Quantitative Analysis of Components in RLD

Generic drugs and Reference Listed Drugs (RLDs) must maintain the greatest consistency in dosage form, route of administration, safety, quality, and bioavailability. However, the originator usually only announce the types of excipients used in their prescriptions, but not the amount of excipients, which brings difficulties to the development of generic drugs. Alfa Chemistry's consistency evaluation service includes the quantitative analysis of components in the RLD prescription, helping you determine the dosage and composition ratio of the RLD components and guiding the development of your generic drug. In general, quantitative analysis of the RLD formulation composition begins with the identification of excipients that have a significant impact on the stability and performance of drug product. These excipients are usually called key excipients, including solubilizers and dissolution regulators for some special drugs, wetting agents for hydrophobic drugs, pH regulators/buffers for pH sensitive drugs, and stability/antioxidants in easily degraded/oxidized pharmaceutical preparations. Then, we perform the isolation and quantitative analysis of these key excipients.

Figure 1. A example of quantitative analysis of pharmaceutical drugs using Mass Spectrometry. (Wasen, S. V.; et al. 2021)

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Identification of Key Excipients

We provide identification services for some specific excipients such as sorbitol, mannitol, glycerol and PEGs that affect the bioavailability of drugs by affecting solubility, dissolution rate or permeability, because this process provides a basis for the subsequent characterization of the original drug Important information.

Quantitative Detection of Identified Excipients

At Alfa Chemistry, the quantitative detection of excipients includes two steps: the separation/extraction of excipients and the quantitative analysis of excipients.

• Separation of excipients
  Differential solubility method, filtration (using filters of specific pore size or molecular weight cut-off), high performance liquid chromatography (HPLC), high performance thin layer chromatography (HPTLC), size exclusion chromatography (SEC). Our expert team selects appropriate separation technique based on the amount of interfering components in the RLDs and their physical and chemical properties.



• Quantitative analysis of excipients
  Once the excipients are isolated, we perform the quantitative analysis using gravimetric methods or a variety of detection tools including UV-Vis, Refractive Index, Evaporative Light Scattering Detectors (ELSD), spectroscopic techniques such as Infrared or near-infrared spectrum.
• Gravimetric method: Suitable for quantitative detection of major insoluble excipients used in large quantities in preparations. After dissolving the soluble excipients, we measure the weight of insoluble matter after filtering and drying to calculate the amount of insoluble excipients such as microcrystalline cellulose in the RLDs
• HPLC and HPTLC: Available for the separation of small amounts of excipients such as stabilizers, surfactants and pH adjusters
• Size-exclusion chromatography: Efficient detection of high-molecule weight excipients such as polymers
• Elemental Analysis: Elemental analysis method can ensure that the dosage of excipients in the self-developed generic drug prescription is exactly the same as that in the RLDs. For liquid preparations, elemental analysis can be used to accurately quantify the content of excipients. For solid preparations, the amount of key excipients such as the disintegrant croscarmellose sodium used in the prescription can be quickly determined through the detection of sodium. For the commonly used binder sodium carboxymethyl cellulose and filler calcium hydrogen phosphate, element detection can also be used to conveniently determine their content
• Ion chromatography: Common anions in the RLDs that can be detected by ion chromatography include: F^-, Cl^-, Br^-, NO₂^-, PO₄^3-, NO₃^-, SO₄^2-, formic acid, acetic acid, oxalic acid, etc.