Abstract
Purpose: To develop a simple and rapid reversed-phase high performance liquid chromatographic (HPLC) method with UV detection for the simultaneous determination of diclofenac, metoprolol tartrate, phenol red and propyl paraben in intestinal segments.Methods: The mobile phase consisted of 55 % methanol, 45 % of 12.5 mM potassium dihydrogen phosphate (KH2PO4) aqueous solution, adjusted to pH 7.0 using 0.2 N sodium hydroxide (NaOH) solution, and to which 0.3 % (v/v) triethylamine was added. Analysis was run at a flow rate of 1.0 mL/min with a 12 min total run time at ambient temperature. The developed method was successfully applied to determination of the analytes in samples obtained from in situ single pass intestinal perfuson (SPIP) studies.Results: The calibration curves were linear for all compounds (r > 0.999) with a limit of detection (LOD) of 0.005, 0.1, 0.075 μg/mL, and limit of quantification of 0.1, 0.3, 0.2 μg/mL for metoprolol tartrate, phenol red and diclofenac respectively. The coefficient of variation for intra-day and inter-day precision was < 5 % and accuracy was between 98 and 102 %. Based on SPIP and HPLC studies, the estimated mean permeability in jejunum, ileum and colon was 0.319 ± 0.184, 0.639 ± 0.241 and 0.84 3± 0.517 x 10-4 cm/sec, respectively, for metoprolol tartrate while the corresponding permeability values were 1.585 ± 0.729, 1.154 ± 0.433 and 1.775 ± 1.576 x 10-4 cm/sec for diclofenac.Conclusion: The findings indicate that diclofenac is a highly permeable compound and its absorptionoccurs throughout the intestinal tract. Furthermore, the developed method is suitable for the analysis of diclofenac and metoprolol in intestinal regions.Keywords: Biopharmaceutics classification system, Diclofenac, Metoprolol tartrate, Segmental permeability, Intestinal absorption, Validation
Highlights
Absorption of orally administered drugs could vary at different segment of the small intestine such as duodenum, jejunum, and ileum [1,2]
The retention time of diclofenac decreased with decreasing KH2PO4 concentration, the concentration of KH2PO4 in the mobile phase was fixed at 0.0125 M (Figure 1)
There is no results available in the literature for colonic permeability of metoprolol tartrate, our jejunal and ileal permeability values were very similar to the literature values of 0.20 - 0.59 x 10-4 cm/sec [2,13,19]
Summary
Absorption of orally administered drugs could vary at different segment of the small intestine such as duodenum, jejunum, and ileum [1,2]. Since the small intestinal transit of drug formulations is about 3 4 h, significant part of the dose of drug in a modified release product can possibly reach the colon. This means that the absorption of the drug which is used for modified release formulations has to be classified as high permeability in the entire intestine. It is important to understand the absorption characteristics in the entire intestinal tract for BCS class II and III drugs, in order to identify and develop strategies for modifiedrelease formulations [4]. For enteric coated diclofenac sodium tablets, drug is released once the tablet reaches the duodenum, with subsequent rapid absorption [7]
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