Preparation Quality Research

BOC Sciences has an experienced team of CMC experts familiar with various regulations and guidelines to support pre-prescription studies and drug formulation studies for global clients.

The three most important attributes of drugs are safety, efficacy, and quality control. Quality control corresponds to pharmaceutical research, which is related to CMC, which is the basis for drug safety and efficacy research, and is also the cornerstone of the entire drug development.

Pre-formulation Studies

Pre-formulation studies refer to the understanding, analysis, utilization and improvement of a series of basic physical, chemical and formulation properties of a drug before designing a formulation. The basic physical and chemical properties of drugs include chemical structure, melting point, crystal form, solubility, dissolution rate, partition coefficient, acidity and alkalinity, salt type, and spectral characteristics. The formulation properties of drugs include particle size, crystal shape, crystallinity, purity, hygroscopicity, fluidity, compressibility, and the interaction of excipients. Pre-formulation studies are generally conducted after the source of the drug, the pharmacological and pharmacodynamic effects of the drug, and the subjects and doses to be treated are known.

Fig. 1 Drug quality research

Analytical Method Development

Since there are many dosage forms of preparations, when researching new drug preparations, the requirements of the corresponding preparations in the pharmacopoeia of various countries should be followed.

1. Trait Item

The properties of the preparation mainly reflect the unique physical properties of the drug, such as appearance, color, odor, solubility and its physical constants.

2. Identification Item

The identification test of a drug is used to identify the authenticity of a drug, and is generally used as the primary item in drug testing. Chemical methods, spectroscopic methods, and chromatography methods are commonly used methods for preparation identification.

3. Check Items

There are many inspection items for preparations, which vary with different dosage forms. The inspection items for solid preparations mainly include weight difference, content uniformity, dissolution and release, and related substances. The inspection items for liquid preparations mainly include visible foreign bodies, solution color, clarity, endotoxin, sterility, microbial limits, and related substances.

The related substances in medicines refer to impurities other than the main components. Impurities in preparations include raw materials, intermediates, decomposition products, by-products, polymers and isomers brought in during the synthesis of APIs, degradation products generated during preparation and storage, transportation and use of preparations, and degradation products resulting from drug-drug and drug-excipient interactions. Since the presence of these related substances will affect the purity of the drug, and may cause toxic and side effects, the quality control of related substances is an important aspect of drug research and development. Since the content of these related substances is generally small, in order to strictly control the related substances, it is necessary to select an analytical method with strong specificity and high sensitivity. Spectroscopy and chromatography are indispensable tools for impurity detection.

Analytical Method Validation

The purpose of analytical method verification is to prove that the analytical method used can achieve the intended purpose, is suitable for the requirements of the corresponding testing items, and ensures that the measurement results are accurate and reliable. Analytical methods should be validated according to the characteristics of the drug product and the requirements of the ICH and Pharmacopoeia of each country.

Steps for Method Validation

• Preliminary determination of analytical method
• Develop a verification plan
• Carry out verification
• Collect experimental records and maps
• Submit a verification report
• Whether the evaluation method has passed the verification

Items that need to be verified include identification test, limit or quantitative inspection of impurities, content determination of active ingredients in preparations, determination of other ingredients in preparations (preservatives, degradation products, etc.), dissolution and release degree inspection, bacterial endotoxin detection, microbial testing, content uniformity testing, etc.

The content that needs to be verified includes accuracy, precision (including repeatability, intermediate precision and reproducibility), specificity, limit of detection, limit of quantification, linearity, range, durability, system suitability, etc. The specific verification content is subject to the requirements of the Pharmacopoeia.

Stability Study

Stability refers to the ability of a drug to retain its physical, chemical, biological and microbiological properties.

The stability study obtains the regularity of the quality characteristics of the drug substance or preparation over time under the influence of various environmental factors (such as temperature, humidity and light, etc.) through the verification of the analytical method, which provides a basis for the determination of the prescription, process, packaging, storage and validity period, thus ensuring that the drug meets the Safe, effective and quality controllable requirements. Stability research is one of the main contents of drug quality research. The stability study of preparations has the characteristics of stages, starting from the early stage of research and development and running through the whole process of drug research and development.

BOC Sciences has rich experience in pharmaceutical preparation quality research, focuses on details, and provides customers with stable and high-quality preparation quality research services.