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ABSTRACT Acheflan® herbal medicine is the first medicine developed and produced in Brazil using Cordia verbenacea DC., Boraginaceae, essential oil as a constituent. C. verbenacea has anti-inflammatory properties, which have been directly related to α-humulene and trans-caryophyllene. Currently, the quantification of α-humulene and trans-caryophyllene in C. verbenacea has only been described by GC-MS. Although this technique is widely used it cannot be directly applied to finished medicinal products since they contain aqueous constituents. In this context, the objective of this work was to develop a methodology for quantifying C. verbenacea in raw materials and in pharmaceutical formulations using liquid chromatography. The Box-Behnken experimental design was used successfully to optimize the analytical method. The method developed in this study was validated and proven to be effective in the proper separation of α-humulene and trans-caryophyllene. In addition, the developed method was applied to commercial formulations (cream and aerosol) containing C. verbenacea essential oil, which resulted in very satisfactory separation without interference from excipients. C. verbenacea oil contains four times higher concentrations of trans-caryophyllene than α-humulene. Therefore, we propose that trans-caryophyllene can be used as a marker of C. verbenacea essential oil. Evaluation of trans-caryophyllene content would be especially valuable for applications where the concentrations are very low such as in permeation and release studies of dermatological formulations.
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Aims: Develop an anti-tuberculosis (TB) Fixed Dose Combination (FDC) tablet containing an immediate release layer (IRL) composed of both rifampicin (RIF) and pyrazinamide (PYR) and a retarded release layer (RRL) comprised of isoniazid (INH) which would allow segregated delivery of RIF and INH. Study Design: Trials were conducted on the pre-formulations and formulations to assess the compatibility of excipients and obtain a modified release profile, for an IRL consisting of both RIF and PYR and a RRL containing INH. Place and Duration of Study: This study was performed at the Laboratory of Pharmaceutical Industrial Technology, Drug and Pharmaceutical Department, Faculty of Pharmacy, between March 2008 and April 2010. Methodology: Preformulation studies were performed on RIF and PYR, alone and in combination with excipients. The pharmacopeic attributes of the distinct layers and the FDC tablets were evaluated for hardness, friability and disintegration time. The FDC bilayer tablets were analyzed for their drug content and cumulative dissolution of the drug. Results: Fourier transform infrared, x-ray diffraction and differential scanning calorimetry results revealed the presence of amorphous and crystalline RIF forms and no potentially relevant incompatibilities were identified in the kneaded system containing RIF, PYR and excipients. In vitro drug release from the FDC tablets revealed that the intragranular addition of croscarmellose sodium into the IRL rendered a cumulative dissolution of RIF and PYR within the limits of simulated gastric fluid. And, for RRL, the most effective retardant matrix excipient was found to be hydroxypropyl methylcellulose. Conclusion: Segregated delivery of RIF and INH from bilayer tablets is an option for the development of immediate release FDC tablets and the retarded release of INH, this strategy proved suitable for preventing contact of these two drugs under acidic conditions. This finding suggested that RIF had a high in vivo bioavailability which qualifies this FDC for future bioavailability studies.
RESUMO
In this study, two methods, based on high-performance liquid chromatography (HPLC) and UV spectrophotometry, were developed and validated for the quantitative determination of lumiracoxib in tablets. The HPLC was carried out on a column of propylsulfonic acid bonded to silica gel (250 x 4.6 mm; 5 mium), with a mobile phase of phosphate buffer (pH 7.4; 10 mM)-water-acetonitrile (10:40:50, v/v/v) fl owing at 1.0 mL/min and detection of the drug at 278 nm. The UV method was based on absorbance at 275 nm, with ethanol as solvent. Both assays were linear over the concentration range of 230 miug/mL (R approximate 0.999), as wellas accurate and precise, with recoveries between 98 and 100% and relative standard deviation (%RSD) smaller that 2.0%. The proposed methods are highly sensitive, precise and accurate and were successfully applied to the quantitation of lumiracoxib in the commercial formulation. The spectrophotometric method is a simple, cheap and less time-consuming method. However, the chromatographic method is selective for the determination of the degradation products of lumiracoxib.