Dissolution rate piroxicam

Table 6 Apparent Permeability and Dissolution Rates for Piroxicam Capsules...

The combined effect of pH and surfactants on the dissolution of piroxicam has been reported. " In this system, the dissolution rate and solubility of the drug substance could be well estimated by a simple additive model for the effect of pH and surfactant, where the total dissolved concentration equaled the summation of the amoimt of dissolved non-ionized substance, the amount of dissolved ionized substance, and the amoimt of substance solubilized in the surfactant micelles. It was suggested that the model developed in this work could be useful in establishing an in vitro-in vivo correlation for piroxicam. 

This effect of particle size on dissolution rate of sparingly soluble drug substances has been demonstrated in many instances by the superior dissolution rates observed after size reduction. Examples of compounds studied in such work include methylprednisolone (Higuchi et al., 1963), l-isopropyl-7-methyl-4-phenylquinazolin-2(lH)-one (Kornblum and Hirschorn, 1970), griseofulvin (Ullah and Cadawader, 1971), monophenylbutazone (Habib and Attia, 1985), nitrofurantoin (Eyjolfsson, 1999), and piroxicam (Swanepoel et al., 2000). 

There are numerous examples of medicinal products in which dissolution rate enhancing technologies are applied to increase the bioavailabiUty or absorption rate of an active substance. Cardiac glycosides should be given as micronised particles in a solid oral dosage form because otherwise their dissolution rate and hence their bioavaUability is too low. Piroxicam was shown to be absorbed faster when given as a cyclodextrin complex, which increases the dissolution rate. Similarly, the bioavailabiUty of albendazole as a cyclodextrin complex was increased compared to crystalline non-complexed albendazole, based on the same mechanism. And finally, the bioavailabiUty of amorphous chloramphenicol is higher than that of crystalline chloramphenicol. 

There are abundant examples in the literature that demonstrate the direct relationship between dissolution rate and bioavailability. One such example is that of piroxicam (Figure 7.6), a potent non-steroidal anti-inflammatory drug that was launched in 1981 by Pfizer for multiple conditions such as arthritis (osteoarthritis and rheumatoid arthritis) and spondylitis. It is a zwitterionic drug (p ai = 1S6 and p a2 = 5.46) and is classified as a low solubility and high permeability drug (i.e., class II) based on the Biopharmaceutics Classification System (BCS). In an attempt to improve its bioavailability after oral administration, the authors prepared three different ethanolamine salt forms i.e., mono-, di- and triethanolamine salts). These salt forms were selected based on prior literature precedence where they enhanced the percutaneous absorption of piroxicam.PK studies of the ethanolamine salts revealed that both the exposure (AUC) and the C ax of piroxicam in plasma followed the same trend as the dissolution profile at pH 6.8, which varied in the order mono- > di- > tri-piroxicam. The monoethanolamine salt showed the highest exposure with the relative bioavailability increasing almost 1.9-fold, while the di- and tri- salts were 1.7 times better than piroxicam. The C ax values showed 2.14-, 1.6- and... 

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