TYPE GENERAL DESCRIPTION
I Highly resistant borosilicate glass II Treated soda lime glass III Soda lime glass
NP General purpose soda lime glass
Chap03.indd 82
may lose their color or physical integrity. A host of pharmaceutical adjuncts, especially those used in tablet formulations, as diluents, binders, and disintegrating agents, are affected by moisture. Most of these adjuncts are carbohydrates, starches, and natural or synthetic gums, and because of their hygroscopicity, they hold mois- ture and may even serve as nutrient media for the growth of microorganisms. Many of the tab- let-disintegrating agents act by swelling, and if they are exposed to high moisture vapor during storage, they can cause tablet deterioration. Many medicinal agents, including aspirin and nitroglycerin, are adversely affected by moisture and require special protection. Sublingual nitro- glycerin tablets must be dispensed in their original glass container.
Specially developed high-barrier packaging can provide added protection to pharmaceutical products against the effects of humidity. Such packaging meets the drug stability requirements adopted by the International Committee on Har- monization, which call for testing of packaged products for a minimum for 12 months at 25°C (77°F) at 60% relative humidity (18). Many cap- sule and other products are liable to deteriorate in humidity unless protected by high-barrier packaging. Desiccant protectants, such as silica gel in small packets, are commonly included in solid-form packaging as added protection against the effects of moisture vapor.
Drug substances that are subject to oxidative degradation may undergo a greater degree of degradation when packaged in plastic than in glass. In glass, the container’s void space is confi ned and presents only a limited amount of oxygen to the drug contents, whereas a drug packaged in a gas-permeable plastic container may be constantly exposed to oxygen because of the replenished air supply entering through the container. Liquid pharmaceuticals packaged in permeable plastic may lose drug molecules or solvent to the container, altering the concentra- tion of the drug in the product and affecting its potency. An example of solvent loss involves large volume parenterals that are packaged in one liter plastic bags that are packaged with an “overwrap” that is removed to yield the con- tainer of fl uid that is actually used. The inside bag may feel slightly damp due to the loss of
fl uid from the primary container that is
entrapped between the primary container and the overwrap.
example, the addition of methyl groups to every other carbon atom in the polymer chains of poly- ethylene will give polypropylene, a material that can be autoclaved, whereas polyethylene cannot. If a chlorine atom is added to every other carbon in the polyethylene polymer, polyvinyl chloride (PVC) is produced. This material is rigid and has good clarity, making it particularly useful in the blister packaging of tablets and capsules. However, it has a signifi cant drawback for packaging medical devices (e.g., syringes): it is unsuitable for gamma sterilization, a method that is being used increas- ingly. The placement of other functional groups on the main chain of polyethylene or added to other types of polymers can give a variety of alterations to the fi nal plastic material. Among the newer plastics are polyethylene terephthalate (PET), amorphous polyethylene terephthalate glycol (APET), and polyethylene terephthalate glycol (PETG). Both APET and PETG have excellent transparency and luster and can be sterilized with
gamma radiation (17).
Among the problems encountered in the use of plastics in packaging are (a) permeability of the containers to atmospheric oxygen and to moisture vapor, (b) leaching of the constituents of the container to the internal contents, (c) absorption of drugs from the contents to the container, (d) transmission of light through the container, and (e) alteration of the container upon storage. Agents frequently added to alter the properties of plastic include plasticizers, sta- bilizers, antioxidants, antistatic agents, antifungal agents, colorants, and others.
Permeability is considered a process of solu- tion and diffusion, with the penetrant dissolving in the plastic on one side and diffusing through to the other side. Permeability should not be confused with porosity, in which minute holes or cracks in the plastic allow gas or moisture vapor to move through directly. The permeability of a plastic is a function of several factors, including the nature of the polymer itself; the amounts and types of plasticizers, fi llers, lubricants, pigments and other additives; pressure; and temperature. Generally, increases in temperature, pressure, and the use of additives tend to increase the per- meability of the plastic. Glass containers are less permeable than plastic containers.
The movement of moisture vapor or gas, espe- cially oxygen, through a pharmaceutical container can pose a threat to the stability of the product. In the presence of moisture, solid dosage forms
Chap03.indd 83
solute may diffuse into the container and be bound within the plastic. The sorption of an active pharmacologic agent from a pharmaceutical solution would reduce its effective concentration and render the product’s potency unreliable. The sorption of pharmaceutical excipients such as colorants, preservatives, or stabilizers would likewise alter the quality of the product. Meth- ylparaben may be sorbed to some types of plastics, resulting in a decrease in the available concentration of the preservative; this may be refl ected in a lowering of its preservative effec- tiveness.
Deformations, softening, hardening, and other physical changes in plastic containers can be caused by the action of the container’s contents or external factors, including changes in tempera- ture and the physical stress placed upon the con- tainer in handling and shipping.
It is always good practice to dispense medica- tion to patients in the same type and quality of container as that used by the manufacturer. In some instances, the original container may be used to dispense the medication.