Sistemik Etki İçin Nazal Yol

Yıl 2009, Cilt: 2 Sayı: 3, 7 - 14, 01.09.2009

Sevgi Güngör Yıldız Özsoy

Öz

Türkçe Özet:Nazal epitelin yüksek geçirgenliği, geniş absorpsiyon alanının varlığı, kan akımının hızlı olması gibi avantajları ile nazal yol; sistemik etki için pek çok ilacın alternatif veriliş yolu haline gelmiştir. İlacın nazal mukozadan geçişinde pek çok faktör rol oynamaktadır. Bu faktörler arasında başta etkin maddenin molekül ağırlığı gelmektedir. Düşük molekül ağırlığına sahip nazal uygulanan ilaçlar eczane raflarında yerini alırken, son yıllarda yüksek molekül ağırlığına sahip ilaçların (peptit ve protein) da nazal verilişi yaygın olarak araştırılmaktadır. Yapılan çalışmalar nazal yolla kullanılan penetrasyon arttırıcı maddelerin, ilaçların nazal mukozadan geçişinde son derece etkin olduğunu göstermiştir. Diğer bir yaklaşım da formülasyonlarda yeni ilaç taşıyıcı sistemlerin (emülsiyon, mikroemülsiyon, lipozom, insert, mikro- ve nanopartiküller) kullanılmasıdır. Bu derlemede, nazal yolun özellikleri, mukus sekresyonu ve mukosiliyer klerens, nazal mukozadan ilacın absorpsiyonunu etkileyen faktörler, nazal mukozadan geçiş ve geçişin arttırılması ve yeni nazal dozaj şekilleri ele alınmıştır.

Anahtar Kelimeler

nazal yol, nazal absorpsiyon, nazal dozaj şekilleri.

Sistemik Etki İçin Nazal Yol

Öz

AbstractNasal Route for Systemic Effect Nasal route has become an alternative route of delivery for a large number of drugs to produce systemic effect as it possesses advantageous such as high permeability, wide area of absorption, rapid blood flow. A numerous parameters play important role in drug transport through the nasal mucosa. Among of these factors, molecular weight of drugs is the most important one. While the low molecular weight drugs in nasal forms with systemic effect are currently taking place in the shelves of pharmacy stores, nasal administration of high molecular weight drugs (e.g. peptide and proteins) have also been widely investigated. The studies conducted on the subject indicated that the penetration enhancers for nasal delivery are highly effective in the transport of drugs through nasal mucosal membrane. Another approach is to use the novel drug carriers (emulsions, microemulsions, liposomes, inserts, micro- and nanoparticulates) in formulations for nasal delivery. In this article, the properties of nasal route, mucus secretion, mucociliary clearance, parameters affecting nasal drug absorption, transport mechanisms across nasal mucosa, enhancement of drug transport, and novel nasal dosage forms were reviewed.

Anahtar Kelimeler

nasal route, nasal absorption, nasal dosage forms.

