Complex dosage forms

Complex dosage forms, such as modified-release products, transder-mal patches, metered-dose inhalers... 

In contrast to solution-phase or direct polarization solid-state NMR experiments, CP-MAS is not a truly quantitative technique. As a result of the cross-polarization step, the integral intensities of peaks in CP-MAS spectra do not directly reflect the stoichiometry of nuclei in the molecule. CP-MAS signals originate from protons, and its transfer efficiency varies from carbon to carbon, based on proximity of protons and local mobility of the molecule. In most pharmaceutical applications, only relative concentrations of mixtures of two or more polymorphs need to be determined even in complex dosage forms. The absolute concentration of the drug in formulation is usually known or can be determined by other techniques. 

Long-term stability studies (available data at the time of original filing and subsequent amendments) The expiration dating period for complex dosage forms will be determined on the basis of available long-term stability data submitted in the application... 

For complex dosage forms as described in the previous section, a reduced number of site-specific batches may be justified if accelerated and long-term data are available at the time of application submission on batches made at a different pilot or commercial site from the intended commercial facility. 

Some radiopharmaceuticals are rather complex dosage forms. Radiolabelled nanospheres, nanoparticles, nanocolloids, peptides, monoclonal antibodies and glass particles for radioembolisation are a few examples. Also autologous blood cells can be radiolabelled, outside or inside the body. The radiolabelling of blood cells is used in routine practice. 

Most controlled release dosage forms administer dmg according to thek design, whether conceptually simple, eg, a fixed release rate for a fixed amount of time, or complex, eg, several different rates for different amounts of time. Alternatively, closed-loop systems contain a sensor to monitor dmg concentration or to administer dmg according to a biological need (11). 

Fractional Order. In the decomposition of pure solids, the kinetics of reactions can often be more complex than simple zero- or first-order processes. Carstensen [88] has reviewed the stability of solids and solid dosage forms as well as the equations that can be used in these cases. In addition to zero- and first-order kinetics, solid-state degradations are often described by fractional-order equations. 

The number of the constituent phases of a disperse system can be higher than two. Many commercial multiphase pharmaceutical products cannot be categorized easily and should be classified as complex disperse systems. Examples include various types of multiple emulsions and suspensions in which solid particles are dispersed within an emulsion base. These complexities influence the physicochemical properties of the system, which, in turn, determine the overall characteristics of the dosage forms with which the formulators are concerned. 

Animal drug dosage forms can be as complex and sophisticated as drugs used in humans, if not more so. 

Since dosage forms contain more than just active drug, it is of practical interest to understand how the various components from a multicomponent solid influence their own dissolution and release. Nelson [18] was one of the first pharma-ceuticists to ponder this question and perform the initial dissolution studies. Unfortunately, Nelson initially considered the dissolution of interacting solids (benzoic acid + trisodium phosphate), which is a more complicated and more complex situation than simple multicomponent dissolution of noninteracting solids. Nelson did show that for his benzoic acid and trisodium phosphate pellets, there was a maximum increase in benzoic acid dissolution in water at a mole fraction ratio of 2 1 (benzoic acid trisodium phosphate) and that the benzoic acid dissolution rate associated with the maximum rate was some 40 times greater than that of benzoic acid alone. 

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