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Publisher: Peytchinski Publishing
ISSN: 1312-773X (Online)
Issue: 2018, vol. 24, issue4
Subject Area: Medicine
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DOI: 10.5272/jimab.2018244.2303
Published online: 17 December 2018
Original article
J of IMAB. 2018 Oct-Dec;24(4):2303-2312
KINETIC MODELING ON AMIDE HYDROLYSIS, DRUG RELEASE AND MUCOSAL PERMEATION OF INDOMETHACIN IN THE COMPOSITION OF SELECTED SEMISOLID VEHICLES
Nadezhda A. Ivanova1
, Tsvetelina S. Stefanova2, Ivelin R. Iliev2, Georgi S. Stoyanov3, 4, Kameliya Zh. Bratoeva5,
1) Department of Pharmaceutical Technologies, Faculty of Pharmacy, Medical University, Varna, Bulgaria
2) Students at Faculty of Pharmacy, Medical University, Varna, Bulgaria
3) Department of General and Clinical Pathology, Forensic Medicine and Deontology, Faculty of Medicine, Medical University, Varna, Bulgaria
4) Department of Anatomy and Cell Biology, Faculty of Medicine, Medical University, Varna, Bulgaria
5) Department of Physiology and Pathophysiology, Division of Pathophysiology, Faculty of Medicine, Medical University, Varna, Bulgaria.
ABSTRACT:
The present study aims to reveal the role of a semi-solid vehicle in the composition of Indomethacin dosage forms for their physical and chemical stability, in vitro and ex vivo behavior. Three types of hydrogels and emulgels were prepared with gelling agents Methylcellulose 2%, Poloxamer 407 20% and Carbomer 940 1%. Each preparation was observed for physical and chemical stability at 5°C and 25°C within 3 months. Test formulations, along with USP standard Indomethacin gel and combined marked product Indextol,were subjected to in vitro drug release test and ex vivo permeation study, using porcine intestinal mucosa on Franz diffusion cell. A hypothesis was built to predict steady-state plasma concentration (Css) of Indomethacin for each formulation following mucosal administration. Results revealed sustained chemical stability of all emulgels for the period observed and significantly lower chemical stability of the corresponding hydrogels. Methylcellulose hydrogel (at both temperatures) and emulgel (at 25°C) showed signs of phase separation, while all other formulations kept their physical appearance for the duration of the study. Methylcellulose emulgel along with Poloxamer 407 hydrogel showed highest cumulative drug release in 12 hours (58.01% and 55.00%, respectively). Same formulations exhibited also highest drug permeation rate (Jss) through mucosa (10.55 µg.cm-2.h-1 and 13.20 µg.cm-2.h-1, respectively) and highest predicted value of plasma concentration (Css up to 100.49 µg.l-1 and 125.71 µg.l-1, respectively), whereas highest drug deposition in mucosal tissue was detected for Poloxamer 407 emulgel (2.1 mg.cm-3).
Keywords: herbal medicines, menopause, alternative therapy,
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Please cite this article as: Ivanova NA, Stefanova TS, Iliev IR, Stoyanov GS, Bratoeva KZ. Kinetic modeling on amide hydrolysis, drug release and mucosal permeation of Indomethacin in the composition of selected semisolid vehicles. J of IMAB. 2018 Oct-Dec;24(4):2303-2312.
DOI: 10.5272/jimab.2018244.2303
Correspondence to: Nadezhda A. Ivanova, Department of Pharmaceutical Technologies, Faculty of Pharmacy, Medical University – Varna; 84, Tsar Osvoboditel str., Varna, Bulgaria; E-mail: nadejda__iv@abv.bg
REFERENCES:
1. Vranic E, Uzunovic A. Dissolution studies of physical mixtures of indomethacin with alpha- and gamma-cyclodextrins. Bosn J Basic Med Sci.2010 Aug;10(3):197-203. [PubMed] [Crossref]
2. El-Leithy ES, Ibrahim HK, Sorour RM. In vitro and in vivo evaluation of Indomethacin nanoemulsion as a transdermal delivery system. Drug Deliv. 2015 Nov;22(8):1010-1017. [PubMed] [Crossref]
3. Czajkowska-Kosnik A, Sznitowska M. Solubility of ocular therapeutic agents in self-emulsifying oils. I. Self-emulsifying oils for ocular drug delivery: solubility of indomethacin, aciclovir, and hydrocortisone. Acta Pol Pharm. 2009 Nov-Dec;66(6):709-13. [PubMed]
4. Karasulu HY, Şanal ZE, Sözer S, Güneri T, Ertan G. Permeation Studies of Indomethacin from Different Emulsions for Nasal Delivery and Their Possible Anti-Inflammatory Effects. AAPS Pharm Sci Tech. 2008; 9(2):342-8. [PubMed] [Crossref]
5. Dadwal M, Mittal P, Ranal S. Formulation Development And Evaluation Of Indomethacin Emulgel. IJPRD. 2014 Jan;5(11):081-88.
6. Mulye SP, Wadkar KA, Kondawar MS. Formulation development and evaluation of Indomethacin emulgel. Der Pharmacia Sinica. 2013; 4(5):31-45.
