Dissolution methods

From the discussion above, it is clear that a dissolution test is much more discriminatory than disintegration is assessing potential in vivo performance of various solid dosage forms. 

A number of academic, government and industrial scientists have developed dissolution rate tests that have been used to evaluate the in vitro dissolution rate of a drug from a dosage form and, hopefully, to correlate it with in vivo drug availability. All these methods measure the rate of appearance of dissolved drug in an aqueous fluid (similar to GI fluid) under carefully controlled conditions temperature, agitation, and pH. 

Two official methods given in the United States Pharmacopeia and recognized by US Food and Dmg Administration (FDA) and, hence, used by the pharmaceutical industry are  

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Los Alamos is processing a wide variety of residues, including Pu-Be neutron sources, polystyrene-Pu02-U02 blocks, incinerator ash, Pu-U alloys and oxides, Pu-Zr alloys and oxides, Pu-Np alloys and oxides, Pu-Th alloys and oxides, etc. Processes have been developed for these scrap items (see Figure 2), but we need to know more about Pu-Np separations Pu-Th separations oxalate precipitations for both plus 3 and plus 4 valences valence stabilization dissolution methods for high-fired impure oxides in-line alpha monitors to measure extremely low concentrations of Pu and Am in HNO3 solutions and solubility of various mixtures of Pu02 and UO2 under a variety of conditions. 

The advantage of the direct dissolution method is its simplicity. Systems that form vesicles under this method are easily dissolved in aqueous solution, unlike many other systems that form irregular aggregates due to strong hydrophobic interactions. Also, since the aqueous environment is relatively mild, this method... 

The present photoelectrochemical deposition/dissolution method is applicable to reversible control of the particle size. A typical application taking advantage of the method is the multicolor photochromism. Additional applications include surface patterning and photoelectrochemical actuator. The patterning is possible by using a thiol-modified silver... 

For the purpose of the identification and quantification of additives (broadly defined) in polymeric materials extraction and dissolution methods are favoured (Sections 3.3-3.7). However, additives are also made accessible analytically by digestion of the sample matrix (cf. Section 8.2). Such wet chemical techniques, that remove the sample matrix first, are often limited to mg amounts because of pressure build-up in destruction vessels. Another reactive extraction approach to facilitate additive analysis is depolymerisation by acid hydrolysis or saponification, sometimes under pressure. This is then frequently followed by chemical methods such as titrimetry or photometry for final identification and quantification. 

Principles and Characteristics Extraction or dissolution methods are usually followed by a separation technique prior to subsequent analysis or detection. While coupling of a sample preparation and a chromatographic separation technique is well established (Section 7.1), hyphenation to spectroscopic analysis is more novel and limited. By elimination of the chromatographic column from the sequence precol-umn-column-postcolumn, essentially a chemical sensor remains which ensures short total analysis times (1-2 min). Examples are headspace analysis via a sampling valve or direct injection of vapours into a mass spectrometer (TD-MS see also Section 6.4). In... 

Table 9.2 Main features of dissolution methods for poly-mer/additive deformulation...

Isolation may occur by liquid-solid interaction (extraction, dissolution) or heat (thermal, pyrolytic, laser). Extraction methods easily handle qualitative screening for low- to medium-MW compounds fail for high-MW components or polymer-bound functionalities and are less reliable quantitatively (analyte dependent). When applicable, dissolution methods suffer from sensitivity, because of the dilution effect on account of the polymer. In-polymer analysis performs well for qualitative screening, but is as yet not strongly performing for quantitative analysis, except for some specific questions. 

Table 10.32 is a shortlist of the characteristics of the ideal polymer/additive analysis technique. It is hoped that the ideal method of the future will be a reliable, cost-effective, qualitative and quantitative, in-polymer additive analysis technique. It may be useful to briefly compare the two general approaches to additive analysis, namely conventional and in-polymer methods. The classical methods range from inexpensive to expensive in terms of equipment they are well established and subject to continuous evolution and their strengths and deficiencies are well documented. We stressed the hyphenated methods for qualitative analysis and the dissolution methods for quantitative analysis. Lattimer and Harris [130] concluded in 1989 that there was no clear advantage for direct analysis (of rubbers) over extract analysis. Despite many instrumental advances in the last decade, this conclusion still largely holds true today. Direct analysis is experimentally somewhat faster and easier, but tends to require greater interpretative difficulties. Direct analysis avoids such common extraction difficulties as ... 