Kaynakça

• Ozsoy Y. Particulate carriers for nasal administration. Kumar, M.N.V.R., Handbook 0f Particulate Drag Delivery; Vol. 2, Chapter 8, CA, USA: American Scientific Publisher, 2008:143- 92.
• Graft CL, Pollack GM. Nasal drug administration: potential for targeted central nervous system delivery. J Pharm Sci 2005; 94:1187—95.
• Belıl CR, Pimplaskar HK, Sileno AP, deMeireles J, Romeo VD. Effects ol' physicochemical properties and other factors oıı systemic nasal drug delivery. Adv Drug Del Rev 1998; 29: 89—116.
• lllum L. Nasal drug delivery—possibilities, problems and solutions. ] Control Rel 2003; 87: 187—98.
• Ozer Y. Alternative applications for drug delivery: nasal and pulmonary routes. Mozafari MR. Nanomaterials and Nanosystems for Biomedical Applications. Dordrecht: Springer, 2007: 99-112.
• Wermeling DP Miller JL. lntranasal drugr delivery. Rathbone MJ, Hadgraft J, Roberts MS. Modified Release Drug Delivery Technology, Chapter 61, New York: Marcel Dekker, Inc., 2002: 727—48.
• Arora P, Sharma S, Garg S. Permeability issues in nasal drug delivery. Drag Discov Today 2002; 7: 967—75.
• Ingemann M, Frokjaer S, Hovgaard L, Brondsted H. Peptide and protein drug delivery systems for non— parenteral routes of administration. Frokjaer S, Hovgaard Pharmaceutical Formulation Development of Peptides and Proteins, Chapter 10 Philadelphia: Taylor&Francis, 2000: 189-205 .
• Balakrishna S, Yadav AV, Aeavhat AM, Malayandi R. Bioavaliability of intranasal drug delivery system. Asian ] Pharrn 2009; 201-15.
• Jadhav KR, Gambhire MN , Shaikh IM, Kadam VJ , Pisal SS. Nasal drug delivery system-factors affecting and applications. Curr Drug Therapy 2007; 2: 27—38.
• Yamamoto A. Morita T, Hashida M, Sezaki H. Effect of absorption promoters on the nasal absorption of drugs with various molecular weights. Int J Pharm 1993; 93: 91—9.
• Hussain A, Hamadi S, Kagoshima M, lseki K, Dittert L. Does increasing the lipohiliciLy of peptides enhance their nasal absorption. J Pharm Sci 1991; 80: 1180—1.
• Washington N, Washington C, Wilson CG. Nasal drug delivery, Washington N, Washington C, Wilson CG. Physiological pharmaceutics barriers to drug absorption, 2nd Ed., London, Taylor&Francis, 1989: 199-220.
• Ozsoy Y, Gungor S, Cevher E. Nasal delivery of high molecular weight drugs, Molecules 2009;] 4: 3754—79.
• Newman SP, Steed KP, Hardy JG, Wilding IR, Hooper G,
• Ozsoy Y, 'l'unçel 'l', Can A, Akev N, Birteksöz S, Gerçeker
• A. In vivo studies on nasal preparations of ciprofloxacin
• Taş Ç, Özkan CK, Savaşer A, Özkan Y, Taşdemir U,
• Altunay H. Nasal absorption of metoclopramide from
• Taş Ç, Özkan CK, Savaşer A, Özkan Y, Taşdemir U,
• Yazan Y, Özer AY, Erol K. Pharmacodynamic comparison
• of a nasal formulation of verapamil and intravenous and oral dosage forms. Drug Dev Ind Pharm 1998; 22: 281—4.
• Yetkin G, Celebi N, Özognl C, Demiryürek AT.
• Davis SS, Illum L. Absorption enhancers for nasal drug
• delivery. Clin Pharmacokiner 2003;42: 1107—28.
• Türker S, Onur E, Özer Y. Nasal route and drug delivery
• Aikawa K, Matsumoto K, Uda H, Tanaka S, Shimamura H,
• Aramaki Y, Tsuehiya S. Prolonged release of drug from o/w
• Ko KT, Ncedham TE, Zia H. Emulsion formulations of
• testosterone for nasal administration. J Microeneapsııl 1998;
• Mitra R, Pezron I, Chu WA, Mitra AK. Lipid emulsions as
• vehicles for enhanced nasal delivery of insulin. Int J Pltarm
• Karasulu E, Yavaşoğlu A, Evrenşanal Z, Uyanıkgil Y,
• Karasulu HY. Permeation studies and histological examination of sheep nasal mucosa following administration of different nasal formulations with or without absorption enhancers. Drug Delivery 2008; 15:219-25.
• Li L, Nandi I, Kim KH. Development of an ethyl
• laurate—based microemulsion for rapid-onset intranasal
• Song KH, Chung SJ, Shim CK. Preparation and
• evaluation of proliposonıes containing salmon
• Mclnnes FJ , Thapa P, Baillie AJ, Welling PG, Watson
• DG, Gibson I, Nolan A. Stevens HN. In vivo evaluation
• Bertram C, Bodmeier R. Parameters affecting the drug
• release from in situ gelling nasal inserts. Eur J Pharm
• Gürcan D, Okyar A, Özbek B, Baktır G, Gerçeker A,
• Özsoy Y. Nasal Administration of Ciprofloxacin HCl
• LA) LII Hasçiçek C, Gönül N, Erk N. Mueoadhesive
• microspheres containing gentamicin sulphate for nasal
• Gungor S, Okyar A, Erturk—Toker S, Baktir G, Ozsoy Y.
• Ondansetron—loaded biodegradable microspheres as a
• Jadhav KR, Gambhire MN, Shaikh IM, Kadam V J , Pisal
• SS. Nasal Drug Delivery System—Factors Affecting and Applications. Current Drug Therapy 2007; 2: 27—38.