Journal of Literature Pharmacy Sciences

Mikro ve Nanoemülsiyonların Farmasötik Yönden Değerlendirilmesi
Evaluation of Micro and Nanoemulsions in Pharmaceutical Aspect
Emine Dilek ÖZYILMAZa, Özgün SAYINERb, Tansel ÇOMOĞLUb
aDoğu Akdeniz Üniversitesi Eczacılık Fakültesi, Farmasötik Teknoloji ABD, Gazimağusa, KKTC
bAnkara Üniversitesi Eczacılık Fakültesi, Farmasötik Teknoloji ABD, Ankara, TÜRKİYE
J Lit Pharm Sci. 2020;9(1):65-76
doi: 10.5336/pharmsci.2019-66287
Article Language: TR
Full Text
ÖZET
 Son yıllarda emülsiyon tipi ilaç taşıyıcı sistemler üzerine araştırmalar yoğunlaşmaktadır. Gerek hazırlama yöntemlerinin göreceli olarak kolaylığı gerek mikroemülsiyonlarda olduğu gibi kararlılığı yüksek formülasyonların elde edilebilmesi ve farmasötik uygulamalarda ve endüstriyel ölçeklendirmede kolay yer bulabilmeleri nedeni ile sıklıkla tercih edilen ilaç taşıyıcı sistemler olarak tanımlanmaktadırlar. Başarılı bir emülsiyon formülasyonunun geliştirilmesinde en önemli etken, uygun bir emülgatör seçilmesidir. Emülsiyon tipi ilaç taşıyıcı sistemleri; klasik emülsiyonlar, mikroemülsiyonlar ve nanoemülsiyonlar olarak inceleyebiliriz. Mikro ve nanoemülsiyon kavramları yaygın olarak birbiri yerine kullanılan 2 kavram olmakla birlikte, bu 2 kavram arasında terminolojik, formülasyon süreçleri, damlacık boyutu-şekli ve stabiliteleri bakımından temel farklılıklar bulunmaktadır. Mikroemülsiyonlar; berrak, termodinamik olarak kararlı, izotropik sıvı karışımlardır. Yağ, su, yüzey etken madde ve yardımcı yüzey etken madde kullanılarak hazırlanırlar. Geleneksel emülsiyonlara oranla nano boyuta kadar inebilen çok küçük damlacıkları içerirler. Mikroemülsiyonlar, enerji gereksinimi olmadan kendiliğinden oluşmaları, stabilitelerinin yüksek olması, yüksek çözündürme kapasitesine sahip olmaları ve hızlı bir şekilde emilerek, yüksek biyoyararlanım göstermeleri nedeni ile hem ilaç hem de kozmetik alanda sıklıkla tercih edilen emülsiyon şekilleridir. Nanoemülsiyonlar ise nano ölçekli damlacıkların dağılımı yönünden mikroemülsiyonlara çok benzemekle birlikte, kendiliğinden oluşan mikroemülsiyonlardan farklı olarak mekanik kuvvet uygulanarak üretilirler. Nanoemülsiyonlar, hazırlanmalarında çok daha az miktarda yüzey etken maddeye ihtiyaç duyulması ve filtrasyonla sterilizasyona imkân sağlamaları gibi avantajlara sahiptirler. Bu çalışmada, mikro ve nanoemülsiyonların özelliklerinden, sağladıkları avantaj ve dezavantajlardan, formülasyon bileşenlerinden, hazırlanma yöntemlerinden ve kullanım alanlarından söz edilerek, emülsiyon sistemleri karşılaştırmalı olarak değerlendirilecektir.

