6x potency (a 1:10 dilution six times). In addition the dose of the first remedy is one tablet four times a day and of the second two tablets twice a day.
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Tablets/granules |
Powders |
Mixed powders |
Liquids |
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Prescription 1 Arn 6 pills Mitte 14 g Sig: 1 b.d. |
Prescription 6 H AGE 200 powders Mitte 10 One 4 hrly |
Prescription 7 Arnica 30 1–10 SL 11–16 Belladonna 30c 17–26 SL 27–36 Take in order as directed |
Prescription 9 Crataegus 6x LP 5 drops ex aq om 30 ml |
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Prescription 2 Bell 30c Mitte 50 Sig: 2 t.i.d. |
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Prescription 8 Arnica 30 1–6 7 g SL tablet 1 twice daily |
Prescription 10 Thuja MT Apply 2 drops daily 10 ml |
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Prescription 3 Sulph 6x tabs Mitte 7 g Sig: 1 b.d. |
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Prescription 4 Arn 10M – 200 tabs 1 q.i.d. Bell 6x – 50 tabs 2 b.d. |
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Prescription 5 Cham 6c grans 1 × OP One dose ac for teething |
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Fig. 4. Some examples of prescriptions for tablets or pillules
This example serves to highlight the sort of gross inconsistencies that can be identified occasionally. High potencies such as 10M are usually given in short courses of treatment – one to three doses are not uncommon. A 2-month course would be highly unusual and warrant further investigation. The size of dose should be standardised at either one or two tablets.
Granules, crystals and powders. In comparison with tablets, doses of granules, crystals and powder sound imprecise, but are actually quite reproducible. The cap of a 7 g vial provides a useful means of transferring a suitable amount of medicament. The patient should be instructed to just cover the cap liner by gently tapping out the medicated product until the cap liner is just obscured. The amount thus obtained constitutes a dose. When the remedy is packed in containers other than 7 g vials, another measure is provided by using a salt spoon, filled and levelled off with a knife or other suitable implement. Traditionally homeopaths used the small depression on the side of the wrist formed by crooking the thumb and first finger as a measure. This has been called the ‘anatomical snuff box’.
Prescription 5 shows how granules are ordered. It is for Chamomilla 6c granules, one original pack, with one dose twice daily before food for teething. The original pack may be a 7 g glass vial, available in the UK from two or three small suppliers, or the larger glass and plastic containers produced by the major manufacturers.
Occasionally one sees prescriptions giving ‘five granules’ as a dose. This is not meant to be taken literally – the patient is not expected to count out five tiny granules! It should be taken as the equivalent of a ‘small pinch’. Again, remember we are seeking the smallest amount of remedy that will ‘turn the key in the lock’. Nothing is to be gained from taking larger amounts.
Prescription 6 shows the position of the helpful letter ‘H’ when it is used to signify a homeopathic prescription, with a dose of one powder every 4 hours. Individual powders provide a useful means of controlling single doses. The remedy here is the complex AGE, a mixture of three remedies required as a set of 10 powders in the 200c potency. Unfortunately, the ingredients making up AGE are not consistent throughout the homeopathic community; sometimes the ‘A’ stands for Aconite and sometimes Arsen alb, so it is advisable to check exactly what is required. Other combinations to look out for are: SSC (Silica, Sulphur and Carbo veg) and CGP (Carbo veg, Gelsemium and Phosphorus). Powders are particularly useful where complicated dose regimens are involved. The technique here is to use sets of numbered powders.
Consider, for instance, the following instructions:
‘10 Arnica 30c powders. Take one twice daily. When finished, wait 3 days, then take 10 Belladonna 30c powders. Wait a further 5 days and return to prescriber’.
An elderly person might find these instructions difficult to follow. To make things easier for them, we can assemble a set of 36 powders, physically numbered in sequence in the top corner. The first 10 powders would be Arnica 30c, the next six placebo (plain unmedicated lactose), the next 10 Belladonna 30c and the final 10 placebo again. The patient could then be instructed to take the powders twice daily in sequence until the course is complete and then return to the prescriber. These numbered sets of powders can be ordered from homeopathic suppliers.
If dispensing extemporaneously, care must be taken to ensure the medicated powders are perfectly dry before combining them into the set. A similar use of placebo is made when only one or two medicated powders are indicated (often these are of a very high potency like 10M). To satisfy the expectations of the patient, the course of treatment may be extended by several days with the addition of plain lactose powders.
Prescription 7 shows how numbered powders might be prescribed.
! Note that the prescription may not even mention the word ‘powders’ so unless you appreciate what is required, interpretation is rather difficult to say the least!
Commonly, the abbreviation SL standing for Sacc lach, or milk sugar, is used to denote placebo in any dose form, thus obviating the necessity of writing the dreaded word on the prescription. Another commonly used pseudonym for placebo is 110/P. Occasionally the prescriber may issue a prescription containing different potencies of the same remedy with the aim of treating the physical symptoms first, and then a few days later the mental symptoms, filling the intervening days with placebo.
Prescription 8. shows another variation, with the inclusion of 7 g tablets. Here the prescriber requires six powders of Arnica 30c and 7 g of unmedicated placebo tablets, the patient being instructed to take one powder twice a day until the powders are finished, following on with one tablet twice daily. Placebo tablets may be prescribed alone, in which case they appear on the form written just as SL tablets.
DISPENSING A SOLID DOSE FORMS
A container, preferably glass, should be filled with blank carrier (tablets, pills, etc.) and, for a 7 g vial, two drops of strong spirit liquid potency introduced on the top with a dropper. The bottle is then capped and agitated with a similar action to that used for succussing liquid potencies for between 20 and 30 ‘strikes’.
With a 14 g vial three drops of liquid potency are used;
with a 25 g vial four drops are sufficient.
With larger quantities of tablets and pills and for granules, crystals and powder it is usual to introduce a second oversize container in which to medicate. Thus 7 g of granules will be tipped into a 50 g clean glass bottle, shaken as above until medicated, and then transferred back to the original container. The number of drops given for medicating tablets and pills can be reduced by one drop for granules, crystals and ‘bulk’ powder.
Whenever possible the container used for solid dose forms should be glass, ideally amber to minimise discoloration of product owing to light. For short-term courses of treatment, clear glass or plastic is acceptable.
Larger quantities of remedies (i.e. above 25 g, equivalent to 250 tablets) require amber screw cap bottles. Individual powders are made by bundling together the required number of wrapped blank lactose powders (usually in multiples of three, 10 or 12) and then placing a drop of strong spirit liquid potency on the outside edge of each powder. The medicament passes through the paper and can then be allowed to dry off. Powders are packed in a powder envelope or box.
Granules are kept at a temperature of from 10 to 25 ° C in dry place that is protected from light. Shelf life – 2 years.
The quality control of solid dosage forms:
Powder:
– Organoleptic properties
– Flowability
– Homogeneity and sizes of parts
– Equitability
– Capillary tube fluorimetric assay
– Mass deflection
Granules:
– Organoleptic properties
– The quantity of adhered granules
– Time of decay
– Loss in mass by drying
– Mass deflection
– Capillary tube fluorimetric assay
– Figure Diagrammatic summary of the manufacturing process
