Drug Solid-State Research Service Platform

 

Medicilon's pharmaceutical solid-state research service platform is dedicated to crystal form research services in the development of new drugs and generic drugs. It can provide salt form and polymorph screening, single crystal culture and structure analysis, crystallization process development, chiral separation and other services to assist global pharmaceutical research and development.

• Solid-state research on drugs is an essential part of the drug research and development process.  For innovative pharmaceutical companies, solid-state research is a magic weapon to promptly identify advantageous forms, expand the scope of patent protection, and extend the product life cycle.  For generic pharmaceutical companies, solid-state research is expected to break through the patent barriers of original research, improve the technical content of products, and obtain market entry benefits.  Therefore, developing the "right" solid form is a critical aspect of drug development.
  Medicilon's pharmaceutical solid-state research service platform is dedicated to crystal form research services in the development of new drugs and generic drugs. It can provide salt form and polymorph screening, single crystal culture and structure analysis, crystallization process development, chiral separation and other services to assist global pharmaceutical research and development.

Services Capabilities

• 1. Screening of Salt Forms and Polymorphs

  Improve key physical and chemical properties of drugsImprove drugabilityIdentify and decide to develop free base, salt or co-crystalDetermine the dominant crystal forms that can be developedLayout and breakthrough of crystal patents

• 2. Single Crystal Culture and Structural Analysis

  Confirmation of the molecular structure of API (stereoconfiguration, molecular conformation)Confirmation of crystal structureDetermine the unit cell parameters of a specified crystal form and provide standard XRPD spectraCombination of solvent and drug moleculesDetermine the chemical composition ratio of the compound

• 3. Crystallization Process Development

  Control of crystal form, crystal habit, and particle sizeYieldPhysical and chemical puritySolvent residue

• 4. Chiral Separation

  Selection of chiral separation resolving agentsSelection of solvents

• 5. Qualitative and Quantitative Analysis of Crystal Forms

  Qualitative and quantitative analysis of crystal forms of APIsQualitative analysis of crystal forms of raw materials in preparations

Typical Steps for Solid-State Screening and Evaluation

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Medicilon Solid-State Research Advantages

• 1. Senior Team with Extensive Experience

  Medicilon solid-state researchers have extensive experience in salt form/eutectic screening, crystal form screening, and crystallization process development.  The project leaders have all worked in the solid-state pharmaceutical industry for 5-10 years and are familiar with the regulatory requirements for drug crystal forms in the US and China’s registration regulations.  In addition, they have experience in more than 50 projects and are able to formulate optimal screening strategies based on material properties.

• 2. Technical Expertise, Focus on Cutting-Edge

  Medicilon is particularly good at the research and control of the solid form of drug molecules in raw materials and preparations.  In addition, Medicilon actively seeks breakthroughs and innovations in the latest technologies and continuously explores cutting-edge solid-state research technologies.

• 3. Whole-Process Management and Control Optimization Strategy

  From drug discovery to IND filing, one-stop pharmaceutical preclinical R&D services, Medicilon empowers the solid-state screening team with a more systematic crystal form (salt form) evaluation.  The solid-state research team and the medicinal chemistry, formulation, PK, PD and other teams work together to follow the molecule and consider whether the crystal form needs to be changed based on comprehensive factors and iteratively optimize strategies to accelerate the research process of new drugs.

