– Sumit Goel.
CaO and other oxides.
The medication is not completely prepared unless it is properly packed. The stability of the product is totally dependent on the proper functioning of the package.
Packaging is the art and science of, and the operations involved in preparing articles for transport, storage and use. Similar principles apply to packaging extemporaneously dispensed medications.
Unless otherwise indicated, the official standards for containers apply to articles packaged either by the pharmaceutical manufacturers or the dispensing pharmacist.
A PACKAGE consists of –
* The container in which the product is placed;
* The closure, which seals the container to exclude air, moisture, bacteria, etc. and prevents loss of product. A pharmaceutical container is defined as a device that holds the drug and which is in direct contact with the preparation. The immediate container is described as that which is in direct contact with the drug at all times. The closure is traditionally considered to be a part of the container system.
* The carton or outer cover, constructed from a variety of materials such as cardboard, moulded wood pulp, which gives secondary protection against mechanical and other environmental hazards and also serves as the display of written information.
* The box in which multiples of the product are packed. The box provides primary defence against external hazards and usually incorporates suitable shock absorbing features.
FEATURES OF PACKAGING AND PRESERVATION
The packaging of any homoeopathic product must be economic and must be able to preserve the quality of the medication it contains to ensure complete therapeutic activity against all physical, chemical and biological deterrents during handling, storage and transport.
* The container must be rigid enough to prevent damage to the contents. The containers must be made of materials that would stand the rigors of normal handling. Glass has the disadvantage of being brittle. Advent of plastics has overcome this shortcoming.
* The material of the container must not react with the medication contained in the container either physically or chemically so as to alter the strength, quality or purity of the contents. If interaction is unavoidable, the alteration must not be so great as to bring the substance below pharmacopoeial requirements. The containers must themselves behave in a ‘neutral’ way towards the medication they contain.
* The closure of the container must prevent – Access to moisture in case of globules and alcoholic preparations.
– Loss of moisture from creams and from water containing ointments and preparations.
– Unintentional escape of contents.
– Entry of dirt or other contaminants.
* The container must contribute to the stability of the product against environmental deteriorators. When required, it must give protection from deteriorating wavelengths of light. If the medication is to be maintained in a sterile state, the container should be microbe-proof.
* Medicaments must not be absorbed by the material of the container nor it should diffuse through the walls of the container.
* The containers should be so designed as to facilitate withdrawal of the required dose in a convenient manner as and when required. E.g. attached dropper or a nozzle. The container for eye drops must ensure that the medicament is transferred directly to the eye.
* The container should be capable of proper reclosure, once the container is opened, for further use.
* The cost of the packaging must be reasonable in relation to the cost of the product.
This container prevents the contents from contamination under normal conditions of handling, storage, transport and sale, and also prevents unintentional release of the contents.
This container gives protection from extraneous solids, liquids and vapours under normal conditions of handling, storage and transport.
This container is impervious to air and other gases under normal conditions of handling, storage and transport.
An ideal closure has to seal the container to prevent loss of product and ingress of gases or other substances. Where necessary, the closure should withstand sterilizing conditions and prevent subsequent contamination. If only part of the contents is to be used at a time, it should be easy to remove and should be capable of proper reclosure.
The basic types of closure are folded, push-on, bung and screw cap.
These are usually seen in collapsible tubes as the folded end of the tubes. In commercial practice, when the folds have been formed, they are crimped by corrugated jaws and this prevents unfolding of the seal.
These rely on the resilient distortion of the closure both for pushing the cap over the retaining ring at the rim of the tube and also for maintaining a tight seal between the neck and the rim.
These are conical and can be inserted for about half their length into the neck of the container. Cork usually gives a good seal for general purposes but eventually becomes permanently distorted with consequent loss of reseal properties. Rubber and plastic bung seals may also be used.
The essential features are a cap with thread matching that of the container, and a tough liner behind which is placed a resilient wad. When the cap is screwed down, the liner makes contact with the rim, distortion of the wad maintaining the liner in close contact with the rim. For efficient sealing, the thread on the cap must match that on the container and must be free from moulding imperfections.
MATERIAL OF CONTAINERS AND CLOSURES
The choice of containers or closures for mother preparations, potentized medicines, triturates or powders, external applications and other medications can have a profound effect on the stability. There are a large variety of glasses, plastics that are available.
Stability studies of the containers and closures should be carried out with a special emphasis on the inner walls, migration of ingredients onto / into the container or closure and possibility of two-way moisture penetration through container walls must be studied.
The containers and closures used for pharmaceutical products are constructed from basic materials like glass, plastic, rubber, metal, paper, etc.
