title: Proper Accounting for Surface Area to Solution Volume Ratios in Exaggerated Extractions.
abstract: When drug products contact plastic manufacturing components, packaging systems, and/or delivery devices, leachables from the plastics can accumulate in the drug product, potentially affecting its key quality attributes. Given practical issues associated with screening drug products for leachables, potential leachables are frequently surfaced as extractables revealed in extraction studies. To facilitate extractables discovery and identification and to shorten extraction times, extraction studies can be exaggerated and/or accelerated. One means of exaggerating an extraction is to increase the test article's extracted surface area to extraction solution volume ratio (SA/V), as it is generally accepted that an extractable's concentration in an extract is proportional to SA/V in a 1 to 1 manner. However, as the relationship between an extractable's concentration and SA/V depends on the extractable's plastic/solvent partition coefficient (kp/l), the effect of SA/V on the extractable's concentrations can be either under- or over-estimated if a 1 to 1 proportion is used. This article presents the theoretical relationship between SA/V, concentration, and kp/l; illustrates theory with a case study; and suggests proper exaggeration strategies.LAY ABSTRACT:When drug products are manufactured, stored, or delivered in systems that contain plastics, substances can be leached from the plastics and remain in the drug product, where they might affect the product's key quality attributes. To discover and identify these leached substances, the plastics are extracted under laboratory conditions and the extracts are appropriately tested. To facilitate this process, extracts may be generated under laboratory conditions that exaggerate or accelerate the drug product's clinical conditions of manufacturing or use. The proper use of the ratio of the extracted item's surface area to the volume of the extracting solution as an exaggeration parameter is discussed in this paper.
authors.affiliation: Baxter Healthcare Corporation, Round Lake, IL dennisjenke@triadscientificsolutions.com.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Jenke
authors.affiliation: Baxter Healthcare Corporation, Round Lake, IL.
authors.forename: Barrett E
authors.initials: BE
authors.lastname: Rabinow
mesh_terms: D005591:Chemical Fractionation / Q000379:methods*; D004340:Drug Contamination; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004349:Drug Packaging; D004867:Equipment Design; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010969:Plastics / Q000737:chemistry*; D015203:Reproducibility of Results; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations; D010969:Plastics
keywords: Design of Extraction Studies; Exaggerated extraction; Extractables; Surface area to solution volume ratio