Drug Development and Industrial Pharmacy, 2010; 36(11): 1330–1339 ISSN 0363-9045 print/ISSN 1520-5762 online © Informa UK, Ltd. DOI: 10.3109/03639041003801885 http://www.informapharmascience.com/ddi LDDI ORIGINAL ARTICLE Development of dorzolamide hydrochloride in situ gel nanoemulsion for ocular delivery Dorzolamide hydrochloride in situ gel nanoemulsion H.O. Ammar 1 , H.A. Salama 1 , M. Ghorab 2 and A.A. Mahmoud 1 1 Department of Pharmaceutical Technology, National Research Centre Dokki, Cairo, Egypt and 2 Department of Pharmaceutics, Faculty of Pharmacy, Cairo University, Cairo, Egypt Abstract Background: Several in situ gel-forming systems have been developed to prolong the precorneal resi- dence time of a drug and to improve ocular bioavailability. Poloxamer 407 with its thermoreversible gela- tion and surface active properties was utilized to formulate a novel dorzolamide hydrochloride in situ gel nanoemulsion (NE) delivery system for ocular use. Objective: Improvement of both ocular bioavailability and duration of action for dorzolamide hydrochloride was the aim of this study. Methods: Physicochemical properties, in vitro drug release studies and biological evaluation of the prepared NEs were investigated. Results: The optimum formulation of in situ gel NE consisted of Triacetin (7.80%), Poloxamer 407 (13.65%), Poloxamer 188 (3.41%), Miranol C2M (4.55%), and water (70.59%). Biological evaluation of the designed dorzolamide formulation on normotensive albino rabbits indicated that this formulation had better bio- logical performance, faster onset of action, and prolonged effect relative to either drug solution or the market product. The formula showed a superior pharmacodynamic activity compared to the in situ gel dorzolamide eye drops. This indicated the effectiveness of the in situ gel properties of poloxamer 407, besides formulating the drug in an NE form for improving the therapeutic efficacy of the drug. Conclusion: These results demonstrate the superiority of in situ gel NE to conventional ocular eye drops and in situ gels to enhance ocular drug bioavailability. Key words: Bioavailability; dorzolamide hydrochloride; in situ gel; nanoemulsion; ocular Introduction Glaucoma is a serious eye disorder characterized by an increase in intraocular pressure (IOP), which results in damage to the optic disc 1 , and thus leads gradually to loss of vision, usually without symptoms. Furthermore, it is the second leading cause of blindness worldwide 2,3 . It is believed that glaucoma is the result of an imbalance between aqueous humor secretion and drainage pro- cesses within the ocular chambers 4 . Dorzolamide hydrochloride is a carbonic anhydrase inhibitor used in the treatment of glaucoma. Carbonic anhydrase inhibitors reduce IOP by decreasing aqueous humor secretion through the inhibition of carbonic anhydrase isoenzyme II in the ciliary processes 5 . Topi- cally effective aqueous dorzolamide eye drop solution (Trusopt ® ) has become one of the most widely used medications for the treatment of open-angle glaucoma since it became commercially available in 1995 6 . The concentration of dorzolamide HCl in Trusopt ® is 2.2% (w/v), corresponding to 2.0% of the free base, pH 5.65. Hydroxyethyl cellulose is used to increase the viscosity of Trusopt ® eye drops; this increased viscosity leads to increased corneal contact time and, consequently, to increased bioavailability. However, the relatively low pH and high viscosity have been shown to generate local irri- tation after topical administration of the eye drops 7 and may be consistent with transient epithelial alteration 8 . The anatomy, physiology, and biochemistry of the eye render it highly impervious to foreign substances. The absorption of drugs in the eye is severely limited by some protective mechanisms that ensure the proper functioning of the eye and by other concomitant factors 9 . Several in situ gel-forming systems have been Address for correspondence: Dr. H.O. Ammar, Department of Pharmaceutical Technology, National Research Centre, Dokki, Cairo, Egypt. Tel: +2 012 4472851, Fax: +2 02 33370931. E-mail: husseinammar@hotmail.com (Received 24 Aug 2009; accepted 23 Mar 2010) Drug Development and Industrial Pharmacy Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 01/10/14 For personal use only.