Injectable Lyophilized Dosage Form

Pre-formulation is the foundational phase that characterizes the physicochemical properties of the drug substance to guide formulation strategies. Key activities include:

• Solubility and pKa Determination: Assessing aqueous solubility and pKa to inform buffer selection and salt formation.
• Melting Point and Polymorphism Studies: Identifying melting points and polymorphic forms to predict stability and crystallization behavior.
• Thermal Analysis: Using Differential Scanning Calorimetry (DSC) to determine glass transition and collapse temperatures, which are crucial for lyophilization cycle design.
• Excipient Compatibility: Evaluating interactions between the active pharmaceutical ingredient (API) and excipients to prevent instability.

This phase focuses on creating a stable, effective, and manufacturable lyophilized product. Key considerations include:

• Lyophilization Cycle Optimization: Designing freezing and drying conditions to achieve desired cake appearance, reconstitution time, and moisture content.
• Buffer and Excipient Selection: Choosing stabilizers, bulking agents, and tonicity modifiers to enhance stability and solubility.
• Formulation Screening: Conducting stability studies under various conditions to identify optimal formulations.
• Scale-Up Studies: Translating laboratory formulations to pilot and commercial scales while maintaining product quality.

Analytical method development:

Creating robust methods to accurately measure drug concentration, purity, and stability.

Analytical method validation:

Ensuring methods meet regulatory standards for accuracy, precision, and reliability.

Analytical Method Transfer:

Transferring validated methods across sites to maintain consistency and support scale-up and compliance.

Effective technology transfer ensures consistent product quality across different manufacturing sites. Steps include:

• Process Documentation: Providing detailed protocols and specifications.
• Training: Educating receiving sites on processes and quality standards.
• Scale-Up Validation: Conducting trials to confirm that scaled processes yield consistent product quality.

Core Equipment for Lyophilized Injectable Formulation

Lyophilizer Martin Christ Lyophilizer

Freeze-Dry Microscopy LYOSTAT 4.0

Test Parameter

• Identification
• Assay
• Solvent Content
• Water Content
• Related Substances
• Reconstitution Time & Volume
• pH of Reconstituted Solution
• Osmolality of Reconstituted Solution
• Color and Clarity
• Content Uniformity (UOD)
• Particulate Matter
• Bacterial Endotoxin Test (BET)
• Sterility
• Residual solvents
• Elemental impurities

Key Instruments

• HPLC & UPLC’s-UV, PDA, RI, CAD (Make: Agilent / Water’s)
• Particle Size Analyser (Make: Malvern; Model: Sizer 3000)
• Particle Size Analyser (Make:Malvern; Model:Zeta sizer Nano ZSP)
• Polarized Light Microscope (Make: Axio Lab 5; ZEN software)
• Viscometer (Make: Brookfield; Model: DV Next; RV; CP)
• pH meter (Orion Star A211/Thermo)
• UVVisible spectrophotometer [Shimadzu, UV-2600]
• Gas chromatography (Make: Agilent; Model: 8890)
• Osmometer (K-7400S, Knauer GmbH)
• Stability chambers including Photostability chamber [Thermolab Make]
• Volumetric and Coulometric KF Auto titrator [Metrohm make]
• FT-IR (Make: Shimadzu)
• Dissolution apparatus (Electrolab; Trust-E14, Trust E-08, with iDisso)