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By Adrian [email protected]
Pharmaceuticals are subject to a variety ofdegradation pathways that compromise drugsafety and shelf-life. By far the greatestdegradation is caused by hydrolysis andoxidation. However, other mechanisms
include racemization, photodegradation, elimination, andcomplexation. A number of active packagingcomponents are available to help maintainpharmaceutical integrity; however, determining theoptimal solution requires a calculated analysis that joinsthe expertise of packaging engineers and pharmaceuticalformulation chemists.
Sorbents such as desiccants and oxygen absorbersrepresent a class of active packaging components thatcan be used to guard against the effects of degradation.These ensure the integrity of packaged pharmaceuticals.Sorbents are considered“active” because theyrespond to changes in theheadspace of packagingrelative to outsideconditions. Packagedsorbents are manufacturedfrom silica gel, molecularsieve, and a variety ofo x y g e n - a b s o r b i n gcompounds.
Active sorbents have highadsorbing capacity andtake up little space. Whenincorporated successfullyinto a package, they cansignificantly reduce therate of degradation,resulting in an improvement in pharmaceutical quality,safety, shelf-life, stability, and usability.
Sorbents come in different delivery formats, includingcanisters and packets, as well as a new compresseddensity format. Determining the correct active formularequires manufacturers to consider a variety of factors.
Modeling MoisturModeling MoisturModeling MoisturModeling MoisturModeling Moisture and Oxygen Ingre and Oxygen Ingre and Oxygen Ingre and Oxygen Ingre and Oxygen IngressionessionessionessionessionTo optimize package protection for solid-dose formulations,pharmaceutical manufacturers need to employ moistureand oxygen ingress modeling techniques to analyze therates of degradation for a given pharmaceutical. Therationale behind modeling is based on a number of factors.Oxidative changes can cause a loss of pharmaceuticalpotency after several weeks, whereas two to three yearsof shelf-life may be required depending on distributionchannels. Modeling also determines steady-state levelsof oxygen within bottles, moisture permeation across bottlewalls and material permeability.
Ingress modeling provides a calculated moisture oroxygen ingress value using established Moisture VaporTransmission (MVTR) and Oxygen Transfer (OTR) rates.MVTR and OTR rates are applied to the proposedpackage and, with the inclusion of other sources ofmoisture or oxygen, are used to determine the appropriateamount of sorbent material to be used.
Desiccant and oxygenabsorber requirementcalculat ions re ly oninterdependent dynamicmodeling, which judgesthe interact ion ofpackage permeabi l i tywith the ad-sorption andde-sorption properties ofthe pharmaceut icalformulation.
Ingress modeling resultsand related sorbentproduct recommendationsallow packaging engineersand formulation chemiststo quickly understand what
their theoretical sorbent requirement will be for a proposedpackage. It also allows them to demonstrate thesefindings using a small-scale, “proof-of-concept”accelerated stability test.
Ingress modeling requires specialized equipment as wellas skilled analysis by people experienced in packaging
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challenges and analytical chemistry. It is crucial to find apackaging solutions provider proficient in both of theseareas of expertise.
Examining the Whole PrExamining the Whole PrExamining the Whole PrExamining the Whole PrExamining the Whole ProcessocessocessocessocessWhen shaping a degradation-prevention program, it isalso critical that manufacturers consider the wholemanufacturing process. What might work in one part ofthe operation may not work at another end - solutionsdetermined upstream may have unintendedconsequences downstream.
For example, ingress modeling may propose a two-gramunit sorbent that does not fit into the neck of a proposedpharmaceutical bottle. Another critical consideration isthe type of automation found in a packaging line. Asorbent format may not work at high speeds with certainautomated equipment. Other times, a “double drop” ofsorbents may be required, depending on the bottledimensions, or the pharmaceutical.
An active packaging solution must consider all parts ofthe manufacturing process, from the pharmaceuticalformulation to the packaging environment and to thedistribution chain. When developing the optimumpackage protection, the best approach to take is a multi-disciplinary one that considers the knowledge andexperience of packaging engineers, formulationchemists, analytical chemists, and the sorbent supplier.
Consider Changing PrConsider Changing PrConsider Changing PrConsider Changing PrConsider Changing Protection Strategiesotection Strategiesotection Strategiesotection Strategiesotection StrategiesPharmaceutical manufacturers often assume that it is timeconsuming and expensive to change strategies once anactive packaging protocol has been established andapproved. This is not typically true. In fact, changingcourse may significantly streamline operations andimprove product quality, and often can be more cost-effective. The most time-consuming aspect of switchingstrategies is finding out what needs to be done.
Current FDA guidance hasmade changing desiccant,or oxygen absorber,formats a relatively simpleprocedure. Often it is asimple matter of an annualreporting change. It isimportant; however, to workwith a packaging partnerwho understands theregulatory roadmap. Allproducts should be 21CFR-compliant and supported by a Type III Drug MasterFile (DMF) on file with FDA.
Protecting pharmaceuticals from degradation is importantto ensure commercial success. When used appropriately,active packaging is an important part of the completesolution. As with any evolving technology, a change mayappear daunting but can, in fact, improve operations. Thebottom line is to consider the whole gamut of factorsinvolved in pharmaceutical degradation, and everyaspect of upstream and downstream processing.Calculating these factors with a modeling system,supported by a knowledgeable partner, can lead to amore shelf-stable, and safer, product.
Adrian Possumato is the Pharmaceutical MarketBusiness Development Leader with MultisorbTechnologies, Inc. (Buffalo, NY). He works closelywith drug innovators and generic pharmaceuticalmanufacturers in their R&D, quality, regulatory,engineering, and manufacturing departments todetermine the best selection of packaged sorbentsto stabilize pharmaceutical formulations. He hasover 15 years of experience in the pharmaceuticaland chemical industries.
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