Suspensions chemical stability

Profiles of pH versus solubility and pH versus stability are needed for solution and suspension formulations to help assure physical and chemical stability as well as to maximize or minimize solubility. This information is also valuable for predicting the compatibility of drugs with various infusion fluids. 

Parker, R.J. et al. (2005) Stability and comparative metabolism of selected felbamate metabolites and postulated fluorofelbamate metabolites by post-mitochondrial suspensions. Chemical Research in Toxicology, 18 (12), 1842-1848. 

For nebulizer and other aqueous aerosol products that use suspension systems, excipients are used to influence particle physical and chemical stability (e.g., microcrystalline cellulose for nasal sprays). The suitability of the physicochemical properties of these critical excipients should be thoroughly investigated and documented (12). Far more excipients have been included in formulations designed for nasal administration (Table 4). 

It is important to characterize the physicochemical properties of the suspensions well, so that the PK data can be interpreted appropriately. Typical characterization of the drug substance includes purity, residual solvents, aqueous solubility pro Lie (pH 2, FaSSIF), crystallinity (XRPD/DSC), particle size, pl and logP. For solution formulations at various stages of discovery studies, dose analysis is essential, and for efLcacy assessment and toxicology studies, chemical stability for the... 

For instance, when the chemical stability of a suspension of ibuprofen powder and other ibuprofen-wax microspheres was studied with a modified HPLC procedure for three months, the amount of drug released from the microspheres was affected by the medium pH, type of suspending agent, and storage temperature without observing chemical degradation of the drug [49]. 

A different important issue in this context is the chemical stability of ceramic suspensions, which is indispensable for inkjet printing. For chemical stability, either steric or by charge, the surface to mass ratio is important S/m = 3/ pR). Due to the high density p of ceramics, a stable suspension also requires that the particles not be too large, i.e., be smaller than about 2 m. 

Variations in assay results can be avoided by the preparation of homogeneous, well-mixed, or non-settling fine particle suspensions (size 1-10 pm). Particle size reduction results in slow, more uniform settling rates. The bioavailability of drugs is improved by reducing the size of suspension particles. Furthermore, drug particles smaller than 20 pm produce less pain and tissue irritation when injected parenterally. However, fine particles may have a deleterious effect on chemical stability because of their high dissolution rate. 

Chemical stability predictions are sometimes complicated by the difficulty of determining the pH value of suspensions, which often changes because of surface coating of electrodes and differences between bulk-suspension and supernatant-vehicle readings. Accelerated elevated temperature stability testing often has a pronounced adverse effect on viscosity, particle solubility, and size distribution. 

Adjustments in pH lo maintain water solubility cun sometimes lead lo chemical stability problems. An example is indomelhacin (HA acid pK ,4.S). which is unstable in alkaline media. Therefore. Ihc preferred oral liquid dosage form is a suspension buffered at pH 4 to 5. Because this is near the drug s pK . only. W f will be in the water-soluble form. There is a medical indication requiring intravenous administration of indomelhacin to premature infants. The intravenous dosage form is the lyophilized (freeze-dried) sodium salt, which is reconstituted just prior lo use. 

Titanium dioxide (Ti02) has been the most commonly applied photocatalyst because of its chemical stability and low toxicity. The decomposition of organic contaminants in Ti02 suspensions is initiated by photogenerated electron/hole pairs as follows ... 

Oral liquids would typically be aqueous, nonaqueous, or blends to create a solution. In some cases they may be a suspension if it is difficult to find a vehicle that completely solubilizes the active or yields chemical stability. The liquid may be used directly as is from the container or, if sold in a concentrated form, is diluted before administration. Oral... 

Insoluble salts may be prepared using high molecular weight counterions to reduce the solubility of the drug for formulation of a suspension, to improve chemical stability, provide improvements in solid-state stability, reduce acid lability and permit formulation of tasteless or controlled release products. Erythromycin stearate, which is poorly soluble in acidic media (an enteric salt), is less prone to decomposition in gastric fluids than the more acid-soluble free base. 

An essential property required to obtain a physically stable suspension formulation is that the drag substance has a low solubility in the suspension vehicle. This applies to all types of suspension whether intended for oral, parenteral or inhalation delivery. Since most suspensions are aqueous, a low solubility in water is required to prevent drug dissolution and crystal growth on storage. Some drugs intended for intramuscular use are formulated as suspensions in oil (e.g. penicillin injections are formulated in sesame oil) to improve chemical stability via a reduction in solubility. 

One of the most successful cation exchange resins, because of its chemical stability, is cross-linked polystyrene. It is obtained by polymerization of a suspension of styrene in water, together with a cross-linking... 

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