Partial Project Experience

• Project	Develop Details	Current Progress
  Class 1 small molecule chemical drugs (NMPA & FDA Phase I application)	Salt form screening + Preferred salt form screening + Crystal forms of free bases screening	Completed, IND application has been submitted to the FDA and accepted.
  Class 1 small molecule chemical drugs (NMPA & FDA Phase I application)	Salt form screening + Crystal form screening	CDE’s implicit permission for clinical trials and FDA’s approval to enter clinical trials
  Research and development of Class 1 new drug ophthalmic preparations (non-CMC) and salt form screening research (non-application)	Salt form screening + Crystal form screening	IND application has been accepted
  Preclinical research on innovative drugs of S1P1 receptor inhibitor (Treatment of ulcerative colitis)	Salt form screening + Crystal form screening	IND application obtained clinical implicit approval from US FDA
  Class 1 small molecule chemical drugs (NMPA & FDA Phase I application)	Salt form screening + Preferred salt form screening + Crystal forms of free bases screening	Completed, GMP Production
  Class 1 small molecule chemical drugs (NMPA & FDA Phase I application)	Salt form screening + Crystal form screening	Obtained clinical approval from FDA
  Class 1 small molecule chemical drugs (NMPA & FDA Phase I application)	Crystal form screening	The clinical trial application was accepted by NMPA, and the clinical trial is implicitly approved.
  Class 1 small molecule chemical drugs (NMPA & FDA Phase I application)	Crystal form screening	Completed, GMP Production
  Class 1 small molecule chemical drug API and tablets (2 specifications, specifications to be determined) process development research (Supports NMPA and FDA declaration)	Salt form screening + Preferred salt form screening + Crystal forms of free bases screening	IND application was approved by the US FDA; the clinical application of HDM1002 for adults with type 2 diabetes obtained implicit permission from the CDE
  Class 1 new drug XX API process development research (NMPA and FDA declaration)	Salt form screening + Crystal form screening	Obtained implicit permission from CDE for clinical trials

Case Studies

• 01 Case Study - Salt Type Screening

  New Drug Project: MED220*
  A foreign company has a compound in the preclinical stage.  Since this compound has low solubility and cannot meet the in vivo exposure requirements, it is hoped to carry out salt screening work in order to select salt forms with better physical and chemical properties for subsequent development.
  
  Screening Result
  1. Select candidate salt forms based on the results of salt form screening and characterization, and factors such as ion safety level, polymorphic form, and thermal properties.
  2. To further evaluate the hygroscopicity of candidate salt forms, the solid-state stability and solubility are comprehensively evaluated together with the free state, and the dominant salt type with suitable properties in all aspects is selected.

• 02 Case Study - Crystal Form Screening

  Project Code: MED2*33
  
  Screening Result
  1. A comprehensive polymorph screening test designed based on compound characteristics resulted in a total of 11 new crystalline forms and amorphous forms.
  2. The new crystal forms discovered through physical and chemical property characterization and crystal form identification include 3 amorphous forms, 3 hydrates, 2 solvates, 3 metastable crystal forms and amorphous forms.
  3. The results of the study on the crystalline transformation relationship show that the non-crystalline Form A is stable under specific water activity conditions at room temperature, has good physical and chemical stability, has almost no hygroscopicity, and has a solubility that meets development needs.  It is recommended as the dominant crystal form for subsequent development and research.

• 03 Case Study - Particle Size Control

  Project Code: XYM23*1M
  The sample particle size is small, the fluidity is poor, and the electrostatic phenomenon is obvious, resulting in inconsistent in vitro dissolution behavior with the reference preparation, which has a great impact on preparation development.  Therefore, new crystallization processes were developed to increase particle size and meet formulation requirements.
  

  Batch number	Delivery quantity(***)	Delivery quantity (Solvent-1)	Delivery quantity (Solvent-2)	Amount of seed crystal	d90/μm	Yield
  009740-22-***	25.0 g	108.1 g	39.2g	0.5%	136.29	92.8%

  
  

• 04 Case Study - Crystallization Process Development (Preparation of Crystalline State)

  Project Code: MED23*3
  The sample is a certain salt, a foamy amorphous solid that easily absorbs moisture and agglomerates into oil.  Various crystallization methods were tried, but no crystals could be obtained, which was not conducive to subsequent process development and quality control.  Therefore, there is an urgent need to develop new crystallization processes to prepare crystalline states.
  

• 05 Case Study - Single Crystal Cultivation, Changing Crystal Habits

  Project Code: MLP2*01
  Conventional methods for single crystal cultivation include slow volatilization, gas-liquid penetration, slow cooling, and liquid surface diffusion.  In addition, there are reaction crystallization, pH adjustment crystallization, hydrothermal crystallization, addition of inorganic salts, addition of polymer crystallization, etc.  Based on the characteristics of the compound and the crystallization process, a targeted culture plan is developed.  A certain compound is crystalline with fine particles. It is easy to obtain sea urchin-like crystals, but it is difficult to obtain a single crystal analytical structure.
  

Learn more about "Drug Solid-State Research"

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  [Platform]Process Department Solid Form Screening Platform