Dissolution characteristics

Contact with steel, though less harmful, may accelerate attack on aluminium, but in some natural waters and other special cases aluminium can be protected at the expense of ferrous materials. Stainless steels may increase attack on aluminium, notably in sea-water or marine atmospheres, but the high electrical resistance of the two surface oxide films minimises bimetallic effects in less aggressive environments. Titanium appears to behave in a similar manner to steel. Aluminium-zinc alloys are used as sacrificial anodes for steel structures, usually with trace additions of tin, indium or mercury to enhance dissolution characteristics and render the operating potential more electronegative. 

Table 1 In Vitro Dissolution Characteristics of Two Commercial Phenytoin Sodium Capsule... 

The product specification should include a measure of uniformity of content and a dissolution test following the release of the active ingredient until steady state is achieved (or justifying shorter periods of testing). Where possible, the dissolution specification (often expressed as quantity of active ingredient released per unit area of surface per unit time) should be related to the results obtained from batches found to be acceptable in clinical studies. In these tests six units should be tested for dissolution characteristics and the mean value stated with a measure of variability. 

This chapter describes some of the properties of solids that affect transport across phases and membranes, with an emphasis on biological membranes. Four aspects are addressed. They include a comparison of crystalline and amorphous forms of the drug, transitions between phases, polymorphism, and hydration. With respect to transport, the major effect of each of these properties is on the apparent solubility, which then affects dissolution and consequently transport. There is often an opposite effect on the stability of the material. Generally, highly crystalline substances are more stable but have lower free energy, solubility, and dissolution characteristics than less crystalline substances. In some situations, this lower solubility and consequent dissolution rate will result in reduced bioavailability. 

Calcium carbonate0 Turns 500, 750, 1,000, 1,250 Increase or decrease by 500 0.5-1 g (elemental calcium) three First-line agent dissolution characteristics and phosphate binding... 

In order to determine the appropriate development conditions, we examined dissolution characteristics for resist films in the aqueous alkaline developers by measuring film thickness as a function of development time. In Figure 7, dissolution characteristics for the new resist before and after exposure to KrF excimer laser are compared with those for the styrene resin matrix. 

Dissolution characteristics of solid dosage forms, which depend on formulation in addition to the properties of the chemical itself (e.g., vehicle may decrease permeability of suspension or capsule to water and retard dissolution and diffusion). 

In summary, the model proposed on the basis of acid-base characteristics of kaolinite platelets explains the pH-dependent charge primarily to the protonation of the hydroxyl groups at the basal gibbsite and the edge surface. We will later illustrate how this charge characteristics (surface protonation) influences the reactivity (dissolution characteristics) of kaolinite. 

The same test conditions used for the pure drug powder can now be used to compare formulations. The dissolution characteristics of potassium phenoxymethylpenicillin and several IR formulations of this drug that are available on the German market were compared, along with the dissolution of the pure drug powder (Fig. 2) at both low and almost neutral pH. The results show that dissolution is formulation-dependent. For the formulations tested, dissolution from some was virtually... 

Figure 2 Dissolution characteristics of potassium phenoxymethyl-penicillin pure drug and several formulations available on the German market according to the test conditions given in Table 3 (A) At acid pH (the pH used to generate the data shown here was pH 1.2 rather than pH 2 as indicated in the Table) and (B) at pH 6.8.

For IR dosage forms of highly soluble drugs, it is likely to be difficult to produce batches with widely enough varying dissolution characteristics to be able to establish an IVIVC (see Chapter 10). This is because of the need to have side-batches whose dissolution and absorption rates vary by at least 10% (each side of) the batch of interest, typically the pivotal batch or the marketed product. 

The first step is to assess the solubility and dissolution characteristics of the pure drug in biorelevant media which cover the usual pH range in the GI tract. Some useful compositions are shown in Table 4. 

Figure 7 Behavior of two formulations of a poorly soluble, weakly basic drug (solubility characteristics shown in Figure 6) in media composed at two pHs—one to represent acidic conditions in the stomach, the other to represent the hypochlorhydric stomach. (A) Formulation with non-robust dissolution characteristics and (B) Formulation with robust dissolution characteristics.

If not in an ER product, a drug is likely to exhibit dissolution-limited absorption if it is poorly soluble in the GI lumen. Usually, identification of a compound with dissolution-limited GI absorption is based on D S ratio (4) when D S is about < 250 mL over the pH range of 1-7.5, the compound is usually considered to have less than ideal lumenal dissolution characteristics (3,5), with 250 mL being a conservative estimate of the total volume of fluids that will be in contact with the dose in the upper GI tract under fasting conditions. However, this approach has several weaknesses ... 

The method for the evaluation of similarity of dissolution profiles depends on dissolution characteristic of the reference and test drug product. If both formulations (average value of n = 12 each) dissolve at least 85% of label claim within 15 min, dissolution profiles are generally assumed as similar and no further testing or data analysis is required. 

Some of the physicochemical properties of the active pharmaceutical ingredient (API) that influence the dissolution characteristics are ... 

The dissolution characteristics of oral formulations should be evaluated over the physiologic pH range of 1.2-6.8 [1.2-7.5 for modified release (MR) formulations]. During method development, it may be useful to measure the pH before and after a run to see if the pH changes during the test,... 

Certificate of analysis giving date of manufacture, batch number, weight of material and range, dissolution characteristics, appearance excipients expiry data and assurance of compliance with good manufacturing practice... 

Westerhoff et al. (23) studied the dissolution characteristics of several SJW products under biorelevant conditions. Components of SJW have a broad spectrum of polarity and solubility, and representative compounds from each group were examined. Although labelling indicates that several... 

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