Oral Solutions and Suspensions Manufacturing

Oral Solutions and Suspensions Manufacturing

• Oral solutions and suspensions present unique manufacturing challenges compared to other dosage forms.
• Bioequivalency concerns are minimal except in cases where dissolution is a critical factor (e.g., phenytoin suspension).
• Recalls of liquid products often stem from microbiological, potency, and stability issues.
• Liquid dosage forms are used by vulnerable populations (neonates, pediatrics, geriatrics) who might have compromised drug metabolism or other clearance issues.
• Inadequate dosage forms can pose significant risks due to altered absorption profiles.

Facilities Design

• Facility design depends on the product type and potential for cross-contamination.
• Isolation might be necessary for certain sensitive products (e.g., steroids).
• Processes creating dust need isolation.
• HVAC systems need validation, comparable to potent drug processes.
• Proper validation, including stress testing, is essential to prevent potential breakdowns, potentially preventing greater costs.
• Cross-contamination concerns are reduced once the active ingredient is in solution form.
• Pressure differentials help prevent contamination from other powder sources.

Equipment Considerations

• Equipment should be of sanitary design (sanitary pumps, valves, flow meters).
• Ball valves, pump packing, and flow meter pockets are potential contamination sources.
• Equipment sourced from less developed countries may have different sanitary standards.
• Manufacturers should insist on sanitary certification.
• Manufacturing and filling lines need meticulous documentation in drawings and standard operating procedures (SOPs).
• Minimal cross-contamination between manufacturing areas and filling areas by utilizing short delivery lines and thorough SOPs.

Batching and Mixing

• Batching is typically based on weight, not volume.
• Weighing systems (load cells) provide greater accuracy in solution/suspension volume calculation compared to volumetric measurements.
• Volumetric measurements (dipsticks, tank lines) should be validated.
• Manufacturers check bulk solution/suspension samples before filling.
• Weight-based batching produces less variable results compared to volume-based batching.

Batching Tank Design

• Bottom discharge valves should be flush with the tank floor.
• Valves several inches/a foot below the tank bottom may create "dead legs," potentially trapping drug or preservatives and impacting potency.
• Suspensions require flush-mounted valves.

Transfer Lines

• Hard-piped transfer lines are easy to clean and sanitize.
• Flexible hoses are a potential contamination source.
• Proper storage methods (allowing hoses to drain) are important to prevent moisture-related contamination.
• Manifolds (common connections) in water, premix, or raw material supplies, can be significant contamination sites.

Raw Materials

• Drug particle size, especially for suspensions, is crucial.
• Micronized drug particles are used in topical and suspension formulations.