Semipermeable containers

Marketed Drug Product Packaged in Semipermeable Containers ... 

Aqueous-based products packaged in semipermeable containers should be evaluated for potential water loss in addition to physical, chemical, biological, and microbiological stability. This evaluation can be carried out under conditions of low RH, as discussed below. Ultimately, it should be demonstrated that aqueous-based drug products stored in semipermeable containers can withstand low-RH environments (Table 2.5). Other comparable approaches can be developed and reported for nonaqueous, solvent-based products. 

A 5% loss in water from its initial value is considered a significant change for a product packaged in a semipermeable container after an equivalent of 3 months of storage at 40°C and not more than (NMT) 25% RH. However, for small containers (1 mL or less) or unit-dose products, a water loss of 5% or more after an equivalent of 3 months of storage at 40°C and NMT 25% RH may be appropriate if justified. 

If the drug product is packaged in a semipermeable container, appropriate information should be provided to assess the extent of water loss. Data from refrigerated storage should be assessed according to details given below (Table 2.7). 

For liquid (e.g., solution, suspension, elixir) and semisolid (e.g., creams, ointments) dosage forms in permeable or semipermeable container closure systems, a change to an ink and/or adhesive used on the permeable or semipermeable packaging component to one that has never been used in a CDER-approved product of the same dosage form, same route of administration, and same type of permeable or semipermeable packaging component (e.g., low density polyethylene, polyvinyl chloride). 

The high relative humidity conditions cited in Table 4 apply to APIs and solid dosage forms. Low relative humidity conditions should be used for liquid drug products in semipermeable container-closure systems. The ICH Draft Revised Stability Guidance suggests low RH conditions of 40%+ 5% relative humidity for long-term studies, 60%+ 5% relative humidity for intermediate studies, and not more than 25% RH accelerated studies. 

Semipermeable containers Containers that allow the passage of solvent, usually water, while preventing solute loss. The mechanism for solvent transport occurs by absorption into one container surface, diffusion through the bulk of the container material, and desorption from the other surface. Transport is driven by a partial pressure gradient. Examples of semipermeable containers include plastic bags and semirigid, low-density polyethylene (LDPE) pouches for large volume parenteral (LVPs), and LDPE ampoules, bottles, and vials. 

For liquid (e.g., solution, suspension, elixir) and semisolid (e.g., creams, ointments) dosage forms in permeable or semipermeable container closure systems, a change to an ink or adhesive... 

For sterile water for injection and LVP solutions of inorganic salts packaged in semipermeable containers (e.g., plastic bags), the following statement may be used on the immediate container labels ... 

LVP solutions packaged in a semipermeable container (e.g., aplastic bag) and containing simple organic salts (e.g., acetate, citrate, gluconate, and lactate, and dextrose 10%... 

Estimation of Osmotic Pressure.—(i) Direct.— The solution of known concentration is enclosed in a semipermeable container attached to a manometer tube. The container is immersed in a vessel containing an excess of the solvent, some of which diffuses into the container causing a rise of the solution in the manometer tube. When equilibrium is reached, the osmotic pressure of the diluted solution inside the container is balanced by the hydrostatic pressure of the liquid in the manometer, and can be measured in atmospheric units. Modifications of the apparatus include the use of a mercury manometer to avoid excessive dilution of the mixture, and the employment of metallic containers with frames to support the membranes. 

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