Traditionally glass has been the most widely used container for pharmaceutical products to insure inertness, visibility, strength, rigidity, moisture protection, ease of reclosure and economy of packaging.
It is composed chiefly of silicon dioxide with varying amounts of other oxides such as sodium, potassium, calcium, magnesium, aluminium, boron and iron. The basic structural network of glass is formed by the silicon oxide tetrahedron. Boric oxide will enter into this structure, but most of the other oxides do not. The latter are only loosely bound, are present in the network interstices and are relatively free to migrate.
Glass containers must be strong enough to withstand the physical shocks of handling and the pressure differentials that develop during autoclave sterilization cycle. They should also be able to withstand thermal shock and hence glass of a low coefficient of thermal expansion is necessary. It must be transparent to permit inspection of contents.
Preparations that are light sensitive must be protected by placing them in amber glass containers. Light waves, especially those falling within ultra-violet region bring about decomposition of many drug products. Since glass is transparent, it is permeable to these wavelengths and products stored in ordinary glass undergo deteriorative decomposition. Amber colour intercepts ultra-violet radiation and hence prevents against photochemical deterioration. For total light restriction, opaque glass or glass rendered opaque by covering with black paper or by special coating may be employed. Certain elements like carbon and sulphur or iron and manganese maybe deliberately added to produce amber-coloured glass.
* Lime-soda glass
The most common type of glass consists of calcium and sodium oxides besides silica and is referred to as lime-soda glass. The containers of lime-soda glass yield alkalinity to aqueous matter readily, which can adversely affect the quality of contained products.
Approximate composition is 73 Pecent SiO2, 0.5 Pecent Al2O3, 13 Pecent Na2O, 10 Pecent CaO, 0.5 Pecent K2O and 0.3 Pecent MgO.
* Boro-silicate glass
The defects of lime-soda glass can be largely overcome by decreasing the proportion of alkali (CaO, Na2O) and including boric oxide; the latter improves heat resistance and confers great chemical durability. These compositions are called boro-silicate or resistance glasses and are used for chemical glassware, ovenware and containers for alkali-sensitive preparations. Aluminum oxide is usually present and the silica content is often increased, with advantages mentioned earlier.
Approximate composition is 80 Pecent SiO2, 12 Pecent B2O3, 2 Pecent Al2O3, 6 Pecent Na2O + CaO and other oxides.
* Neutral glass
Boro-silicate glasses have two major disadvantages – they are expensive and difficult to melt and mould. In consequence, manufacturers have produced grades of glass (described as neutral) between boro-silicate and lime-soda glass in composition but with suitable characteristics for pharmaceutical purposes. They are softer and more easily manipulated than boro-silicate glass but have good resistance to autoclaving, weathering and solutions of pH upto about 8.
Approximate composition is 72-75 Pecent SiO2 , 7-10 Pecent B2O3, 4-6 Pecent Al2O3, 6-8 Pecent Na2O,
0.5-2 Pecent K2O and 2-4 Pecent BaO.
Plastics are synthetic polymers of high molecular weight and have become popular in packaging and dispensing of medications.
They are either thermosetting type or thermoplastic type. The thermosetting types are usually hard and brittle at room temperature, although on heating, become flexible. They are mainly used for construction of closures. Thermoplastic type of plastics are characterized by the fact that on heating, they soften to viscous fluids while on cooling, harden once again.
For packaging of pharmaceutical products into plastic containers, the same must be adequately tested. Compared with glass, plastics offer the advantage of lightness, resistance to mechanical hazards and low cost. Against these advantages must be set the problems of permeability and toxicity, neither of which arise with glass, and of disposal. In selecting plastic containers, it is necessary, to check that –
i. Toxic substances are not leached from the plastic into the product;
ii. Medication is not lost by absorption or permeation;
iii. No other interactions can occur between product and container.
Large number of plastic containers are now employed by the pharmaceuticals as well as the dispensing pharmacist for dispensing globules, tablets, ointments, etc.
Metals are not popularly used as packaging material, because of their reactiveness, high cost and considerable weight. Aluminium is more popularly used. Aluminium containers are produced by extrusion and are light and cheaper. They are used for preparing collapsible tubes as well as for strip and blister packs.
Rubber may be natural or synthetic. Rubber is used exclusively as a closure and wad material.
So far as paper is concerned as a packing material, it may be used to dispense unit powder doses. They are otherwise used in the form of cartons for carrying bulk medicines. Powders are wrapped in white glazed paper, cut to a suitable size, depending upon the bulk of the powder.
