Dissolution method characteristics

TABLE 3 Dissolution Method Characteristics and Their Relative Importance in Drug Development... 

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 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 ... 

The first step in the preparation of Pt-group metals is the dissolution of the raw materials (primary deposits, ores, metal scraps, supported catalysts, etc.). According to the characteristics of their content in the different mixed noble metals, different dissolution methods are used. Typical processes are dissolution in... 

The validation requirements are discussed as they apply to both the sample preparation and sample analysis aspects of a dissolution method. The focus of the discussion in this chapter is on the validation considerations that are unique to a dissolution method. Validation is the assessment of the performance of a defined test method. The result of any successful validation exercise is a comprehensive set of data that will support the suitability of the test method for its intended use. To this end, execution of a validation exercise without a clearly defined plan can lead to many difficulties, including an incomplete or flawed set of validation data. Planning for the validation exercise must include the following determination of what performance characteristics to assess (i.e., strategy), how to assess each characteristic (i.e., experimental), and what minimum standard of performance is expected (i.e., criteria). The preparation of a validation protocol is highly recommended to clearly define the experiments and associated criteria. Validation of a test method must include experiments to assess both the sample preparation (i.e., sample dissolution) and the sample analysis. ICH Q2A [1] provides guidance for the validation characteristics of the dissolution test and is summarized in Table 4.1. 

Dissolution. Dissolution testing of dipyridamole tablets is to be performed according to the directives of General Method (711), with the inclusion of the following method characteristics ... 

A serious drawback that can arise with the one-step dissolution method is the possible partial occlusion of the active metal in the bulk of the support leading to a loss of metallic surface available for the catalytic reaction. Cases in which that problem occurred have been mentioned in Section 8.2.2.1. devoted to the two-steps method which represents a possible alternative to avoid occlusion. However, because of the above mentioned advantages of the one-step methods, it is really worth to try to solve the problem of metal occlusion by improving the one-step methods. In the following Section, a second one-step method that allows to avoid occlusion and leads to unique structural characteristics is presented. 

Our formulation development activities we developed both a biorelevant dissolution method, and a drug product release method. At this point in development, all of our formulation development activities are complete, making the biorelevant method less important. The formulation(s) is fixed, and we are now concerned with demonstrating that we can consistently manufacture batches of drug product. We will also want to show that the release characteristics of the dosage unit do not change on stability. Oiu" drug product release method will fulfill this role and will be the primary dissolution method, until the method conditions need to be revisited when in vivo data become available from om first clinical studies. At that time, the method should be revisited to evaluate how biorelevant our in vitro data are. 

Abstract This chapter explores the manner in which the surface analysis methods of X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) can be used to extract information regarding the interfacial chemistry of adhesion from polymer/metal systems such as adhesive joints. It will be shown that the analysis of a failure interface is an uncertain method to extracting interface chemistry but in certain situations, where a very thin layer of polymer remains on the metal oxide surface, this provides spectra characteristic of the interphase. In most situations, some form of chemical or mechanical sectioning is necessary, and microtomy and dissolution methods are described as ways in which chemical information at high depth resolution can be extracted from the interphase zone. 

The formation of such materials may be monitored by several techniques. One of the most useful methods is and C-nmr spectroscopy where stable complexes in solution may give rise to characteristic shifts of signals relative to the uncomplexed species (43). Solution nmr spectroscopy has also been used to detect the presence of soHd inclusion compound (after dissolution) and to determine composition (host guest ratio) of the material. Infrared spectroscopy (126) and combustion analysis are further methods to study inclusion formation. For general screening purposes of soHd inclusion stmctures, the x-ray powder diffraction method is suitable (123). However, if detailed stmctures are requited, the single crystal x-ray diffraction method (127) has to be used. 

Solution Deposition of Thin Films. Chemical methods of preparation may also be used for the fabrication of ceramic thin films (qv). MetaHo-organic precursors, notably metal alkoxides (see Alkoxides, metal) and metal carboxylates, are most frequently used for film preparation by sol-gel or metallo-organic decomposition (MOD) solution deposition processes (see Sol-GEL technology). These methods involve dissolution of the precursors in a mutual solvent control of solution characteristics such as viscosity and concentration, film deposition by spin-casting or dip-coating, and heat treatment to remove volatile organic species and induce crystaHhation of the as-deposited amorphous film into the desired stmcture. 

Dissolution of 5 could be enhanced in H2O by solid dispersion systems with urea and mannitol (97MI27). A method for solubilizing 5 and 6 at near physiological pH was patented (98EUP856316). Solubility characteristics of 5 was investigated in an in vitro tear model (98MI24). 

Table 3.51 Main characteristics of dissolution/precipitation methods...

From the characteristics of the methods, it would appear that FD-MS can profitably be applied to poly-mer/additive dissolutions (without precipitation of the polymer or separation of the additive components). The FD approach was considered to be too difficult and fraught with inherent complications to be of routine use in the characterisation of anionic surfactants. The technique does, however, have a niche application in the area of nonpolar compound classes such as hydrocarbons and lubricants, compounds which are difficult to study using other mass-spectrometry ionisation techniques. 

Application to solid polymer/additive formulations is restricted, for obvious reasons. SS-ETV-ICP-MS (cup-in-tube) has been used for the simultaneous determination of four elements (Co, Mn, P and Ti) with very different furnace characteristics in mg-size PET samples [413]. The results were compared to ICP-AES (after sample dissolution) and XRF. Table 8.66 shows the very good agreement between the various analytical approaches. The advantage of directly introducing the solid sample in an ETV device is also clearly shown by the fact that the detection limit is even better than that reported for ICP-HRMS. The technique also enables speciation of Sb in PET, and the determination of various sulfur species in aramide fibres. ETV offers some advantages over the well-established specific sulfur analysers very low sample consumption the possibility of using an aqueous standard for calibration and the flexibility to carry out the determination of other analytes. The method cannot be considered as very economic. 

Principles and Characteristics Of the chromatographic methods discussed in Chapter 4 essentially only SEC and HPLC are used to some extent for the analysis of dissolutions containing both macromolecular and additive components. SPE is a useful device for working... 

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