Benoxaprofen, polymorphs

T. Yokoyama, N. Ohnishi, T. Umeda, T. Kuroda, Y. Kita, K. Kuroda, and Y. Matsuda, Kinetic study on the isothermal transition of benoxaprofen polymorphs in the solid state at high temperature, Chem. Pharm. Bull. 34, 917-921 (1986). 

Other studies have demonstrated that polymorph differences do not always translate into bioavailability differences. Gunning et al. (1976) have published results fordisopyramide, an example of a drug that showed similardissolution rates for both forms (I and II). Bioavailability studies in healthy human volunteers also showed no differences in bioavailability from identical capsule formulations of the two polymorphs. Umeda et al. (1984) reported on the case of benoxaprofen, in which the two forms had no signiLcant differences in bioavailability in rabbits, despite a 1.5 times solubility advantage for form I over form II. Bioavailability differences for solid states need to be veriLed by in vivo studies, and in those cases where there is no advantage, the more stable form should bi developed for stability reasons. 

SR Byrn, G Gray, RR Pfeiffer, J Frye. Analysis of solid-state carbon-13 NMR spectra of polymorphs (benoxaprofen and nabilone) and pseudopolymorphs (cefaz-olin). J Pharm Sci 74 565-568, 1985. 

The polymorphic transition of carbamazepine from form I to form III and that of benoxaprofen from form I to form II exhibited m values of 2.23 and 2.24, respectively, indicating possible mechanisms involving two-dimensional growth of nuclei.61 1578 When m is approximately equal to 2, the reaction conforms to the Avrami-Erofe evequation ... 

The data for carbamazeine and benoxaprofen plotted according to Eq. (3.3) are shown in Figs. 143 and 144, respectively and the rate constants k obtained from the slopes gave linear Arrhenius plots, indicating that it might be possible to predict the polymorphic transition rates at other temperatures (Fig. 145). 

Figure 144. Polymorphic transition kinetics of benoxaprofen from form I to form II according to the Avrami-Erofe ev equation (Eq. 3.3). (Reproduced from Ref. 578 with permission.)...

Different polymorphic forms of solid benoxaprofen, nabilione and pseudopolymoiphic (i.e. including solvent) crystal forms of cefazolin were analyzed in 1985 by Bym et al. [33]. Solid state C NMR spectra of ciystal forms I and II of benoxaprofen were recorded a spectrum of the pharmaceutical granulation exhibited the signals of excipients but was identical to that of form II. The spectra of nabilone I and II allowed for a determination of which polymorph is present in a binary mixture. Hydrated crystal forms of cefazolin, the sesquihydrate, pentahydrate and monohydrate, gave different signal positions the amorphous form can be distinguished from crystalline ones because it showed broadened resonances. 

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