Anahtar Kelimeler: Mikroemülsiyon; nanoemülsiyon; emülsiyon hazırlama yöntemleri; mikroemülsiyon ve nanoemülsiyonlar arasındaki farklar; mikro ve nanoemülsiyonların kullanım alanları
ABSTRACT
 In recent years, research on emulsion type drug delivery systems has been intensified. They are often defined as preferred drug delivery systems because of the relatively ease of preparation methods and the ability to obtain stable formulations, such as microemulsions, and their availability in pharmaceutical applications and industrial scaling. The most important factor in the development of an ideal emulsion formulation is the selection of a suitable emulsifier. Emulsion- type drug delivery systems; classical emulsions, microemulsions and nanoemulsions. Although micro and nanoemulsion concepts are commonly used interchangeably, there are fundamental differences between these two concepts in terms of terminological, formulation processes, droplet size-shape and stability. Microemulsions; are clear, thermodynamically stable, isotropic liquid mixtures. They are prepared using oil, water, surfactant and cosurfactant. They contain very small droplets that can go down to nano size compared to conventional emulsions. Microemulsions are frequently preferred emulsion forms in both pharmaceutical and cosmetic fields because they form spontaneously without energy requirement and they have high stability, high dissolution capacity and high bioavailability by absorbing rapidly. Nanoemulsions are similar to microemulsions in terms of the distribution of nano-scale droplets, but they are produced by applying mechanical force unlike microemulsions. Nanoemulsions have the advantage that they require a much smaller amount of surfactant in their preparation and allow filtration sterilization. In this review, the characteristics, advantages and disadvantages, formulation components, methods of preparation and uses of the micro and nanoemulsions will be evaluated comparatively.

