HPE Drug stability: What do we need to know?

BASICS Drug stability: the basics This article introduces the general definitions and concept of drug stability and the various factors affecting this Manisha Prajapati Thorsteinn Loftsson MS Pharm MSc PhD Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland Hospital pharmacists commonly prepare simple parenteral solutions by reconstitution of products from sterile drug powders and preparation of sterile admixtures containing two or more drugs into an infusion solution (for example, normal saline or 5% (w/v) dextrose solution). In some cases, the concentrate may be drawn up into syringes without dilution to provide pre-filled syringes for ready-to-use injection. In addition, hospital pharmacies sometimes produce complex parenteral solutions and large batches for specific groups of patients, which are stored for some time after sterilisation. In all cases, these manipulations can result in significant changes to the chemical and physical environment of the drug, which can influence the stability of both the drug and the overall infusion or injection. Pharmacists should be aware of the impact of solution media and storage conditions on shelf-lives and be knowledgeable about factors that affect drug stabilities. Concepts and definitions Stability Stability of drug products refers to the ability of the product to remain within established specifications regarding identity, potency and purity during a specified period. Stability is divided into three main categories: chemical; physical; and microbial stability (Table 1). Chemical stability Chemical stability involves breakage and/or formation of covalent bonds of the drug, usually referred to as the active pharmaceutical ingredient (API) that can result in loss of potency due to formation of inactive degradation products. For macromolecules or biologics, such as monoclonal antibodies, the degradation may involve conformational changes to secondary and tertiary molecular structures, altering the three-dimensional characteristics of the drug molecule. Chemical degradation can also result in formation of toxic degradation products. Physical stability Physical stability refers to changes in solubility (for example, due to changes in the crystal forms of drugs during storage) or appearance of the drug product (for example, colour changes (largely reflecting a change as a result of a chemical reaction)), as well as adsorption or absorption to containers and tubing (for example, polyvinyl chloride containers). Decreased solubility can result in drug precipitation in aqueous products such as parenteral solutions. Microbial stability Microbial stability refers to microbial growth and loss of sterility of the product. Shelf life Shelf-life is the time for the original potency (that is, 100%) of the API to be reduced to 90% (t 90 ) or, less frequently, to 95% (t 95 ). Definition of practical stability limits should take into consideration for each individual drug: therapeutic index, clinical use, safety and potency, pharmacodynamic and pharmacokinetic variabilities and total cumulative dose. 1 Some guidelines also directly require stricter limits. 2 In general, the British Pharmacopoiea specification for injections is 95–105% of the stated amount. For this reason, it is suggested that, where loss of the active ingredient is the critical parameter, a loss of 5% should constitute the maximum shelf life. 2 TABLE 1 The main categories of drug stability Category Example Chemical stability • Chemical stability relates to any changes in the chemical structure of the drug molecule resulting from chemical degradation • Changes in the breakage and/or formation of covalent bonds Physical stability • Physical stability refers to visual and sub-visual particulate levels in the infusion • No breakage or formation of covalent bonds • Changes in crystallinity and loss of crystal water resulting in decreased bioavailability Microbial stability 4 | 2019 | hospitalpharmacyeurope.com Microbial contamination of the drug product without loss of potency or bioavailability

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