Radioactive Permeability Studies of Doxycycline Hyclate from Microemulsion and Solution

Year 2016, Volume: 20 Issue: 2, 116 - 121, 09.02.2016

Derya İlem-özdemir , Evren Gündoğdu Meliha Ekinci , Makbule Aşıkoğlu

Abstract

Doxycycline Hyclate (DOX) is an antibacterial drug which is member of the second tetracycline group and the absorption of DOX is reduced about 20% in the presence of skimmed milk. Therefore new drug delivery system can be advisable for DOX to reduce the food and drug interaction and improve the bioavailability.  The aim of the present study is to prepare a microemulsion system of DOX which could result in reducing in food interaction and an improvement of oral bioavailability by increasing the drug's permeability. For this purposes, DOX was radiolabeled with ^99mTc. Radiochemical purity was determined with radioactive thin layer chromatography (RTLC) studies. Permeability of DOX from ^99mTc-DOX solution (^99mTc-DOX-S) and ^99mTc-DOX loaded microemulsion (^99mTc-DOX-M) was investigated with in vitro cell culture studies by using human colonic adenocarcinoma cell line (Caco-2). The radioactivity of ^99mTc-DOX-M for the apical to basolateral direction (P_app (A→B)) and basolateral to apical direction (P_app (B→A)) were found higher than ^99mTc-DOX-S. Based on the in vitro cell culture studies, this dosage form is a promising formulation as an alternative for oral drug delivery of DOX. 

Keywords

Doxycycline Hyclate, Permeability, caco-2

Derya Ilem-Ozdemir, Evren Gundogdu, Meliha Ekinci, Makbule Asikoglu

Abstract

References

• Peter G. Welling, Patricia A. Koch, Curtis C. Lau and William A. Craig. Bioavailability of Tetracycline and Doxycycline in Fasted and Nonfasted Subjects. doi: 10.1128/AAC.11.3.462.Antimicrob. Agents Chemother.March 1977 vol. 11 no. 3 462-469
• A. C. Kogawa, H. R. Nunes Salgado, Doxycyclıne Hyclate: A Revıew Of Propertıes, Applıcatıons And Analytıcal Methods International Life Science And Pharma Research, Issn 2250-0480 Vol 2/Issue 4/Oct-Dec 2012
• E. Dahl .Doxycycline use in maritime-medical practices. Int Marit Health 2015; 66, 3: 121–122.
• N Kenneth. and A. MacGowan. Pharmacokinetics and pharmacodynamics of the tetracyclinesincluding glycylcyclines. Journal of Antimicrobial Chemotherapy.2006. 58, 256–265.
• Ilem-Ozdemir D., Asikoglu M., Guneri T., Koseoglu K., Ozkilic H. Evaluation Bone Uptake of Alendronate Sodium Via Vaginal Route by Gamma Scintigraphy, Vaginal Uptake of Alendronate Sodium Journal of Drug Delivery Science and Technology. 10/2013; 24(2):218-221.
• M. Jayne Lawrencea, G. D. Reesb, Microemulsion-based media as novel drug delivery systems Advanced Drug Delivery Reviews 45 (2000) 89–121
• NÜ Okur, Dİ Özdemir, ŞG Kahyaoğlu, ZA Şenyiğit, M Aşıkoğlu, L Genç, HY Karasulu. Assessment of Aprotinin Loaded Microemulsion Formulations for Parenteral Drug Delivery: Preparation, Characterization, in vitro Release and Cytotoxicity Studies. Curr Drug Deliv. 2015;12(6):668-79. PubMed PMID: 26306401.
• H. Y. Karasulu, N. Oruç, N. Üstündağ-Okur, D. İlem Özdemir, Z. Ay Şenyiğit, F. Barbet Yılmaz, M. Aşıkoğlu, H. Özkılıç, E. Akçiçek, T. Güneri, Ö. Özütemiz. Aprotinin revisited: Formulation, characterization, biodistribution and therapeutic potential of new aprotinin microemulsion in acute pancreatitis. Journal of Drug Targeting 03/2015; 23(6):1-13.
• KR Jadhav et al. Applications of microemulsion based drug delivery system. Curr Drug Deliv 2006; 3(3): 267-273.
• JA. Krauser (2013) A perspective on tritium versus carbon-14: ensuring optimal label selection in pharmaceutical research and development. J Labelled Comp Radiopharm. 56(9-10): 441–6.
• YS Krishnaiah, S Satyanarayana, YV Rama S Prasad, Narasimha Rao. Gamma scintigraphic studies on guar gum matrix tablets for colonic drug delivery in healthy human volunteers. J Control Release, 1998.13;55(2-3):245-52.
• T. Marvola, J. Marvol, H. Kanerva, A. Ahonen, K. Lindevall, M. Marvola Neutron activation based gamma scintigraphic evaluation of enteric-coated capsules forlocal treatment in colon. Int J Pharm. 2008. 12;349(1-2):24-9.
• D. Ilem-Özdemir, M. Asikoglu, H. Ozkili, F. Yilmaz, M. Hosgor-Limoncu, S. Ayhan. Tc-99m-Doxycycline hyclate: a new radiolabeled antibiotic for bacterial infection imagingJournal of Labelled Compounds and Radiopharmaceuticals.. 01/2014; DOI: 10.1002/jlcr.3135.
• D. İlem-Özdemir, M. Aşıkoğlu, H. Özkılıç. Radiolabeling, quality control and kit formulation of a new 99mTc-labeled antibiotic: 99mTc-doxycycline hyclate. Journal of Radioanalytical and Nuclear Chemistry. 12/2013; 298(3). DOI: 10.1007/s10967-013-2547-2
• Y. Baspinar, C.M. Keck, H.H. Borchert, Development of a positively charged prednicarbate nanoemulsion. INTERNATIONAL JOURNAL OF PHARMACEUTICS 2010:383:1-2.201-208.
• Wahlang B1, Pawar YB, Bansal AK. Identification of permeability-related hurdles in oral delivery of curcumin using the Caco-2 cell model. Eur J Pharm Biopharm. 2011 Feb;77(2):275-82.