MODERN PACKAGE FORMS
* Strip or Blister packs
Unit dose forms can be individually protected by enclosure in strip or blister packs. In the former, the units are hermetically sealed within strips of aluminium foil and / or plastic films. In the latter, one of the films enclosing the units is formed into blisters. The contents are removed from strip packs by tearing or cutting to separate one pocket and extracting the dose form by the same method. With blister packs, the usual method of extraction is to press on the blister and force the contents through the backing strip.
An ideal foil or film for these packs should be heat stable, impermeable to moisture, water vapour, air or odours, strong enough for medicine handling, reasonably easy for patient to tear and most importantly it should be able to preserve the quality of the homoeopathic medicine.
Aluminium foil is used for strip packing and as a backing film in blister packs. Polyvinyl chloride (P.V.C.) has excellent clarity and is easily formed into blisters. Its permeability to oxygen is low, but it is highly permeable to moisture.
* Collapsible Metal or Plastic tubes
These are used for semi-solid preparations like ointments.
The narrow orifice prevents serious contamination of the unused part of the contents. When part of the preparation is expelled, it is not replaced, as in other containers, by an equivalent volume of air; consequently, microbial contamination and degradation of contents is reduced.
Most collapsible tubes are made from aluminium, although tin, lead, tin-coated lead and plastics are also used.
HAZARDS ENCOUNTERED BY THE PACKAGE The package passes through a number of stages and during this time, the package undergoes transport, including manual (and mechanical) handling by road, rail, sea or air; storage and use. The main hazards encountered by the package and its contents are –
Damage due to shock is normally caused due to rough handling or carelessness during transport.
Fragile items may be broken or crushed by compression. This is minimized by protection with a rigid outer package.
* Vibration Considerable vibration may occur during transport, especially with exported items.
It is only in this form (globules medicated with the medicinal fluid) that homoeopathic medicines can be sent to the most distant parts without any alteration of their powers, which is impossible to be done in their fluid form; for in that case the medicinal fluid, which has already been sufficiently potentized during the preparation, receives an enormous number of additional succussions during the transport and they are so highly potentized during a long journey, that on their arrival they are scarcely fit for use, at least not for susceptible patients on account of their excessive strength.
* Temperature Extreme conditions may cause deterioration. Low temperatures may lead to freezing. High temperatures increase diffusion coefficients, accelerating the entry of water vapor into hygroscopic products and loss of volatile component.
Deterioration may be due to photochemical reaction, particularly affected by the ultra-violet band of the spectrum.
Packaging materials, particularly those of a cellulosic nature, are liable to attack by various living organisms, from bacteria to rodents. Moulds may grow on paper, in the presence of moisture. The outside of container may become dirty on transport or storage, but the contents may not be affected. Of greater importance, is that the product may become contaminated by the odour of packaging, printing inks or of foreign materials that may permeate through the package.
PACKAGING AT THE DISPENSING COUNTER
In dispensing a prescription, the dispenser selects a container from amongst various shapes, sizes, mouth openings, colours and composition. Selection is primarily based upon nature and quantity of the medications to be dispensed and method of its use.
– Containers used for keeping one medicine should never be used for any other medicine, nor for the same medicine in any other potency.
– Preferably, two containers containing different potencies or medicines should not be opened in close proximity to each other.
– Potentized medicines should be kept separately from crude drugs
– Bottles should preferably not be filled entirely, as the medicines may come in contact with the corks.
– Separate arrangements should be kept for potentized medicines and other odourous and non-odourous evaporating substances. Avoid dust, odour, smoke, damp, heat and direct sunlight that might affect the purity of potentized medicines.
* Globules, Tablets, Cones: colourless / opaque / amber coloured glass or plastic vials or containers. Unit doses in form of blister / strip packing.
* Powder: paper packets for unit dose form.
* Tinctures, Liquid potencies, Syrups, etc.: narrow-mouthed screw-capped colourless / amber coloured glass bottle with / without dropper.
* Ointments, other semi-solid preparations: wide-mouth, screw-capped, plain glass / plastic OR collapsible tube of metal /plastic with screw cap with impermeable liner or very close fitting slip on lid.
As to the dispensing of the ointment, it should never be dispensed in a wooden box.
Ointment jars – Ointment jars are filled mechanically to somewhat less than capacity to minimize contact between the ointment and the cap or cap-liner.
Ointment tubes – Ointment tubes have obvious advantage over jars; the use of fingers is minimized, as is dust and air contact and light exposure.
* Eye drops: Eye drops are commonly dispensed in bottles with a screw cap fitted with a rubber teat and glass dropper for application of the drops or in plastic containers with a narrow nozzle from which drops can be exuded.
