Effect of primary packaging on drug stability of solid dosage forms

A stimuli article on The Effect of Primary Packaging on the Physical Degradation of Metformin, Lisinopril, and Simvastatin Solid Doses During Patient Use When Stored at Different Temperature and Humidity Conditions has been published by Nair et al. in Pharmacopeial Forum 42(4) [Jun-Jul 2016].

The Stimuli article was prepared "based on the study published by the Healthcare Compliance Packaging Council on in-use stability of three commonly used drugs. The purpose of this Stimuli article is to draw attention to possible drug degradation during typical prescription cycles for products dispensed in standard high density polyethylene (HDPE) bottles and polypropylene (PP) pharmacy vials. The frequent opening of the bottles and vials for dosage access and tablet consumption exposes drugs to moisture and light. The physical degradation occurring to the product during the patient prescription cycle is presented and discussed. Products dispensed in blister packs remained unexposed until accessed due to the nature of the unit-dose packaging format and are, therefore, least affected during the usage period. It was observed that only in unit-dose blister packaging using barrier films (PVC/Aclar® or PVC/PVdC) did the products remain stable, even at high humidity conditions."

Drug manufacturers conduct stability studies according to regulatory requirements and recommend storage conditions. The stability data and the established shelf-life criteria are mandatory for medicinal products to be authorized by the competent authority.

These stability studies are typically valid for sealed containers (apart from in-use stability testing for medicinal products in multidose containers). Pharmaceutical products are packed at the manufacturer´s sites in, for example, unit-dose packaging intended to reach the patient so that individual drug units are protected until consumed by the end user.

However, it is common practice, for example in the U.S., to use bulk packaging for solid-dose distribution requiring repacking of the drugs into patient ready or unit-of-use formats. Therefore, the protection provided originally by the manufacturer is only effective until it reaches pharmacies, when the packaging is opened for the first time.

According to the article published "The common form of repackaging in a retail pharmacy is either high density polyethylene (HDPE) bottles or traditional amber polypropylene (PP) vials." The container integrity of these multi-dose packages is compromised  when they are first opened to consume the product. With every opening of the packaging all of the remaining tablets (or capsules) are exposed to air and moisture. If the packages are stored in the bathroom with usually high humidity levels, this could increase product degradation.

The presented systematic study evaluates the extent of drug product degradation occurring during typical use and whether such degradations can be prevented by using unit-dose barrier-blisters. The physical attributes of the drugs studied were moisture content, hardness and disintegration time.

The summary of findings states that: "Overall, in all three investigated drugs, maximum degradation was observed with the product packed in HDPE bottles, followed closely by low barrier PVC blister packs and PP pharmacy vials. Products packed in medium barrier PVC/PVdC and high barrier PVC/Aclar® blister packs remain virtually unchanged."

After registration on the USP Pharmacopeial Forum website you can read the complete stimuli article.

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