Our industry-leading scientists conduct preclinical and clinical stability studies on drug substance and drug products through our full-service solid state and chromatography/dissolution groups. We develop chromatographic, dissolution and solid state methods for material assessment and conduct accelerated stress testing on site with GMP ICH stability storage at AMRI sites or preferred vendors. Our experts guide you to the best solid form and dosage form for your API and help determine risks that may impact your development program.
Stress testing can reveal physical and chemical changes of the API or excipients that occur during processing and storage. We conduct high-temperature, high-humidity, light exposure, and mechanical (grinding and compression) stress studies to identify and quantitate physical and chemical changes. You can then assess risk and take precautions to control undesired changes in the API solid form, which may include modification of formulation components and/or manufacturing steps, and appropriate packaging configurations for bulk drug product intermediates and finished materials.
In Vitro Comparative Analysis
We can evaluate the performance characteristics of various drug products in a laboratory setting. Using tools such as dissolution, diffusion and disintegration, we can assess abuse deterrence through alcohol-induced dose dumping and bioequivalence. In vitro bioequivalence studies can be performed for various non-absorbed drugs, topical and oral drugs, locally acting emulsions and suspensions, and transdermal patches. In vitro comparative studies can also be used to demonstrate equivalency in manufacturing process or site changes, equivalency in products with multiple strengths, and marketing advantage.
We perform dissolution testing to reveal differences in performance during drug product development and as a validated control method for release testing. Dissolution rates are highly dependent on the intrinsic properties of the API solid form (e.g., solubility) and the process parameters used for drug product manufacture (e.g., particle size distribution, tablet hardness and friability). Therefore, characterization of the dissolution rates of different formulations in various media can guide excipient selection and identify critical process control parameters to achieve the desired release profiles for an immediate, controlled or modified-release formulation.
Our scientists have extensive experience developing and conducting dissolution studies for a broad range of drug products using both automated and manual sampling techniques. Various forms of equipment, as described in the United States Pharmacopeia (USP and USP ) for Dissolution and Drug Release are available including Apparatus 1 (baskets), Apparatus 2 (paddles), and Apparatus V (paddle over disk). Rotating disk (USP ) is available to study API solid form dissolution, using compacts with known surface area and powders. Sink and non-sink conditions, as well as precipitation can all be considered, depending on need.
Additionally, our scientists have expertise in the use of aqueous buffers and simulated biorelevant media, such as McIlvaine buffer to mimic Fasted State Simulated Gastric Fluid (FaSSGF), Fed State Simulated Gastric Fluid (FeSSGF), Fasted State Simulated Intestinal Fluid (FaSSIF), and Fed State Simulated Intestinal Fluids (‘FeSSIF and FeSSIF-V2’).
To assess membrane permeability for various combination products, our scientists employ side-by-side diffusion. Franz vertical diffusion cells are used to evaluate drug release from semi-solid dosage forms.
We leverage a wide variety of quantitation tools to measure concentration of the API in different media from various in vitro comparative analysis techniques. In situ monitoring via a UV dip probe may be used for selected media. When possible, we develop a non-validated UV-VIS method. HPLC methods can also be developed and used. We perform these studies under controlled conditions using sufficient replicates to allow for calculation of statistics.