Selecting the right solid-state form for your Active Pharmaceutical Ingredient (API) is a critical decision that can significantly influence the success or failure of a pharmaceutical product. The incorrect selection of a solid-state form can lead to a myriad of complications, including but not limited to poor bioavailability, which affects the drug’s effectiveness in the body, as well as stability issues that can result in the degradation of the active ingredient over time. These problems can subsequently lead to substantial delays and setbacks in your drug development process, potentially derailing timelines and increasing costs.
Our API polymorph screening service is meticulously designed to align with your specific goals, ensuring the elimination of suboptimal solid-state forms that often hinder early stages of drug development. This service is essential because different polymorphs of the same compound can exhibit vastly different physical and chemical properties, impacting not only bioavailability and stability but also manufacturability, which pertains to the ease and cost-effectiveness of producing the drug at a commercial scale.
Our service is powered by cutting-edge platform technologies and supported by a team of highly accomplished scientists with extensive experience in the field. We leverage advanced polymorph screening techniques that integrate industry-proven workflows, which have been refined and validated through years of research and application in the pharmaceutical industry. These workflows are complemented by our high-throughput capabilities, enabling the rapid and efficient discovery and selection of the most suitable solid forms for your API.
Our approach ensures that we can quickly identify and characterize all possible polymorphic forms of your API, allowing us to select the most stable and bioavailable form that meets your specific development needs. By doing so, we help mitigate the risks associated with poor solid-state form selection, ultimately facilitating a smoother, more efficient drug development process.
Furthermore, our polymorph screening service is designed to be comprehensive and customizable, tailored to meet the unique requirements of each project. Whether you are in the early stages of drug discovery or progressing through clinical development, our services provide critical insights and support to enhance your drug’s performance and manufacturability, ensuring that your development journey is as seamless and successful as possible.
Overview
Every API possesses many solid-state forms, with unique physicochemical properties that influence bioavailability, stability, and solubility, stability, manufacturability. To achieve success in preclinical evaluation, product development, and manufacturing, it is crucial to discover and thoroughly examine the optimal solid-state form for an exceptional balance of properties.
Renejix Advantages:
- Expedite the development and optimization of your drug molecules with our API analytical equipment and technologies
- Developed and refined dozens of chemicals in collaboration with a network of API manufacturers
- Collect data to comprehensively screen salts, crystal forms, and co-crystals
- Backed by a diverse team of seasoned scientists
Our Polymorph Screening Services
Comprehensive Crystal Analysis:
- Harness the power of high-throughput screening capabilities for comprehensive analysis
- Uncover ideal crystal form
- Conduct stability relationship assessments for reliable performance
- Scientists conduct solid-state nuclear magnetic resonance (NMR) spectroscopy for detailed structural analysis of complex solid forms.
- We utilize computational modeling to predict solid-state behavior and guide experimental design, reducing the need for extensive trial-and-error testing.
Unlock Co-crystals Capabilities:
- Utilize high-throughput screening capabilities to discover all viable polymorphs of an API, ensuring a thorough understanding of the compound’s solid-state landscape.
- Access an extensive library of reagents for versatile exploration
- Apply crystal engineering expertise to optimize co-crystal formation
- Property Optimization: We evaluate each polymorph for critical properties such as solubility, stability, and manufacturability, to select the form that offers the best balance for your drug product.
Solid-State/Polymorph Characterization:
- Comprehensive Characterization: We use a full suite of solid-state characterization techniques including: X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), Polarized light microscopy/birefringence, hot stage microscopy, scanning electron microscopy (SEM), Fourier Transform Infared (FTIR) Spectroscopy, Sorption isotherm analysis, Karl Fischer (KF) analysis, Vapor pressure analysis, Heat capacity measurements, Solubility relationships, Dissolution rate studies, Slurry conversion studies, and Bioavailability Pharmacokinetics.
- Form Selection Rationale: We provide a detailed rationale for form selection based on a holistic assessment of data, ensuring that the chosen form aligns with your product’s development goals.
Transform Amorphous into Crystalline Forms:
- Leverage high-throughput polymorph screening capabilities to identify crystalline forms
- Discover a diverse array of elements to drive successful transformation
- Unlock the true potential of amorphous compounds with precision and efficiency
Resolve Challenges:
- Utilize advanced characterization techniques to identify and understand new phases
- Accurately quantify phases for precise control and analysis
- Conduct comprehensive contaminant analysis for optimal purity and safety
Formulation Compatibility:
- Excipient Screening: We conduct excipient compatibility studies to ensure that the selected solid form remains stable and effective in the final formulation.
- Formulation Development: We work closely with formulation scientists to integrate the solid form into a robust and manufacturable drug product.
- Process Optimization: We optimize the manufacturing process to accommodate the solid form, ensuring consistent quality and performance.
