JPP 2010, 62: 430–439 ß 2010 The Authors Journal compilation ß 2010 Royal Pharmaceutical Society of Great Britain Received August 05, 2009 Accepted Jan 07, 2010 DOI 10.1211/jpp/62.04.0004 ISSN 0022-3573 Correspondence: Dr Maria P.D. Gremião, School of Pharmacy of Araraquara, State University of Sao Paulo, Research Division, Araraquara, Sao Paulo, SP, Brazil. E-mail: pgremiao@fcfar.unesp.br Research Paper Surfactant systems for nasal zidovudine delivery: structural, rheological and mucoadhesive properties Flávia C. Carvalho a , Mariana S. Barbi a , Victor Hugo V. Sarmento b , Leila A. Chiavacci a , Flávia M. Netto c and Maria P.D. Gremia ˜o a a School of Pharmaceutical Sciences, State University of São Paulo, UNESP, Araraquara, b Federal University of Sergipe, UFS, Itabaiana, SE and c State University of Campinas UNICAMP, Campinas, SP, Brazil Abstract Objectives Zidovudine is the antiretroviral drug most frequently used for the treatment of AIDS. Although its effectiveness is recognized, it undergoes extensive first-pass metabolism and exhibits poor oral bioavailability. The nasal route is an option for enhanced therapeutic efficacy and to reduce the extent of the first-pass effect. There are some mechanisms that limit intranasal absorption, such as mucociliary clearance, which rapidly removes the formulation from the nasal cavity. To improve the nasal residence time of zidovudine on the nasal mucosa, we aimed to develop a mucoadhesive surfactant system for zidovudine nasal administration. Methods Systems composed of PPG-5-CETETH-20 as surfactant, oleic acid and water were characterized by polarized light microscopy, small-angle X-ray scattering and rheological measurements. Mucoadhesion was investigated by phase behaviour studies, rheological synergism and mucoadhesive strength determination. Key findings Results indicate that the original formulations were microemulsions that displayed phase transition to a lamellar phase when brought into contact with aqueous nasal simulated mucus. The phase transition was accompanied by an increase in system elasticity and, irrespective of phase behaviour, all the systems showed a good mucoadhesive force. Thus, a viscous and mucoadhesive liquid crystalline matrix could be formed when the formulations were in contact with simulated mucus, which may prolong the residence time of zidovudine in the nasal cavity. Conclusions These findings indicate a potentially useful system for nasal administration of zidovudine. Keywords liquid crystal; microemulsion; mucoadhesion; oscillatory rheology; phase behaviour Introduction The human immunodeficiency virus (HIV) pandemic remains the most serious infectious disease challenge to public health. The estimated number of people living with HIV worldwide in 2007 was 33.2 million. [1] Although antiretroviral drug therapy has contributed significantly to improvement of acquired immunodeficiency syndrome (AIDS) disease management, its current use is associated with several disadvantages and inconveniences to the patient. Zidovudine (AZT), the first anti-HIV compound approved for clinical use, is widely used for the treatment of AIDS, either alone or in combination with other antiviral agents. [2] However, the main limitations to the therapeutic effectiveness of zidovudine are its dose-dependent haematological toxicity, low therapeutic index, short biological half-life and poor bioavailability. [3] Owing to its short half-life, patients have to take frequent doses to maintain constant therapeutic drug levels. [2] The severe side effects associated with the complicated dosing schedules of antiretroviral therapy may be a cause of low adherence to the treatment. [2] Strategies currently being investigated to overcome these limitations include the design and development of novel drug delivery systems that can improve the efficacy of both existing and new antiretroviral drugs. [4] Novel drug delivery systems can be designed to administer drugs by alternative routes when the oral route is ineffective. Nasal drug delivery has generated widespread interest as an alternative route for drugs such as zidovudine that are susceptible to first-pass hepatic 430