Stability testing suspensions

The most important parameters for the physical stability of suspensions are the relative volume of sediment (= volume of sediment/total volume) and the redispersability. They are tested after 1 -4 weeks have elapsed. 

Lazaric, K. Cucek, B. Faust, G. RPTLC method for determining parabins in oral antacid suspension during stability testing. J. Planar Chromatogr.-Mod. TLC 1999,12, 86-88. 

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. 

This is a useful guide to the physical stability of suspensions. If freeze—thaw cycling or elevated temperature exposures are chosen for physical stability testing, companion samples of a closely related marketed suspension should be included in the testing protocol for comparison purpose because pharmaceutical suspensions are not normally designed to withstand temperature extremes during storage (15-30°C optimum). 

One complication which arises when we are carrying out stability testing of suspensions is the changes in the solubility of the suspended drug with increase in temperature. With suspensions, the concentration of the drug in solution usually remains constant because, as the decomposition reaction proceeds, more of the dmg dissolves to keep the solution saturated. As we have seen, this situation usually leads to zero-order release kinetics. If the acmal decomposition of dissolved dmg is first-order, then we can express the decrease of concentration, c, with time, t, as... 

In order to prepare a suspension of polynucleotides or nucleic acids in a solvent (e.g., in glycerol) we have used a low-power, short-time (5-10 min) ultrasonihcation method, and although the ultrasonihcation could, in principle, have lead to complete disintegration of the sample, we found that these compounds remained stable and intact under our operating conditions. Stability tests do not show detectable modifications in either base structure or composition. 

Compared to emulsions and foams discussed earlier, assessment of the stability of suspensions is relatively straightforward in most cases. Bottle or centrifuge tests are commonly used. Samples of the suspension components, and the suspension stabilizer or destabilizer to be tested, if any, are mixed in bottles or centrifuge tubes in a specified way, then let stand or centrifuged at a specified -force level. After a defined period of time, the suspensions are examined. For this, a timescale appropriate to the process under consideration has to be set. 

Among single drug component studies, usual vehicles for dilution are 5% dextrose (D5W), 0.9% sodium chloride (normal saline, NS), aqueous buffers, peritoneal dialysis fluid, nonaqueous solvents, water for injection, phosphate-buffered saline, bacteriostatic water for injection, bacteriostatic sodium chloride. Ringer s injection, and lactated Ringer s. Stability studies can also be carried out on the drug product solution as such or in specific containers or injection devices. Solutions and suspensions can also be prepared extemporaneously and stability tested to show worthiness for oral, ophthalmic, or rectal administration. The following is an example of the first... 

Some studies with filled and unfilled rigid PVC were made in our laboratory to describe the effect of chalk as additional stabilizer. A suspension PVC (K-value 70) with an organotin stabilizer (2 phr) and lubricants (1.8 phr) was used as the experimental material. A part of this compound was filled with a stearic acid coated calcium carbonate (10 phr) as an additional component. The PVC powder and the additives were mixed at a high speed in an intensive mixer. The received dry blends were pelletized by extrusion to get a better dispersion of the additives in the polymer material. Finally, the granulates were processed by injection molding to test specimens for measurements of mechanical properties. 

The above rheological parameters can be used to assessment and predict the long-term physical stability of suspension concentrates. They offer valuable tools to the formulation chemist for the development of stable systems. In addition, one can design a simple rheological technique for evaluation of the suspension concentrate during manufacture (quality assurance test). 

Stndies of the antoxidation of carotenoids in liposomal suspensions have also been performed since liposomes can mimic the environment of carotenoids in vivo. Kim et al. stndied the antoxidation of lycopene," P-carotene," and phytofluene" " in liposomal snspensions and identified oxidative cleavage compounds. Stabilities to oxidation at room temperature of various carotenoids incorporated in pig liver microsomes have also been studied." The model took into account membrane dynamics. After 3 hr of reactions, P-carotene and lycopene had completely degraded, whereas xanthophylls tested were shown to be more stable. 

The purpose of in-use stability studies is to establish the period for which a product intended to be used on more than one occasion may be used after reconstitution or dilution or the withdrawal of the first dose from the container without adversely affecting the integrity of the product and with the product retaining acceptable quality characteristics. This type of test can be applied to any multiple use product (e.g., sterile products in multiple-use containers, powders or granules including those used to produce oral solutions or suspensions) but is likely to be of particular importance in the case of products that are manufactured with an inert headspace gas, for products containing antioxidants to protect an active ingredient that is liable to oxidative decomposition, and for products that contain a volatile antimicrobial preservative. 

Experimental measurements in each lake included particle concentration and size measurements in the water column, sedimentation fluxes in sediment traps, and chemical and size characteristics of materials recovered from sediment traps. The colloidal stability of the particles in the lake waters was determined with laboratory coagulation tests. Colloidal stability was described by the stability ratio (a). For a perfectly stable suspension, a = 0 for a complete unstable one, a = 1.)... 

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