Guidelines for Preservation of Mother Tinctures, as per HPI
* Acidum hydrofluoricum – Hydrofluoric acid and all its preparations below 4X potency should be kept in well-closed bottles, the interior of which is coated with paraffin or well-closed containers of paraffin, lead or wax.
* Acidum nitricum – Preparations upto 3X are to be stored in well-closed containers with glass stopper.
* Acidum nitromuriaticum – All preparations of this acid should be kept in glass stoppered vials and in a cool dark place.
* Acidum picricum – Keep in well-closed container in a cool place remote from fire.
* Acidum sulphuricum – Potencies prepared in purified water should be freshly prepared and all preparations of this acid should be kept in ground stoppered vials.
* Acidum tannicum – Potencies upto 3X to be stored in amber colored containers.
* Adrenocorticotrophin – All potencies below 6X should be kept in a well-closed container protected from light and stored at a temperature not exceeding 25oC. Under these conditions it may be expected to retain their potency for about two years.
* Alumina – Keep in tight container and store in cool place.
* Ammonium carbonicum – Preserve in well-closed light resistant containers preferably and at temperature not above 30oC.
* Amyl nitrosum – Preserve in well-closed container, protected from light and in a cool place away from fire.
* Antimonium sulphuratum aureum – Store in amber colored well-closed container.
* Argentum nitricum – Argentum nitricum and its preparations upto 6X potency are to kept in well closed container protected from light.
* Aviaire – Preparations below 6X should be stored at a temperature about 5o but should not be allowed to freeze.
* Borax – Should be kept in a well-closed container.
* Bromium – Bromium and all its preparations below 4X potency should be kept in glass stoppered bottles, well closed in a cool place. Handle with great care as it causes severe burns and blisters when brought into contact with skin. Solutions and potencies upto 5X should be stored in a dry cool place protected from light and preferably should be prepared fresh for use.
* Calcarea carbonicum – Preserve in a well-closed container.
* Calcarea phosphoricum – Preserve in a well-closed container.
* Camphora – Tincture and potencies are kept in well-closed container in a cool place.
* Carbo vegetabilis – Preserve in a well-closed container.
* Diphtherinum – Preparations below 6X should be stored at a temperature about 5o, but should not be allowed to freeze.
* Ferrum metallicum – Preserve in a well tightly closed containers.
* Glonoinum – Keep in a well-closed container protected from light and in a cool place.
* Hepar sulphuricum – Preserve in well-closed glass stoppered bottles and protected from light.
* Iodium – Preserve Iodine in an amber glass stoppered bottle or in earthenware container with a well waxed bung.
* Kali bichromicum – Below 3X, fresh preparation of this salt should be used and should be discarded if there is decolouration, sedimentation or visible particles.
* Kali carbonicum – Keep in completely filled and well-closed container.
* Lachesis – It should be stored in glycerin.
* Magnesium carbonicum – Preserve in well-closed container.
* Magnesium muriaticum – Preserve in well-closed container in a dry place.
* Medorrhinum – Preparations below 6X to be stored at a temperature about 5o and are not to be allowed to freeze.
* Mercurius cyanatus – Preparations below 3X to be stored in amber colored containers.
* Mercurius iodatus flavus – Preserve in tightly closed light resistant containers.
* Mercurius iodatus ruber – Preserve in tightly closed light resistant containers.
* Mercurius solubilis – Keep in well-stoppered bottles protected from light.
* Morphinum – Preparations below 6X should preferably be kept in neutral glass containers protected from light.
* Natrum chloratum – Keep out of contact with organic matter and other oxidisable substances.
* Natrum muriaticum – Preserve in well-closed container.
* Natrum phosphoricum – Preserve in well-closed container.
* Natrum sulphuricum – Preserve in tight container and keep in a cool place.
* Petroleum – Preserve in well-stoppered bottles.
* Phosphorus – Keep under water in strong well-closed containers in a cool place and protected from light. Handle carefully with forceps.
* Radium bromatum – Glass bottles or sealed tubes enclosed in lead sheet.
* Shigella dysenteriae – Preparations below 6X to be kept at about 5o and not allowed to freeze.
* Sparteinum sulphuricum – Preparations below 6X to be kept in neutral (alkali free) containers protected from light.
* Syphilinum – Preparations below 6X to be stored at a temperature about 5o.
* Tuberculinum – Preparations below 6X to be stored at a temperature about 5o and not allowed to freeze.
* Uranium Nitricum – All preparations below 3X to be freshly made
* Zincum Iodatum – Preserve in a well-closed container protected from light
* Zincum Oxydatum – Preparations below 3X to be kept in well-closed container
* Zincum Phosphatum – All preparation below 6X to be kept in well-closed container protected from light
* Discuss preservation and packaging of homoeopathic medicines.