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    Development of HPLC Methods for Individual Determination of 20 Active Pharmaceutical Ingredients for Ussing-Chamber Studies
    (Bentham Science Publ Ltd, 2017) Kaynak, Mustafa Sinan; Akgeyik, Emrah; Ates, Muge; Celebier, Mustafa; Sahin, Selma
    Background: The aim of this study was to develop HPLC methods for individual determination of 20 active pharmaceutical ingredients (amoxicillin sodium, antipyrine, atenolol, caffeine, carbamazepine, cimetidine, enalapril, furosemide, hydrochlorothiazide, ibuprofen, ketoprofen, metoprolol tartrate, methyldopa, naproxen sodium, pindolol, piroxicam, propranolol HCl, ranitidine, theophylline, and verapamil HCl) to be used for determination of their intestinal permeabilities across Ussing-Chamber. Method: Two different stationary phases (Waters X-Bridge C18-150 x 4.6 mm, 5 mu m; and ACE 5 C18- 150 x 4.6 mm, 5 mu m) were used for the separation of the compounds. Three different aqueous phases (20 mM phosphate buffers pH 3.0, pH 6.0 and water) and two different organic phases (methanol and acetonitrile) were used to prepare the mobile phases. Total analysis time was shorter than 7 minutes for all applications. Result: The developed methods were validated according to the ICII guideline and found to be linear, sensitive, selective, precise and accurate. The developed methods could be applied for analyses of these compounds not only for Ussing-Chamber studies but also for other permeability studies.
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    Effect of permeability enhancers on paracellular permeability of acyclovir
    (Wiley, 2016) Ates, Muge; Kaynak, Mustafa Sinan; Sahin, Selma
    Objectives According to Biopharmaceutics Classification System (BCS), acyclovir is a class III (high solubility, low permeability) compound, and it is transported through paracellular route by passive diffusion. The aim of this study was to investigate the effect of various pharmaceutical excipients on the intestinal permeability of acyclovir. Methods The single-pass in-situ intestinal perfusion (SPIP) method was used to estimate the permeability values of acyclovir and metoprolol across different intestinal segments (jejunum, ileum and colon). Permeability coefficient (P-eff) of acyclovir was determined in the absence and presence of a permeation enhancer such as dimethyl beta-cyclodextrin (DM-beta-CD), sodium lauryl sulfate (SLS), sodium caprate (Cap-Na) and chitosan chloride. Key findings All enhancers increased the permeability of paracellularly transported acyclovir. Although Cap-Na has the highest permeability-enhancing effect in all segments, permeation-enhancing effect of chitosan and SLS was only significant in ileum. On the other hand, DM-beta-CD slightly decreased the permeability in all intestinal segments. Conclusions These findings have potential implication concerning the enhancement of absorption of paracellularly transported compounds with limited oral bioavailability. In the case of acyclovir, Cap-Na either alone or in combination with SLS or chitosan has the potential to improve its absorption and bioavailability and has yet to be explored.
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    Multi-Segmental Evaluation of Intestinal Permeability of Amlodipine at Two Dose Levels
    (Bentham Science Publ Ltd, 2025) Ates, Muge; Stelmasinska, Agata Bogacz; Stelmasinska, Michal; Barre, Liban; Buyuktuncel, Ebru; Kaynak, Mustafa Sinan; Sahin, Selma
    Background Intestinal permeability plays a crucial role in drug absorption, as it varies across different gastrointestinal regions, affecting the bioavailability of orally administered drugs. This variability, combined with dose-dependent absorption, influences the overall efficacy and pharmacokinetics of the drug.Objective This study aimed to investigate the impact of three intestinal regions (jejunum, ileum, and colon) along with two different doses of amlodipine (AML) (5 mg and 10 mg) on its permeability.Methods An optimized HPLC method was developed and validated for the simultaneous quantification of AML, metoprolol (MTP), and phenol red (PR), while a modified single-pass intestinal perfusion (SPIP) was used to assess AML permeability across different intestinal segments.Results Net Water Flux (NWF) showed significant fluctuations, with high positive values in the colon, indicating distinct physiological responses in this region. The effective permeability (Peff) of AML varied across different intestinal segments and doses. In the jejunum and ileum, the Peff of AML decreased with increasing doses from 5 mg to 10 mg, while in the colon, Peff remained relatively stable. Peff values ranged from 3.50 x 10-4 cm/s for the 5 mg dose to 1.80 x 10-4 cm/s for the 10 mg dose in the jejunum, from 3.30 x 10-4 cm/s (5 mg) to 2.41 x 10-4 cm/s (10 mg) in the ileum, and from 6.65 x 10-4 cm/s (5 mg) to 6.79 x 10-4 cm/s (10 mg) in the colon.Conclusion This study demonstrated significant segmental and dose-dependent variations in the intestinal permeability of AML using the SPIP model in rats.