In Situ Fiber-Optic Dissolution Assisted by a Mathematical Separation Model of Dynamic Three-Wavelength K-Ratio Spectrophotometry

The aim of this study was to monitor the drug release of ibuprofen sustained-release capsules in real time in situ. A mathematical separation model of dynamic three-wavelength K-ratio spectrophotometry was established to eliminate the interference of gelatin capsule shells when drug release was monitored by a fiber-optic drug dissolution in situ test system. A control experiment with high performance liquid chromatography was performed simultaneously. Within 7 h, real-time drug release profiles were obtained. The average drug release rates were 19.79%, 37.34%, 63.13%, and 88.41% by the fiber-optic drug dissolution in situ test system at the respective time points of 1 h, 2 h, 4 h, and 7 h. There were no significant differences between the in situ and control methods. Drug release of ibuprofen sustained-release capsules can be monitored by the fiber-optic drug dissolution in situ test system assisted by the mathematical separation model of dynamic three-wavelength K-ratio spectrophotometry. Information about the entire dissolution process can be produced by the real-time release profile. INTRODUCTION The determination of the release rate of active ingredients from drug formulations is an important procedure in pharmaceutical research. Without automation, it is a labor-intensive process. The fiber-optic sensor based on ultraviolet–visible (UV–vis) absorption analysis for dissolution testing is a technique that has been under investigation for many years (1–3). Drug dissolution process analysis with fiber-optics uses a fiber-optic probe inserted directly into each vessel, and the absorbance of the solution is measured in situ instead of extracting samples and determining the concentration of active ingredient with UV spectrophotometry or high performance liquid chromatography (HPLC). This approach is rapid and efficient, with less handling of the samples and consequently fewer sources of error. A pharmaceutical tablet, however, always contains a number of other compounds (i.e., excipients), and sometimes these compounds can influence the determination of the active ingredient. When samples from the dissolution test are analyzed without any separation, excipients that have absorbance at the same wavelength as the drug may have a large influence on the dissolution data. Scattering can be generated from undissolved particles and excipients, which can contribute significant interference. This type of scattering may be either wavelength-independent or wavelength-dependent. Both of the two interferences can be eliminated by some algorithm (4). The use of fiber optics, an automatic controlling system, and software, together with powerful chemometric data evaluation, can open up new possibilities for a deeper understanding of in vitro dissolution testing (5). In 1988 a partial-least-squares (PLS) statistical method was used to correct for the disturbance caused by solution turbidity in dissolution testing (1). In 2000 a fiber-optic sensor system was utilized by Chen et al. (6) for on-line dissolution monitoring of multicomponent solid preparations containing vitamins B1, B2, and B6. In addition, in 2008 it was reported that thirty-five excipient samples and five placebos were selected to evaluate the Delphian fiber-optic dissolution system in the wavelength range of 200–400 nm (3). Fenbid (Ibuprofen Sustained-Release Capsules), a product of GlaxoSmithKline (Sino-American Tianjin SmithKline and French Lab., Ltd), is an ibuprofen pain reliever featuring a 12-h sustained-release formula. The absorbance of the gelatin capsule shells at 264 nm can interfere with the measurements of ibuprofen, which has a maximum absorbance at about 264 nm. The vessels were sampled at 1, 2, 4, and 7 h, then determined by HPLC according to the Chinese Pharmacopeia 2005 (Ch.P) (7). In this paper, a mathematical separation model of dynamic three-wavelength F-ratio spectrophotometry, which can eliminate the interference of gelatin capsule shells, was investigated. The drug release of ibuprofen *Corresponding author. diss-17-02-03.indd 15 2010-6-2 15:06:28 dx.doi.org/10.14227/DT170210P15