Physical Hazards Assessment of Excipients

Pharmaceutical manufacturers must be able to provide useful information on excipient quality testing to demonstrate that inactive ingredients such as excipients do not affect the safety or efficacy of the drug. Some physical hazards such as choking and irritation can cause harm to humans, so physical hazard assessment is an important part of excipient risk assessment. To avoid some drug dosage forms causing swallowing difficulties or choking to patients, it is necessary to improve the flowability of the drug. Excipients such as flow aids, binders and lubricants are commonly used to add to APIs to improve their flow, wetting and release properties, accelerating the disintegration of orally administered drugs. Excipients are essential as a support for active ingredients in drug products, and they contribute to drug stability, shelf life, pharmacokinetics, bioavailability, appearance, and acceptability. However, for some products such as vaccines and inhalation formulations, excipients are a major cause of immediate hypersensitivity reactions. Clinical studies have shown that common excipients including gelatin, carboxymethylcellulose (CMC), polyethylene glycol (PEG) and PEG-related excipients such as propylene glycol (PG) frequently trigger hypersensitivity reactions in patients. Local irritation responses to excipients are often used as a preliminary assessment of the safety of excipients in the formulations. Therefore, allergenicity testing of excipients is performed to minimize cellular irritation and allergenicity.

BOC Sciences' complete excipient quality control services can help you identify and address potential physical hazards in excipients before your product enters into the commercial production. Based on the results of our assessment, you can select new excipients or optimize your current formulation to ensure that your formulation is stable, effective and consistent.

Physical Hazards Assessment Services

BOC Sciences' laboratory is specialized in the assessment of physical hazard of excipients to ensure that your excipients are compliant with the related regulations. We perform the flowability, moisture content testing to characterize excipients, thus avoid the drug dosage forms that can cause swallowing difficulties or choking to patients. Irritation testing is carried out to determine whether your excipient will cause local irritation.

Flowability Assessment

We provide flowability assessment of excipients by adding co-processing excipients to prepare the API containing compounds.

Our characterization services for flow properties of excipients and key properties of tablets:

• Emission Scanning Electron Microscopy (SME): Characterization of the size, shape and morphology of excipient powders
• Flowability measurements including bulk density and compaction density to obtain Hausner ratio and Carr index, static angle of repose

Figure 1. Assessment of pharmaceutical powders flowability. (Kkma, D.; et al. 2022）

Measurement of Moisture Content

The water or moisture content of excipients is important for the flowability of the drug. At low moisture content, water acts as a lubricant between particles of excipients and increases flowability, while at high moisture content, water increases cohesion through building stronger liquid bridges, thereby decreasing flowability. The flowability of the drug increases with increasing moisture content and the particles form larger, more spherical clumps. To ensure that tablets can be taken smoothly by patients, the moisture content of excipients must be measured and controlled. We provide dynamic avalanche behavior measurement to assess the moisture content of excipients.

Irritation Testing

BOC Sciences offers irritation tests for determining whether your excipient will cause local irritation in the skin, mucosal, or ocular tissues. Extracts of the test article are dosed or the test article is applied directly to the animal. The site of administration will be examined at 24±2, 48±2 and 72±2 hours after treatment. The irritant effect of the excipient is measured by observing irritation reactions such as erythema and edema.