Formulation Characterisation
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DISSOLUTION
Dissolution testing is an in-vitro test method designed to investigate the dissolution behaviour of a product under controlled conditions in a medium which might be formulated to mimic the biological environment of e.g., the stomach (simulated gastric fluid), gastrointestinal tract (simulated intestinal fluid), the mouth (simulated saliva), or in some circumstances across the skin. Additionally, water or various pH buffer solutions may be used.
Dissolution studies are conducted by placing a tablet or capsule in an apparatus which consists of a number of vessels containing the dissolution medium and maintained at a target temperature (typically, 37ºC). Each bath is stirred at a specified rate (e.g., 50 r.p.m. ) and the medium is sampled periodically and tested for the presence of the active drug by HPLC or on-line UV analysis. Hence, a dissolution profile is constructed detailing the amount of drug released from the tablet / capsule over time. Dissolution testing is a classic product performance indicator within the pharmaceutical industry, and may be used in quality control to indicate the consistent release of an active drug (within batch and batch-to-batch consistency). Dissolution profiles are also commonly used in drug product development.
STABILITY STUDIES
Storage stability evaluations are used to understand the stability of a product or material when stored in various packaging configurations for specified periods of time under a range of specified environmental conditions (temperature, relative humidity). Samples are periodically pulled from storage and analysed ? typically via HPLC (chemical stability ? potency and impurity assay) and dissolution testing (product performance testing), but also other methods as appropriate to the molecule. Physical stability (crystallinity determination, polymorphism determination) may be of particular interest in some instances. Any changes identified may be indicative of an unstable product.
During development, short term studies are typically carried out on multiple formulations to help determine the optimum final product. Subsequently, longer term studies involving the finished product contained in the final packaging are used to determine product shelf life.
RESIDUAL SOLVENTS ANALYSIS
The FDA guidance on this issues states Here that: "Since there is no therapeutic benefit from residual solvents, all residual solvents should be removed to the extent possible to meet product specifications, good manufacturing practices, or other quality-based requirements. Drug products should contain no higher levels of residual solvents than can be supported by safety data."
Given that virtually all (if not all) pharmaceutical manufacturing processes involve the use of solvents at some stage, the need to determine and control the level of residual solvent is clear.
VOLATILES
Many products can be exposed to a wide variety of volatile substances both pre- and post-final production. For instance, see This Article by John J Manura who reports that volatile emissions from synthetic materials can migrate into the finished consumer product, causing concern to the food and pharmaceutical industries.
W.J. Sichina and R.B. Cassel report Here that even a small level of volatiles (e.g., less than 1% w/w) can have a major impact on the processing of polymers. This issue can also affect the injection moulding or blow moulding processing. Sichina and Cassel further comment that the shelf life and cosmetic properties of pharmaceutical materials are strongly affected by the low levels of moisture contained in the compounds.
POTENCY ASSAY / IMPURITY ASSAY
In industries where quality is a bar that you can't go under, the need to be confident that your product meets your specification is undisputed. Two such key product parameters are the potency assay / purity assay of the active pharamaceutical ingredient.
Often such requirements are also driven by the regulatory authorities, for instance the FDA guidelines state Here: "The physicochemical and biological properties of the drug substance that can influence the performance of the drug product and its manufacturability, or were specifically designed into the drug substance (e.g., solid state properties), should be identified and discussed (by the license holder).
SUPPORTING MANUFACTURING PROCESS VALIDATION
As products are developed, control of the associated manufacturing processes becomes more critical. Understanding the criticality of the various parameters - where there is scope for flexibility versus where there is no such scope - becomes key. In the pharmaceutical industry this need is enshrined in the regulatory guidelines. For instance, the FDA states Here: "Process validation is a requirement of the Current Good Manufacturing Practices Regulations for Finished Pharmaceuticals ... Although the particular requirements of process validation will vary according [to] ... the nature of the ... product ... and the complexity of the process, the broad concepts [have] general applicability."
In order to validate these processes, a range of analytical techniques will be required.
