A generic drug should have the same raw materials (APIs, major excipients) as the generic drug, no matter in composition or content. Therefore, the qualitative and quantitative analysis of the composition of the product is a very important part of the consistency evaluation. Alfa Chemistry provides principle component analysis of the Reference Listed Drugs (RLDs), helping you to promote the process control and quality assurance of your production process.
Advantages of RLD Principal Component Analysis
- Enhance the success rate of generic drug development
- Shorten the time for generic drug development
- Improve the pass rate of bioequivalence evaluation
Figure 1. The flow of pre-formulation study of drug. (Varu, R.; Amit K. 2015)
Our Services
To ensure that generic drugs can maintain the same type and dosage of excipients, the same crystal form, and the same preparation process as the RLD, Alfa Chemistry provides a complete analysis of the RLD principal component by performing the reverse engineering.
Formulation research
Analysis of prescription components: API, antioxidants, solubilizers, stabilizers, bacteriostats, isotonic regulators, fillers, suspending agents, thickeners, emulsifiers, pH regulators, etc.
Critical quality attributes of formulations: osmolality, zeta potential, headspace gas, encapsulation efficiency/drug loading, packaging materials, particle size and particle size distribution, etc.
API research
Key quality attributes of APIs: crystal form, solid state characterization, salt form, solubility, pKa value, particle size and particle size distribution, hydrate, amorphous form, density, etc.
Excipients research
Key quality attributes of excipients: crystal form, solid state characterization, peroxides, solubility, particle size and particle size distribution, hydrates, etc.
| Analysis Method | Our Services |
| ICP-OES/MS | Component analysis of the metal elements or special elements in the RLDs: SiO2, KHPO4, magnesium/calcium stearate, sodium carboxymethylcellulose, titanium dioxide, talcum powder, sodium hydroxide. |
| HPLC-CAD/ELSD | Analysis of excipients or APIs without UV absorption such as lactose, sucrose, mannitol, sorbitol, fatty acid, Tween, Span, various surfactants, polyetherimide, phospholipids. |
| IC | Analysis of various anions and cations such as phosphate, sulfate, nitrite, chloride, fluoride, ammonium, sodium, potassium, amino acids, etc. |
| Laser Particle Size Analyzer | Analysis of raw materials such as suspensions, gels, emulsions, special injections (liposomes, intravenous emulsions, microspheres, oil solutions, micelles, etc.). |
Hot Stage Microscopy
(TPM) | Determination of the microcosmic situation, shape, crystallinity, and polymerization state of preparations, APIs, and excipients. |
X-ray Diffraction
(XRD) | Structural, configuration, conformation and crystal form analysis of APIs, and excipients. |
| Raman Spectroscopy | Water content, amorphous and solvent residue analysis, crystal form identification, quantitative analysis of crystal form and crystallinity; phase transition research. |
Infrared Spectroscopy
(IR) | Research on grain size, crystal form, crystallinity, density, water content and optical rotation; research on ethyl cellulose or hydroxypropyl cellulose, microcrystalline cellulose and other excipients. |
Our Capabilities
APIs and excipients with different crystal forms may have different physical and chemical properties, which will affect the final performance of the product. Research on the crystal form of the RLDs can help you develop the ideal crystal form of your generic products. We provide a variety of technical tools to support a comprehensive research on the crystal form, distribution, morphology, particle size, etc. of APIs and excipients of the RLDs.
The particle size distribution (PSD) of APIs and excipients affects the quality of drug products, such as solubility, bioavailability, content uniformity, and stability, by influencing the flow, mixing uniformity, and compressibility of the intermediates outputted from the process, and ultimately the safety, efficacy, and quality control of the drug products. Alfa Chemistry provides professional RLD particle size study solutions to accurately detect the particle size and size distribution of APIs and excipients, and to help you select and prepare the ideal generic drug particle size.
Since most APIs have acidic and/or basic functional groups, their ionization state is controlled by the solution pH and acid dissociation constant (i.e., pKa). The degree of dissociation of APIs has an important impact on the prescription of generic drugs as well as their kinetic parameters, and is one of the physicochemical properties of interest. Alfa Chemistry provides professional solutions for API dissociation constant study, which can easily and quickly determine the pKa value of API with accuracy and reliability.
The consistence evaluation of the generic drug products starts with the comprehensive characterization of RLDs. We provide the prescription analysis services through literature analysis and qualitative analysis of RLD prescription components, including identification of APIs, excipients and other substances in RLDs.
Most of originator usually only announce the types of excipients used in the prescription, but not the amount of excipients, which brings difficulties to the development of generic drugs. We help to quantitative analysis of the ingredients in the RLD prescription, helping you determine the dosage and composition ratio of the the RLD ingredients. At Alfa Chemistry, the quantitative detection of excipients includes two steps: separation of excipients & quantitative analysis of excipients. Our experts are able to select the appropriate separation technique based on the amount of interfering components in the reference preparation and their physicochemical properties. For different dosage forms, we employ different detection tools for quantitative analysis.
Impurities in medicines can reduce efficacy, affect stability, and even cause side effects. One of the key requirements for pharmaceutical equivalence of generic drugs is to ensure that the impurity profile of the generic drug is as consistent as possible with that of the original drug. ICH guidelines divide impurities in drugs into three categories: organic impurities, inorganic impurities, and residual solvents. Our company provides highly specific and sensitive analytical methods for these three impurities in RLD.
Solubility is one of drugs' most critical physical and chemical properties. The release and dissolution of APIs largely determine the efficacy and safety of drugs. Excipients have a significant effect on API solubility and dissolution. Therefore, in the early stage of generic drug development, it is necessary to measure the solubility of raw materials and excipients in RLD at multiple pH. Our company generally uses the shake flask method to test the solubility of API and excipients in RLD under specified pH conditions.
Drugs must have adequate water and lipid solubility (water-oil partition coefficient) for them to be absorbed through the biofilm and exert their effects. Lipophilicity has a significant impact on drug absorption, distribution, metabolism, toxicity and pharmacological activity. Our company used shake flask and potentiometric titration to determine the lipophilicity of RLD.
Reference
- Varu, R.; Amit K. Opportunities and challenges to implementing Quality by Design approach in generic drug development. Journal of Generic Medicines. 2015. 7(1): 60-73.
