How to Select Excipients in Drug Formulation?

The purpose of formulation development is to ensure that the drug is safe, effective, stable, and convenient to use. If the dosage form is improperly selected and if the prescription and process design are unreasonable, it will have a certain impact on the quality of the drug product, and even affect the drug’s efficacy and safety. Therefore, formulation research occupies a very important position in drug development. Excipients are the general term for other materials in preparations except for the main drug, and are an important part of pharmaceutical preparations. Below are a few guidelines for the selection of excipients in drug formulation.

General principles for the selection of excipients

Excipients can be selected according to the characteristics of the dosage form and the needs of the route of drug administration. The excipients used should not have an adverse interaction with the main drug, and should not affect the content determination of the preparation and the inspection of related substances. Also, the excipients required for the production of drugs must meet the requirements for medicinal use.

Compatibility research

The compatibility study of drugs and excipients provides useful information and reference for the selection of excipients in the prescription. Drug applicants should be fully aware of the interactions between excipients and excipients, and between excipients and drugs through preliminary investigations, so as to avoid choosing inappropriate excipients during prescription design. In some cases where relevant research data are not sufficient, a compatibility study should be conducted. For example, for oral solid preparations, several kinds of excipients can be selected. If the amount of excipients is large (such as diluents, etc.), they can be mixed at the ratio of main drug: excipients = 1:5. If the amount of excipients is small (such as lubricants, etc.), they can be mixed according to the ratio of main medicine: excipients = 20:1. The next step is to take a certain amount, use experimental methods of the influencing factors in the drug stability guidelines or other suitable experimental methods, and study on the properties, content, related substances. When necessary, the raw materials and excipients can be used to do parallel control experiments respectively to determine whether it is the change of the raw material itself or the influence of the excipients. If an excipient that interacts with the drug is used in the prescription, it is necessary to use experimental data to prove the rationality of the prescription.

Physical and chemical properties and dosage of excipients

The physical and chemical properties of active pharmaceutical ingredient excipients (including molecular weight and its distribution, degree of substitution, viscosity, properties, particle size and the change of its distribution, fluidity, moisture, pH value, etc.) will affect the quality of the preparation. For example, the change in the particle size and density of the diluent may affect the content uniformity of the solid preparation. Changes in the molecular weight or viscosity of the material may have a significant impact on the drug release behavior. The change in the chemical properties of the auxiliary material may be caused by the production process of the auxiliary material, or may be related to the change of the source of supply of the auxiliary material. Therefore, it is necessary to analyze the physical and chemical properties of the excipients in the formulation according to the characteristics of the formulation and the drug administration route. If the research proves that these parameters are very important to ensure the quality of the formulation, corresponding formulation or improvement should be made in order to ensure the stability of the quality of the excipients.

Therefore, for quality control indicators, researchers should pay attention to selecting appropriate sources of supply, and clarify the specifications and models of auxiliary materials. Understanding the route of administration of excipients in marketed drugs and their reasonable dosage range is an important part of pre-prescription research. This information can provide a scientific basis for prescription design. Drug applicants can search the FDA and other authoritative databases at home and abroad to understand the rational use of the examined excipients in the marketed drugs. In addition, necessary safety tests are required for certain physiologically active excipients, excipients that exceed conventional dosages and are not supported by literature, and excipients that change the route of administration.

About the author

Formulationbio is a leading manufacturer of excipients, serving the pharmaceutical industry to help it improve the performance of its products. We develop, produce and sell pharmaceutical excipients for solid, semi-solid and liquid dosage forms. Our excipients include: binders, colorants, diluents, disintegrants, lubricants, plasticizers, surfactants, sweeteners, fillers, emulsifiers, stabilizers and so on. In addition, we can provide preformulation, formulation, analytical and custom pharmaceutical excipients services to address the needs and formulation challenges of our customers.