EXTRACTABLE AND LEACHABLE & SORPTION
ABOUT EXTRACTABLE AND LEACHABLE & SORPTION
Virtually all products placed on the consumer market are
packaged in different material packaging, seeking to offer the best protection
to the product. The protection involves several aspects, such as: exposure to
light, shocks, oxidation, refrigeration, ambient temperature, among others. The
concept of packaging is to be of inert material which does not interact with
the product packaged therein. The packaging of the Pharmaceutical industry
differs in some properties of the Food industry, or other products in this way classifications
Primary Packaging: Primary Packaging: it is conceptualized as the packaging material in direct contact with the final product. In this contact the compounds may migrate to the packaging or be attracted to the packaging. Such situations are evaluated with the studies of Extractables, Leachables and Sorption.
Active-Excipient Interaction: the concern of the migration of the package to the product resides when the administration of the drug which can undergo changes in the absorption process, therefore, of its effectiveness.
RDC No. 73, dated April 7, 2016, instills control over possible and likely contaminants of the primary packaging that are likely to migrate and / or interact with the formulated product in contact with the primary packaging.
· Extracts: Compounds extracted from the packaging, either by aggressive solvents, contact time or temperature, that is, critical conditions to those found by exposure of the drug in storage. The objective is to detect such substances with the potential to migrate to the product in the packaging.
· Leachable: They are compounds present and detected in the primary packaging with the potential to migrate into the drug during storage. Extractable compounds may not be identified in the respective assay, but on contact with the drug formulation may have detectable substances. Also, in the leachable, it is possible to predict interaction of the substances from the extractables with the components of the formulation packaged therein.
· Extractable and Leachable: extension of the study of degradation impurities (RDC 53). They involve volatile, semi-volatile, non-volatile and metals analysis as the basic principle. Each packaging material has its peculiarities, as well as, the preparation of the study involves from simple analytical techniques as a measure of pH to complex and exclusive. It is fundamental study to ensure the quality and reputation of the pharmaceutical company's product.
· Sorption: Sorption is understood to mean the migration of the drug compounds into the package depending on the time or conditions of the package. The Sorption effect may result in a reduction in the amount of the active ingredient or excipients, alter the pharmacological balance and weaken the protection, for example in a gastro-resistant product. This evaluation is complex not only in the sense of changing concentrations, but also in the possibility of interaction with the primary packaging in its components. For the purposes of this study, we searched for the presence of active (s), placebo, coatings, among others.
The analytical techniques are based on the characteristics of each package, bibliographic research, composition sent by the manufacturer, packaging storage, collection and transport, among others. For such situations the T&E Center issues a questionnaire to collect as much information as possible to define the best analytical direction.
During the analytical test it may be necessary to extract or concentrate a possible contaminant signal, in this case one can use several methodologies such as: Liquid-Liquid extraction, SPE (Solid Phase Extraction), SPME (Solid Phase Micro Extraction), SBE (Stil Bar Extraction) and others for both organic and for metals.
Quantification Limits range from nanograms / mL, picograms / mL to phentograms / mL. The T & E center has equipment with sufficient detectability for even phentograms / mL. Among the analytical techniques, some are used, in the sense of searching:
· Volatile substances;
· Semi-volatile substances;
· Non-volatile substances;
· Inorganic Substances;
The analytical techniques will depend on the material and the circumstances surrounding the packaging:
· Gas-phase Chromatography (GC-FID-ECD-TCD-MS-Head Space);
· Liquid phase chromatography (UPLC or HPLC-UV / Vis; Fluorescence; ELSD);
· LC-MS / MS: Mass Spectrometry coupled to HPLC or UPLC;
· ICP-OES (Induced-Simultaneous and Sequential Plasma);
· AA - (Atomic Absorption) and FC (photometry of flame).
· TOC; DSC; IVFT; UV / Vis; High resolution microscopy, wet testing; among others.
· Determination of peak purity using DAD.
Validation of the methodologies applied to impurities detected:
In order to follow a validation procedure according to the current ANVISA standard it is necessary to know the impurity released or interacted with the product packed there. In extractables, if the impurity is identified and it is marketed, the validation is done with a method indicative of stability. If not, one can define a general method for the instrumental or other analysis, and quantify the product by response factor or percentage area, if analytical technique allows it.
In the case of Leachable and Sorption, it is important to use the validated method indicative of stability, for analysis of the packaged product, as well as to distinguish possible interactions of the impurities from the Extracts with the formulation packed therein.