7. Kusuma R, Samba Siva Rao A. Formulation, Development, and Evaluation of Indomethacin Emulgel Using Pregelatinized Starch from Ipomoea batata Tubers. Asian J Pharm. 2015 Oct-Dec;9(4):43-50.
8. Krzek J, Starek M. Simultaneous Densitometric Determination of Indomethacin and Its Degradation Products, 4-Chlorobenzoic Acid and 5-Methoxy-2-Methyl-3-Indoleacetic Acidin Pharmaceutical Preparations.J. AOAC Int. 2001 Nov-Dec;84 (6):1703-07. [PubMed]
9. Kougioumtzoglou A, Peikova L, Georgieva M, Zlatkov A. Evaluation of the Stability of Indomethacin Substance Under a Model of Physiological Conditions Using Modified and Validated RP-HPLC Method. Pharmavia. 2015; 62 (2):10-17.
10. Temussi F, Cermola F, Dellagreca M, Iesce MR, Passananti M, Previtera L, et al. Determination of photostability and photodegradation products of indomethacin in aqueous media. J Pharm Biomed Anal. 2011 Dec;56(4):678–83. [PubMed] [Crossref]
11. El-Badry M, Fetih G, Fathy M. Improvement of solubility and dissolution rate of indomethacin by solid dispersions in Gelucire 50/13 and PEG4000. Saudi Pharm J. 2009 Jul;17(3): 217-25. [PubMed] [Crossref]
12. Comer J, Judge S, Matthews D, Towes L, Falcone B, Goodman J, et al. The intrinsic aqueous solubility of indomethacin. ADMET DMPK. 2014 Apr;2(1):18-32. [Crossref]
13. Saeedi M, Akbaria J, Morteza-Semnanib K, Enayati-Farda R, Sar-Reshteh-dara S, Soleymania A. Enhancement of Dissolution Rate of Indomethacin Using Liquisolid Compacts. Iran J Pharm Res. 2011 Winter;10 (1):25-34. [PubMed]
14. Casas M, Ferrero C, Jiménez-Castellanos Mª R. Graft tapioca starch copolymers as novel excipients for controlled-release matrix tablets. Carbohydr Polym. 2010 Mar;80(1):71-77. [Crossref]
15. Singhvi G, Singh M. Review: In-Vitro Drug Release Characterization Models. Int J Pharm Sci Res. 2011 Jan- Mar;2(1):77-84.
16. Cojocaru V, Ranetti A L, Hinescu L G, Ionescu M, Cosmescu C, Po’toarcг AG, et al. Formulation And Evaluation Of In Vitro Release Kinetics Of NA3CADTPA Decorporation Agent Embedded In Microemulsion-Based Gel Formulation For Topical Delivery. Farmacia. 2015 Sep-Oct;63(5):656-664.
17. Amores S, Domenech J, Colom H, Calpena A, Clares B, Gimeno A, et al. An improved cryopreservation method for porcine buccal mucosa in ex vivo drug permeation studies using Franz diffusion cells. Eur J Pharm Sci. 2014 Aug 18;60:49-54. [PubMed] [Crossref]
18. Brodin B, Steffansen B, Nielsen C. Passive diffusion of drug substances: the concepts of flux and permeability, Molecular biopharmaceuticals. Pharmaceutical Press. 2009. Chapter 3.2, p. 135-52.
19. Khan S, Gajbhiye C, Singhavi DJ, Yeole P. In situ Gel of Metoprolol Tartrate: Physicochemical Characterization, In vitro Diffusion and Histological Studies. Indian J Pharm Sci. 2012 Nov-Dec;74(6):564-70. [PubMed] [Crossref]
20. Herkenne C, Naik A, Kalia Y, Hadgraft J, Guy R. Ibuprofen Transport into and through Skin from Topical Formulations: In Vitro –In Vivo Comparison. J Investig Dermatol. 2007 Jan;127(1):135-42.[PubMed] [Crossref]
21. Vankov V, Ovcharov VL. [Anatomy of the human body]. Arso Sofia. 2016. [inBulgarian]
22. Helleberg L. Clinical Pharmacokinetics of Indomethacin. Clin Pharmacokinet. 1981 Jul-Aug;6(4):245-58. [PubMed] [Crossref]
23. Alvan G, Orme M, Bertilsson L, Ekstrand R, Palmér L. Pharmacokinetics of indomethacin. Clin Pharmacol Ther. 1975 Sep;18(3):364-73. [PubMed]
24. Shah A, Khan A, Usman M, Qureshl R , Siddiq M, Shah S. Thermodynamic Characterization Of Dexamethasone Sodium Phosphate And Its Complex With Dna As Studied By Conductometric And Spectroscopic Techniques. J Chil Chem Soc. 2009 Jun;54(2):134-137. [Crossref]
25. Dzegilenko NB, Vtorova ZE, Korchagin VB. [Quantitative determination of anhydroleandomycin and glycol in oleandomycin phosphate]. Antibiotiki. 1976 Apr;21(4):313-6. [in Russian] [PubMed].
Received: 25 June 2018
Published online: 17 December 2018