Suspensions drug, physical stability

Physical Stability of Drug Suspension. The physical stability of the non-polar drug suspensions formulated in pMDIs again depends on many parameters, such as propellant type, chemical properties of the drug compounds, and the surfactants used in the formulation. A suspension is a liquid system in which insoluble solid particles are dispersed in a liquid medium. Suspensions can be divided into colloidal suspensions, in which the... 

There are some useful methods to improve the physical stability of a suspension, such as decreasing the salt concentration, addition of additives to regulate the osmolarity, as well as changes in excipient concentrations, unit operations in the process, origin and synthesis of the drug substance, polymorphic behavior of the drug substance crystals, and other particle characteristics. However, methods based on changes of the particle properties and the surfactants used are the most successful [43],... 

When added to a suspension, benzoic acid dissociates, with the benzoate anion adsorbing onto the suspended drug particles. This adsorption alters the charge at the surface of the particles, which may in turn affect the physical stability of the suspension. ... 

Physical stability is assessed by placing samples of the elastic liposome suspension into vials that are flushed with nitrogen and sealed. The vials are stored under varied conditions such as light protected or exposed, refrigerated and at room temperature. At different time periods (e.g. 10, 20, 30 days and monthly up to 6 months) the samples are analysed for particle size and residual drug content. 

If the drug is insufficiently soluble to allow delivery of the required dose as a solution (the maximum delivered dose for each nostril is 200 p,L), then a suspension formulation will be required. There are additional issues for suspension products, for example crystal growth, physical stability, resuspension, homogeneity and dose uniformity. Suspension products will also require information on density, particle size distribution, particle morphology, solvates and hydrates, polymorphs, amorphous forms, moisture and/or residual solvent content and microbial quality (sterile filtration of the bulk liquid during manufacture is not feasible). 

B. Solid Suspension If the amorphous drug is dispersed in the polymer matrix at the particle level, it is referred to as an amorphous solid suspension, distinguished by two separate Tg values of the drug and the polymer. The physical stability relies on immobilization and isolation of the amorphous particles in a rigid polymer matrix. 

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