The first step of generic drug development is to determine the prescription composition, component content and preparation process of RLD through reverse engineering, so as to achieve similar in vitro dissolution and finally achieve the same in vivo therapeutic effect.
Different preparation processes, such as granulation method, API and excipient addition sequence, API pretreatment, excipient addition method, and control of intermediate parameters (temperature, pH, etc.), may affect the dissolution of drugs in vitro and bioavailability in vivo, and also have a certain impact on the stability of drugs.
Our Services
The consistency evaluation of generic drugs requires a lot of manpower and material resources, and the quality, cost and approval speed of the product are the keys to profit. Formulation and preparation process are the keys to generic drug development, and reverse engineering is the foundation to develop generic drugs and ensure bioequivalence. Our company has extensive experience in RLD reverse analysis and is committed to helping generic drug manufacturers develop high-quality products as quickly as possible.
The preparation process is the key step that affects the quality of the drug, and the quality of the drug originates from design rather than inspection. Once the RLD composition is determined, the preparation process needs to be fully understood and controlled to ensure the continuous and stable production of formulations that meet process control and release standards.
Due to the nature of the specific API and excipients, RLD's formulation process may differ slightly from publicly available technology. And it is often due to these minor differences that improvements in product quality may be limited. For example, for solid oral tablets, conventional manufacturing processes include wet granulation, dry granulation or direct compression. However, the specific preparation process depends on the stability of the drug substance, the proportion of the drug substance to the total weight of the tablet, and the physical and chemical properties of the material, such as fluidity and compressibility.
Conventional Judgment Methods
- According to the physicochemical properties of the raw material
- Observe the slice of the tablet or the appearance of the preparation
- Investigate the disintegration behavior of the preparation in the medium
- Judge by the type of auxiliary materials, such as whether there is an adhesive
Our Research Methods
Our company has a professional RLD reverse engineering team and research platform. We can use a variety of instruments and advanced technology to quickly analyze the formulation, including raw materials distribution, coating layer composition and thickness analysis. Based on the study of API distribution and particle size in the formulation, the preparation process used in RLD can be deduced. Applicable dosage forms include traditional solid tablets, sprays, pellets, microspheres, etc.
By Raman imaging analysis of RLD, component distribution data can be obtained quickly. With Raman imaging, the microstructure of solid dosage forms can be quantified, including particle size, uniformity, and relative percentage content.
Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (EDS) can be used to analyze the element content and distribution of the solid preparation. We combine microstructure and composition analysis with drug dissolution or other macroscopic properties to comprehensively determine the formulation process of RLD.
Fig. 1. SEM-EDS is used for quantifying surface area coverage by MgSt on pharmaceutical tablets and particles. (Gunawardana CA.; et al., 2023)
Reference
- Gunawardana CA.; et al. (2023). Magnesium stearate surface coverage on tablets and drug crystals: Insights from SEM-EDS elemental mapping. Int J Pharm. 630:122422.
