Preparation Quality Research

Preformulation Study

• Preclinical evaluation of candidate compounds

  Items	Description
  Crystal forms	Crystal form determination by X- ray diffraction or DSC
  Solubility	Curve of solubility in acid and base solutions Solubility in organic solvent Solubility in compound solutions of different salt forms Solubility in simulated fasting intestinal fluid Solubility in simulated feeding intestinal fluid Solubility in simulated artificial gastric fluid
  Stability	Solution stability Solid stability Photostability pH stability
  Inherent properties	Dissociation constant and oil-water distribution coefficient

• Formulation selection related

  Items	Description
  Particle size distribution	Wet (more preparation required, preferably 1g) or dry method (data not as accurate as wet method)
  Solubility regarding pH changes	Solubility under water and solutions with pH values of 1.2, 4.5 and 6.8
  Hygroscopicity	Weight increase within 24 hours under different humidity conditions based on Chinese Pharmacopoeia
  Fluidity	Evaluation by angle of repose or Carr index
  Compatibility of ingredients	Interaction between APIs and selected ingredients
  Residual solvent	Method for detecting gas phase
  Microscopic observation, melting point, Pka, moisture, optical isomers, related substances, etc.

Method development

• Related substances are impurities in drugs except the main components. They may be raw materials, intermediates, reagents, decomposition products, by-products, polymers and isomers brought in during the synthesis of APIs, and degradation products produced during storage, transportation and use. As the content of related substances is generally small, it is very important to choose a detection method featuring good specificity, high sensitivity and great reproducibility. For drugs beyond standards, the methods of related substances will be developed according to drug properties, product characteristics, FDA, pharmacopoeias of various countries, relevant materials, and optimized to meet the requirements of ICH and pharmacopoeias of various countries for related substances. For drugs within national standards, it is not acceptable to refer automatically to existing national standards. The principle shall be “follow the category not the standard”, i.e., in the research of drugs within existing national standards, the safety and effectiveness of the developing products should be consistent with those of the products available on the market, and specific standards shall be set for specific categories.

Verification of analytical method

• Analytical methods shall be verified based on the characteristics of drugs and the requirements of ICH and pharmacopoeias of various countries.
  Method verification for enantiomerMethod verification for related substancesMethod verification for content uniformityMethod verification for content determination Method verification for microorganismMethod verification for dissolution determinationBacterial endotoxin test for drugsDetermination of impurity contentVerification contents include but are not limited to: specificity, linear range, accuracy, precision, detection limit, quantitative limit, durability and system adaptability. The specific verification contents shall be subject to the requirements of pharmacopoeias.

Stability Study

• Verification of analytical methods provides scientific basis for the determination of production, packaging, storage, transportation conditions and validity period of pharmaceutical products by investigating the laws of the changes of the properties of APIs and preparations with time under the influence of temperature, humidity and light, to ensure the safety and effectiveness of clinical medication. Stability evaluation is one of the main components of drug quality control research. It is closely related to drug quality research and the establishment of quality standards. The research on preparation stability is featured by phases and links all steps in drug R&D.
  Different placement conditions for stability study based on different formsDifferent investigation items based on different formsDifferent packaging materials based on different formsInvestigation of physicochemical properties and stability of drugs based on timeScheme design of stability study, project management, storage and detection of samples for stability study, data trend analysis, and evaluation of drug shelf life

Detection of microorganism

• Antibacterial test of drugsSterility test of sterilized preparationMicrobial limit test of non-sterilized preparations

Relevant laboratories

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