Pre-formulation Studies

By using very small amounts of active pharmaceutical ingredients (APIs) or druggable candidate compounds, the specialized pre-formulation studies provided by BOC Sciences can provide valuable information to inform the next steps in research.

Background

Pharmaceutical formulation design is the research work of pharmaceutical formulation design and formulation process optimization based on clinical medication needs, physical, chemical and biological properties of pharmaceuticals. Its purpose is to formulate the drug into a formulation suitable for production and clinical use. The main contents of formulation design include pre-formulation studies, selection of appropriate route of administration, selection of appropriate dosage form, selection of appropriate excipients and process, and optimization of formulation and preparation process.

Introduction

Pre-formulation studies refer to all the related work, such as understanding and measuring the basic physical and chemical properties of the drug, and studying the possible interactions between the drug and various related excipients, before designing the formulation.

Fig. 1 Early-stage pre-formulation studies

Meaning and Purpose

Pre-formulation studies are a critical step in the development of a successful pharmaceutical formulation. Pre-formulation studies provide the basis for selection and design of appropriate routes of administration, pharmaceutical dosage forms, formulations, processes, and quality control. The purpose of pre-formulation studies is to make the drug effective, safe and stable, and suitable for formulation and process requirements in industrial production. Data obtained from pre-formulation studies also provide an important foundation for understanding the potential pharmacokinetics of drugs in humans and animals.

Main Content

The main content of pre-formulation studies is to obtain various information required for formulation design, including the inherent physical and chemical properties of the drug (such as the physical properties of the drug, melting point, particle size, solubility, dissolution rate, crystal form, pKa, partition coefficient, surface properties, etc.), the stability of the drug, the compatibility of the drug and the excipients, the pharmacological action of the drug, the toxic and side effects of the drug, the irritation of the drug, and the absorption, distribution, metabolism and excretion of the drug in vivo.

Evaluated Parameters for Services

• Solid State Properties

Solid state properties include purity, crystal form, particle size and distribution, particle shape, fluidity, hygroscopicity, density, and compressibility. These features are very important. Because drug stability, safety, content uniformity and in vitro dissolution are often affected by these properties.

• Solubility

The solubility of a drug is one of the first factors to be considered in formulation design, as it affects the bioavailability of the drug. Regardless of the route of administration, the drug must have a certain water solubility in order to be absorbed by the body and have a therapeutic effect. If the solubility of the drug is lower than the expected value, it is necessary to consider adopting suitable methods to increase its solubility.

• Dissolution Rate

The dissolution rate of a drug is one of the important parameters because it may affect the absorption of the drug in the body.

• Partition Coefficient

Partition coefficient (P) refers to the ratio of the concentration of a drug in two immiscible solvents when it reaches a dissolution equilibrium. LogP is a measure of the lipophilicity of a drug. The larger the LogP value, the better the lipophilicity of the drug, and the smaller the LogP value, the better the hydrophilicity of the drug. In general, drugs with larger LogP values are more easily transported and absorbed through cell membranes.

• pKa

The degree of drug dissociation has an important impact on the formulation of the drug as well as its kinetic parameters. Typically, the degree of drug dissociation strongly depends on the pH of the drug-containing medium. Depending on the pH, the drug will exist as an ionized or non-ionized species.

• Stability Study

Heat, light, oxygen, moisture, pH, and excipients can all have a significant impact on drug stability. By studying the stability of the drug, the formulation composition, preparation process, selection of excipients and stability additives, and packaging and storage conditions are determined.

Fig. 2 Stability Studies

• Drug-excipient Compatibility Study

Potential physical, chemical, or biological interactions between the drug and excipients may affect the chemical properties, in vivo absorption, and stability of the drug. Therefore, understanding possible drug-excipient interactions is critical for selecting appropriate excipients.

BOC Sciences supports pre-formulation research in collaboration with clients worldwide. We can communicate, analyze and interpret research results to support our clients' research needs.