Keywords: Microemulsion; nanoemulsion; emulsion preparation methods; differences between microemulsion and nanoemulsions; application areas of micro and nanoemulsions
REFERENCES:
  1. Çelebi N. [Emulsions]. Acartürk F, Ağabeyoğlu İ, Çelebi N, Değim T, Değim Z, Doğanay T, et al, editörler. Modern Farmasötik Teknoloji. 2. Baskı. Ankara: TEB Eczacılık Akademisi; 2009. p.277-99.
  2. Çomoğlu T, Gönül N. Microemulsions. J Fac Pharm. 1997;26(2):95-108.
  3. Li H, Pan T, Cui Y, Li X, Gao J, Yang W, et al. Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique. Int J Nanomed. 2016;11(1):3777-88. [Crossref]  [PubMed]  [PMC] 
  4. Shah P, Bhalodia D, Shelat P. Nanoemulsion: a pharmaceutical review. Systematic Reviews in Pharm. 2010;1(1):24-32. [Crossref] 
  5. Anton N, Vandamme TF. Nano-emulsions and micro-emulsions: clarifications of the critical differences. Pharm Res. 2011;28(5):978-85. [Crossref]  [PubMed] 
  6. McClements DJ. Nanoemulsions versus microemulsions: terminology, differences, and similarities. The Royal Society of Chem. 2012;8(1):1719-29. [Crossref] 
  7. Mason TG, Wilking JN, Meleson K, Chang CB, Graves SM. Nanoemulsions: formation, structure, and physical properties. J Physics. 2006;18(41):635-66. [Crossref] 
  8. Solans C, Solé I. Nano-emulsions: formation by low-energy methods. Curr Opin Colloid Int Sci. 2012;17(5):246-54. [Crossref] 
  9. Tadros T, Izquierdo P, Esquena J, Solans C. Formation and stability of nano-emulsions. Adv Colloid and Int Sci. 2004;108:303-18. [Crossref]  [PubMed] 
  10. Tiwari SB, Amiji MM. Improved oral delivery of paclitaxel following administration in nanoemulsion formulations. J Nanosci Nanotechnol. 2006;6(9-10):3215-21. [Crossref]  [PubMed] 
  11. Karasulu HY. Microemulsions as novel drug carriers: the formation, stability, applications and toxicity. Expert Opin Drug Deliv. 2008;5(1):119-35. [Crossref]  [PubMed] 
  12. Nastiti CMRR, Ponto T, Abd E, Grice JE, Benson HAE, Roberts MS. Topical nano and microemulsions for skin delivery. Pharmaceutics. 2017;9(4):37. [Crossref]  [PubMed]  [PMC] 
  13. Muzaffar F, Singh US, Chauhan L. Review on microemulsion as futuristic drug delivery. Int J Pharm Pharm Sci. 2013;5(3):39-53.
  14. Danielsson I, Friman R, Sjöblom J. Equilibria and structures of microemulsions and liquid crystals in water-surfactant-oil systems. J Colloid and Int Sci. 1982;85(2):442-51. [Crossref] 
  15. Kreilgaard M. Influence of microemulsions on cutaneous drug delivery. Adv Drug Deliv Rev. 2002;54 Suppl 1:S77-98. [Crossref] 
  16. Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Colloid Interface Sci. 2006;123:369-85. [Crossref]  [PubMed] 
  17. Santos P, Watkinson AC, Hadgraft J, Lane ME. Application of microemulsions in dermal and transdermal drug delivery. Skin Pharmacol Physiol. 2008;21(5):246-59. [Crossref]  [PubMed] 
  18. Lee KL. Applications and use of microemulsions. J Power Sour. 2010;195(6):135-49.
  19. Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev. 2012;64:175-93. [Crossref] 
  20. Jha SK, Dey S, Karki S. Microemulsions-potential carrier for improved drug delivery. Asian J Biomed Pharm Sci. 2011;1(1):39-52.
  21. Constantinides PP. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res. 1995;12(11):1561-72. [Crossref]  [PubMed] 
  22. Akhtar N, Khan RA. Liposomal systems as viable drug delivery technology for skin cancer sites with an outlook on lipid-based delivery vehicles and diagnostic imaging inputs for skin conditions'. Prog Lipid Res. 2016;2(1):192-230. [Crossref]  [PubMed] 
  23. Moghimipour E, Salimi A, Eftekhari S. Design and characterization of microemulsion systems for naproxen. Adv Pharm Bull. 2013;3(1):63-71.
  24. Jain J, Fernandes C, Patravale V. Formulation development of parenteral phospholipid-based microemulsion of etoposide. AAPS PharmSci. 2010;11(2):826-31. [Crossref]  [PubMed]  [PMC] 
  25. Pratap SB, Brajesh K, Jain SK, Kausar S. Development and characterization of a nanoemulsion gel formulation for transdermal delivery of carvedilol. Int J Drug Dev Res. 2012;4(1):151-61.
  26. Koroleva MY, Yurtov EV. Nanoemulsions: the properties, methods of preparation and promosing applications. Russian Chemical Rev. 2008;81(1):21-43. [Crossref] 
  27. Kale SN, Deore SL. Emulsion micro emulsion and nano emulsion: a review. Syst Rev Pharm. 2017;8(1):39-47. [Crossref] 
  28. Mahajan HS, Mahajan MS, Nerkar PP, Agrawal A. Nanoemulsion-based intranasal drug delivery system of saquinavir mesylate for brain targeting. Drug Deliv. 2014;21(2):148-54. [Crossref]  [PubMed] 
  29. Baboota S, Shakeel F, Ahuja A, Ali J, Shafiq S. Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib. Acta Pharm. 2007;57(3):315-32. [Crossref]  [PubMed] 
  30. Bhosale RR, Osmani RA, Ghodake PP, Shaikh SM, Chavan SR. Nanoemulsion: a review on novel profusion in advanced drug delivery. Indian J Pharm Biol Res. 2014;2(1):122-7. [Crossref] 
  31. Loureiro A, Abreu AS, Sárria MP, Figueiredo MC, Saraiva LM, Bernardes GJ, et al. Functionalized protein nanoemulsions by incorporation of chemically modified BSA. RSC Adv. 2015;5(7):4976-83. [Crossref] 
  32. Xia F, Fan W, Jiang S, Ma Y, Lu Y, Qi J, et al. Size-dependent translocation of nanoemulsions via oral delivery. ACS Applied Mat Inter. 2017;9(26):21660-72. [Crossref]  [PubMed] 
  33. Colombo M, Figueiró F, de Fraga Dias A, Teixeira HF, Battastini AMO, Koester LS. Kaempferol-loaded mucoadhesive nanoemulsion for intranasal administration reduces glioma growth in vitro. Int J Pharm. 2018;543(1-2):214-23. [Crossref]  [PubMed] 
  34. Kumar M, Misra A, Babbar AK, Mishra AK, Mishra P, Pathak K. Intranasal nanoemulsion based brain targeting drug delivery system of risperidone. Int J Pharm. 2008;358(1-2):285-91. [Crossref]  [PubMed] 

.: Up To Date

.: Process List

Login

 Forgot your password?

 New Registration  

Contact

Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com