Physicochemical property tests are integral to the verification, manufacturing support, and lot release programs for pharmaceuticals and biologics. It is essential that certain physical and chemical properties do not vary between or within lots, as they can determine critical compound features like drug delivery and absorption of the product in vivo. Pacific BioLabs has established a history of reliable testing of key physicochemical features for over 25 years. We offer a comprehensive suite of testing services that we will tailor to your lot release program, based on manufacturing and quality control needs. PBL tests for: appearance, pH, moisture content, osmolality, viscosity, optical activity, and spectral analysis.
Testing Services for Physicochemical Properties
As outlined by USP <790> Visible Particulates in Injections, all products intended for parenteral administration must be visually inspected. This ensures that all tested solutions are essentially free of visible particulates. The presence of these extraneous undissolved particles may indicate foreign contamination, loss of sterility, and may thus necessitate lot rejection. As such, it is important to monitor particulate matter and set-up appropriate controls. Additional presentation attributes including compound clarity/opalescence, turbidity and color may also be tested for conformance to client specifications.
Pacific BioLabs provides quick and accurate testing for pH, in accordance with USP <791> pH. This will determine whether the sample’s acidity/alkalinity meets the client’s expected specifications. The pH of a small molecule pharmaceutical or biologic formulation can significantly affect its stability, solubility, and in vivo delivery, making this test a crucial element of any lot release program.
PBL and its dedicated staff possess extensive experience in moisture content testing, following USP <921> Water Determination. At Pacific BioLabs, water content is determined using the Karl Fischer titration method – an industry standard. A large variety of pharmaceutical and biologic products contain water as hydrates (water of crystallization) or in adsorbed form (surface water). The degree of water contained can influence the therapeutics’ shelf life, activity, and quality, thus requiring compliance to a predetermined specification.
Osmolality is another important factor of lot release for a developed drug and is defined as the total number of solute particles per kilogram of solvent. Per USP <785> Osmolality and Osmolarity, Pacific BioLabs uses freezing point technology to test the osmolality of prepared solutions to ensure correct isotonicity, consistency, formulation, and product stability. Unintended osmolality parameters, such as hyper- and hypo-osmotic conditions, may compromise the desired delivery profile of the therapeutic, and in some cases, may even cause severe irritation upon administration.
A fluid’s resistance to flow, measured as viscosity, is a principal component of lot conformance. Pacific BioLabs provides robust viscosity testing using rotational methods, as outlined in USP <912> Viscosity – Rotational Methods. Viscosity is fundamental to a formulation’s intended propagation and activity, and may be used as a benchmark for compound concentration or degradation.
Many pharmaceutical compounds are chiral and hence optically active, given that they rotate plane polarized light. Following USP <781> Optical Rotation, Pacific BioLabs offers measurements using polarimetry for therapeutics such as antibiotics, dextrose, and steroids. The measure of optical activity of the provided solution can then be used by the client for many different aspects of a lot release program. By comparing with predetermined target specifications, polarimetry may be used to detect impurities or to determine the concentration of the intended chiral drug product. Furthermore, the optical rotation measurements may be used to verify that the stereospecific methods or separation of racemic mixtures consistently isolates the target molecule.
The unique absorption spectra of chemical/biochemical products can serve as a distinguishing physicochemical property of pharmaceuticals and biologics. Pacific Biolabs employs Ultraviolet-Visible (UV-Vis) and Fourier Transform Infrared (FTIR) Spectroscopy for target compound identification and concentration measurement. Spectral analysis may also be used to reveal impurities in the yield product. Pacific BioLabs follows the guidelines of <854> Mid-Infrared Spectroscopy and <857> Ultraviolet-Visible Spectroscopy.