Pseudopolymorphism (hydrates & solvates)
The chemical and physical properties of pharmaceutical solids also depend on moisture content. Many compounds undergo changes in hydration state with corresponding changes in ambient humidity. Because water vapor is present during virtually all facets of pharmaceutical development, a fundamental understanding of the relationship between water sorption and relative humidity is necessary. Water sorption isotherms are generated by monitoring water content as the relative humidity is manipulated. X-ray diffraction and thermal analysis are used to determine if different states of hydration exist. Compounds exhibiting multiple hydrated states are often referred to as pseudopolymorphs.
Polymorph Characterization
Renejix Pharma Solutions characterizes polymorphic active ingredients by determining the chemical and physical properties of each form. The thermodynamic hierarchy of the polymorphs is evaluated to provide insight into the stability relationships among the different polymorphs. The spectral and powder characteristics of each form are also determined. Solubility, dissolution rate, bioavailability and pharmacokinetics of each polymorph can also be characterized. An example of a stability hierarchy for a compound having three polymorphs is shown below. Under ambient conditions, generally only one polymorph is stable. All other solid state forms are metastable relative to the stable form. Characterization of polymorphs at Renejix includes determining the energy (or stability) relationship among different polymorphs of a given active ingredient to ensure you have stable low energy forms regardles of temperature.
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FAQs
Here are some frequently asked questions about Solid state screening
Solid state screening is a critical process in pharmaceutical development that involves the systematic investigation of a drug substance's polymorphic forms, salts, co-crystals, and amorphous forms. This screening is essential for identifying the most stable and bioavailable solid form of a pharmaceutical compound, which can significantly impact the drug's efficacy, stability, manufacturability, and patentability. The process utilizes various analytical techniques to characterize the physical and chemical properties of different solid forms.
Solid state screening is vital for drug development because the physical form of a drug substance can affect its solubility, dissolution rate, and bioavailability, all of which are crucial for effective drug delivery. Identifying the optimal solid form early in the drug development process can enhance drug performance, extend product shelf-life, and improve patient compliance. It also helps in patent formulation strategies and regulatory approval by ensuring the selected form is robust and reproducible.
A variety of analytical techniques are used in solid state screening, including X-ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Solid State Nuclear Magnetic Resonance (SSNMR), Infrared Spectroscopy (IR), and Dynamic Vapor Sorption (DVS). These techniques provide comprehensive data on the crystal structure, thermal properties, moisture interaction, and molecular dynamics of the solid forms.
A CDMO approaches solid state screening with a systematic and phase-appropriate methodology, tailored to the specific needs of the drug development project. Initially, a high-throughput screening of conditions is performed to identify potential solid forms. This is followed by a detailed characterization of the identified forms to determine their stability, manufacturability, and suitability for further development. The CDMO combines expert knowledge with advanced analytical capabilities to guide clients towards the best solid form for their drug substance.
Yes, solid state screening can significantly influence drug patent strategy. Identifying and patenting unique solid forms, such as polymorphs, salts, or co-crystals, can provide additional intellectual property protection and potentially extend the patent life of a drug. This strategy can offer competitive advantages and create barriers to entry for generic formulations, highlighting the importance of thorough solid state screening in the drug development and commercialization process.
Polymorphs are different crystalline forms of the same molecular compound, which can exhibit varying physical and chemical properties. Salts are formed when the drug substance reacts with a counterion, potentially improving solubility or stability. Co-crystals consist of the drug substance and one or more unique co-former molecules in a single crystalline structure, which can alter the drug's physical properties without changing its chemical identity. Each of these solid forms can offer distinct advantages in terms of bioavailability, stability, and processability.
Solid state screening plays a crucial role in formulation development by identifying the solid form that offers the best combination of stability, solubility, and manufacturability. The selected solid form can influence the choice of excipients, the design of the manufacturing process, and the formulation strategy for achieving the desired drug release profile. This ensures that the final dosage form meets the therapeutic goals and regulatory requirements.
Challenges in solid state screening include the identification and characterization of metastable forms, managing polymorphic transformations during processing, and predicting the solubility and bioavailability of different solid forms. Additionally, the complexity of co-crystal formation and the selection of appropriate conditions for salt formation can pose significant challenges. A CDMO must leverage extensive expertise and advanced analytical technologies to navigate these challenges effectively.
A CDMO ensures quality and compliance in solid state screening by adhering to Good Laboratory Practices (GLP) and following rigorous standard operating procedures (SOPs) for all analytical methodologies. Quality control measures include regular calibration of analytical instruments, validation of analytical methods, and thorough documentation of all screening activities and results. Compliance with regulatory guidelines and industry best practices ensures the reliability and reproducibility of the screening outcomes.
Clients can engage with a CDMO for solid state screening services by initiating a consultation to discuss their project needs and objectives. The CDMO will typically conduct a feasibility assessment, propose a customized screening plan, and provide a detailed proposal outlining the scope of work, timelines, and costs. Throughout the project, the CDMO maintains open communication with the client, providing regular updates and comprehensive reports on the screening outcomes and recommendations for further development.