Excipient Compatibility Test of Generic Drug

The main purpose of the research on the consistency evaluation of generic drugs is the re-evaluation of the prescription and process of pharmaceutical preparations. The key to the formulation research of pharmaceutical preparations is to select the appropriate pharmaceutical excipients and the proportion of the excipients in the generic drug to ensure that the excipients can regulate the dissolution and release of active ingredients. Although excipients are inherent, they may interact with active ingredients and cause incompatibility. The selection of excipients will directly affect the quality, stability and curative effect of the final product. Therefore, the excipients compatibility study is of great significance in the consistency evaluation of generic drugs.

The Consequences of Excipient Incompatibility

• Changes in the appearance of the preparation
• Generation of related substances (impurities)
• Reduction of content of active ingredients
• Reduced therapeutic efficacy or physical stability

Aims of Excipient Compatibility Study

The purpose of the excipients compatibility study is to identify whether the excipients will affect the product performance. For example, whether the moisture contained in the excipients used such as microcrystalline cellulose, starch, lactose will affect the stability of the drug; whether the excipients from different manufacturers have different impact on the active ingredients.

Figure 1. The role of drug-excipient compatibility in the prescription process evaluation. (Lee, B. J. 2010)

Our Workflow of Excipient Compatibility Study

Alfa Chemistry provides excipient compatibility testing services, to ensure that the safety, stability and efficacy of your products will not be negatively affected by the selected excipients.

Research on the prescription composition of Reference Listed Drugs (RLDs)

We perform the investigation on the prescription composition of the RLD to determine the types and contents of excipients, as well as the storage conditions. According to the results of the RLD research, you can choose whether to conduct experiments:

• If the active ingredients are stable, and the requirements for excipients and storage conditions are not high, excipient compatibility test is not necessary;
• If the type of excipients used in your generic drug is consistent with those used in the RLD, excipient compatibility test is not necessary;
• If additional excipients are included in the prescription of your generic drug, we recommend to carry out excipient compatibility test for the added excipients;
• If you don't know the characteristics/properties of raw materials are, or the raw materials are unstable, or there are special requirements for excipients and storage conditions, it is recommended to perform excipient compatibility test;
• If the prescription composition of the RLD is not available, excipient compatibility test is required.

Excipient compatibility test process

1) First, we select several types of excipients, and mix them with active ingredients in a certain proportion.

2) A series of stability test are carried out at a high temperature of 60 degrees, strong light, and high humidity (RH75%, RH92.5%) according to the Guidance for Industry Stability Testing.

3) Sampling is conducted on day 0, day 5, and day 10, and the properties, content, and related substances of the drug are observed and investigated. In addition, we perform controlled experiments on the raw materials and excipients.

Figure 2. Evaluation of pharmaceutical compatibility. (Gholizadeh-Hashjin, A.; et al. 2021)

Excipient Compatibility Analysis Technology

Alfa Chemistry is equipped with the following advanced analytical instruments and tools to accurately evaluate the excipients compatibility.

• Separation and Quantification High Performance Liquid Chromatography (HPLC), Gas Chromatography (GC), Mass Spectrometry (MS), Size Exclusion Chromatography (SEC), and Gel Electrophoresis are employed to provide information on the chemical identity and stability of the API and excipients
• Physical Characterization: laser diffraction (for particle size analysis), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC), providing information on interactions that may alter the solid-state form of the drug or alter the physical properties of the drug product
• In vitro Release: Dissolution and in vitro release tests are performed to provide a measure of drug release from the product, allowing to assess the consistency of release from different formulations