The United States Pharmacopeia

Pharmaceutical Container Testing

Pharmaceutical containers constructed of materials such as plastic and glass must be qualified and meet USP <661> Containers and <671> Containers-Permeation standards. For example, if the container is intended to provide protection from light (light resistant), it must meet requirements for light transmission. Additionally the containers must meet the requirements for physicochemical tests to determine physical and chemical properties. The following tests are routinely offered.

ANALYSES USP <671> Light Transmission USP <661> Polyethylene Containers USP <671> Single-Unit Container

USP monographs outline many of the requirements for pharmaceuticals, and responsible manufacturers of nutritional supplements wanting to provide a quality product have adapted their processes to meet those guidelines. In addition to its monographs, the USP recently launched a pilot program that will form the basis for a nationwide effort to assess the quality of dietary supplement ingredients and their packaging.

For those manufacturers that supply closures and containers to the pharmaceutical industry, USP 24 <661> and USP 24 <671> define the packaging properties that will maintain the highest level of product quality. The dietary supplement industry has adopted those same regulations. Containers and closures used to package dietary supplements typically include HDPE, PET, unit dose blisters, pouches and blister cards. Because the ingredients intended for these packages can be sensitive to moisture, light, oxygen and heat it is vital that the packaging used is able to prevent disintegration of the product.

Tests performed under USP 24 <671> are used to determine the moisture permeability of containers utilized for prescription drugs. These tests are completed on packages intended for use for dispensing dry prescription drugs in oral dosage. The testing is used to gauge the moisture permeability for multiple unit containers that will be used for capsules and tablets. Because a wide variety of the ingredients used in dietary supplements degrade under moist conditions, it is extremely important that the closures and containers used resist moisture and humidity.

Testing for <671> are conducted on sealed containers and on containers that have been opened and then resealed. The testing consists of a desiccant of set quantity 4-8 mesh, anhydrous calcium chloride being first dried at 110 degrees for one hour then cooled in a desiccator. Then 12 containers of uniform size are selected and opened and closed 30 times each. Closures are applied to the torque specified in the USP monograph. Desiccant is then added to 10 of the packages labeled test containers. These are then filled to within 13mm of the opening on containers larger than 20ml and to two-thirds full on containers smaller than 20ml. The closures are then applied to the torque specified in the monograph.

Tests performed under USP 24 <661 — Polyethylene> characterize high density and low density polyethylene containers that are interchangeably suitable for packaging dry oral dosage forms not meant for constitution into solution. This includes analysis of the container's resistance to light and a determination of heavy metals and extractables.

The following physical tests are performed in accordance to USP 24 <661>:

• Multiple internal reflectance. This test is performed to ensure that the material of the container falls within the range of HDPE or LDPE as specified in the test.
• Thermal analysis. This standard determines endotherms and exotherms temperatures. These temperatures should fall within the ranges specified by the standard.
• Light transmission. These tests are intended to provide protection from light as specified by the standard. Water vapor permeation. These tests are intended to provide protection from moisture permeation as specified by the standard. Water vapor permeation tests are performed using aluminum foil for sealing the open end of the bottle if it is used with a closure.
• Heavy metals. Under these tests, containers must meet the requirements for heavy metals under Physicochemical Tests — Plastics.
• Nonvolatile residue. Under these tests the container must meet the requirements for nonvolatile residue under Physicochemical Tests — Plastics. USP 24 <661> also has test procedures for Polyethylene Terephthalate (PET) and Polyethylene Terephthalate G (PETG).

 

Since there are no USP monographs that specifically address closures, USP <671> and <661> are used to ensure package integrity in that area.