LM Mortada, FA Ismail, SA Khalil. Correlation of urinary excretion with in vitro dissolution using four dissolution methods for ampicillin capsules. Drug Dev Ind Pharm 11 101-130, 1985. 

The basic assumption behind the sequential dissolution methods is that a particular extractant is phase or retention mode specific in its chemical attachment on a mixture of forms (D Amore et al., 2005). The procedure... 

The wide variety of methods for determining the dissolution rates of solids may be categorized either as batch methods (Fig. 13A) or as continuous-flow methods (Fig. 13B). The common batch-type dissolution methods are derived from the beaker-stirrer method of Levy and Hayes [89] and include a number of thoroughly standardized procedures, especially those defined by the U.S. Pharmacopoeia [90]. 

The dissolution rate of a solid may be defined as dm/dt, where m is the mass of solid dissolved at time t. In a batch dissolution method, the analyzed concentration, cb, in the solution (if well stirred) is representative of the entire volume, V, of the dissolution medium, so that... 

While batch dissolution methods are simple to set up and to operate, are widely used, and may be carefully and reproducibly standardized, they suffer from the following disadvantages (1) the hydrodynamics are usually poorly characterized, with the notable exception of the rotating disc method, (2) a small change in dissolution rate will often create an undetectable and therefore an immeasurable perturbation in the dissolution time curve, and (3) the solute concentration cb may not be uniform throughout the solution volume V. 

Continuous-flow (i.e., column dissolution) methods, depicted schematically in Fig. 13B, have limited, but growing, application [92-94]. The volume flow rate, dVIdt, of the dissolution medium must remain constant to achieve the steady state shown in Fig. 14B, so that... 

Ninhydrin, 22 101 Ninhydrin-color reaction amino acids, 2 570 Niobates, 27 152-153 24 315 Niobia-phosphate catalytic aerogels, 2 763t Niobic acid, 27 152 Niobic salts, 27 152-153 Niobium (Nb), 27.132-157 24 313, 315. See also Nb-Ti entries Niobium compounds Niobium metal analytical methods for, 27 142-144 dissolution methods for, 27 142 economic aspects of, 27 140-142 effect on stainless steel corrosion resistance, 7 809... 

One popular method of separating an analyte species from a complicated liquid sample is the technique known as liquid-liquid extraction or solvent extraction, first mentioned in Chapter 2. In this method, the sample containing the analyte is a liquid solution, typically a water solution, that also contains other solutes. The need for the separation usually arises from the fact that the other solutes, or perhaps the original solvent, interfere in some way with the analysis technique chosen. An example is a water sample that is being analyzed for a pesticide residue. The water may not be a desirable solvent and there may be other solutes that may interfere. It is a selective dissolution method—a method in which the analyte is removed from the original solvent and subsequently dissolved in a different solvent (extracted) while most of the remainder of the sample remains unextracted, i.e., remains behind in the original solution. 

The USP 27, NF22 (11) now recognizes seven dissolution apparatus specifically, and describes them and, in some cases allowable modifications, in detail. The choice of the dissolution apparatus should be considered during the development of the dissolution methods, since it can affect the results and the duration of the test. The type of dosage form under investigation is the primary consideration in apparatus selection. 

A. When developing a dissolution method, the design qualification is built into the apparatus selection process. The dosage form and delivery system process will dictate at least initially the equipment of choice. For example, the first choice for a beaded product may be United States Pharmacopeia (USP) Apparatus 3, which is designed to confine the beads in a screened-in cylinder. 

Rohrs BR. Dissolution method development for poorly soluble compounds. Dissolution Technol 2001 8(3) 6—12. 

Leeson LJ. ANDA dissolution method development and validation. Dissolution Technol 1997 4(1) 5—9, 18. 

The 2002 BP has 73 capsule monographs with dissolution applied for 29. In the same edition, 351 tablet monographs can be found with 103 of them giving a dissolution method (17). 

Needham TE, Shah K, Kotzan J, Zia H. Correlation of aspirin excretion with parameters from different dissolution methods. J Pharm Sci 1978 67 1070-1073. 

Joergensen K, Jacobsen L. Factorial design used for ruggedness testing of flow through cell dissolution method by means of Weibull transformed drug release profiles. Inti J Pharm 1992 88 23-29. 

Dissolution Method Development with a View to Quality Control... 

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