Injectable Suspension Dosage Form

Injectable suspension formulations are complex systems with a solid phase dispersed in a liquid, designed for subcutaneous or intramuscular administration and requiring careful development. The following sections outline key considerations for developing injectable suspensions.

Pre-formulation Studies

Essential to characterize the active pharmaceutical ingredient (API) and its interactions with potential excipients. Key aspects include:

• Solubility and Stability: Evaluate API across pH levels to guide buffer and stabilizer selection.
• Injection Vehicle: Select low-viscosity vehicles with good wetting properties to ensure injectability.
• Excipient Selection: Use suitable stabilizers, viscosity enhancers, and preservatives to support formulation performance.

Prototype Development and Manufacturing Process Development

During prototype formulation development, several factors must be considered:

• Buffer and pH Selection: Using acetate or phosphate buffers to control pH, maintaining stability and minimizing irritation.
• Compatibility with Container Closure Systems: Evaluating formulation-packaging interactions to prevent leaching or degradation.
• The manufacturing process for injectable suspensions involves several critical steps:
• Sterile Manufacturing Environment: Producing in Class 100 or better environments to ensure sterility.
• Scale-Up Considerations: Optimizing process parameters during scale-up to maintain product quality.

Stability studies

• Prototype Stability studies as per ICH conditions: Conducting long-term studies under ICH conditions to monitor appearance, potency, and quality.
• Freeze thaw and Thermal cycling studies: Simulating extreme conditions to assess impact during transport.
• Photo-stability studies: Generating data on light sensitivity to determine photostability of API or finished product.

Equipment available at R&D:

High Shear Homogenization IKA T25 Digital Ultra Turrax

High Pressure Homogenization PANDA Plus 2000, GEA

Particle Size Analyzer Make & Model: Nikon E600 Microscope with NIS Elements

Particle size Analyzer (Micro Range) Make: Malvern; Model: Sizer 3000

Particle size Analyzer (Nano Range) Make: Malvern; Model: Zeta sizer Nano ZS

• Analytical method development:
  Developing robust methods for accurate testing of concentration, purity, and stability.
• Analytical method validation:
  Validating methods to ensure accuracy, precision, and regulatory compliance.
• Analytical Method Transfer:
  Transferring validated methods across sites to maintain consistency and data integrity.

Test Parameters

• Description
• Identification
• Assay
• Antioxidant content
• Preservative content
• Related substances
• pH
• Osmolality
• In-vitro drug release (dissolution)
• Color and Clarity
• Content Uniformity (UOD)
• Particulate matter
• Bacterial Endotoxin Test (BET)
• Sterility
• Anti-Microbial Effectiveness Testing (AET)
• Container closure integrity test
• Container content
• Viscosity
• Residual solvents
• Elemental impurities
• Extractable and Leachable
• Particle Size distribution (PSD) & Zeta Potential

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).
• UV-Visible spectrophotometer [Shimadzu, UV-2600]
• Gas chromatography (Make: Agilent; Model: 8890)
• Osmometer (K-7400S, Knauer GmbH)
• Dissolution apparatus (Electrolab; Trust-E14, Trust E-08, with iDisso)
• Stability chambers including Photostability chamber [Thermolab Make]
• Volumetric and Coulometric KF Auto titrator [Metrohm make]
• FT-IR (Make: Shimadzu)