Research article Rapports De Pharmacie Vol.2 (2), 2016, 251-264 ISSN: 2455-0507 251 OPTIMIZATION AND CHARACTERIZATION OF OXYMETAZOLINE BASED THERMOSENSITIVE IN SITU GEL FOR NASAL DRUG DELIVERY BY USING STAT-EASE DESIGN-EXPERT SOFTWARE Jaya Raja Kumar Faculty of Pharmacy, AIMST University, Semeling, Bedong, Malaysia ABSTRACT This work was focused on the optimization and characterization of temperature reverse in situ gels based on poloxamer 188, a thermosensitive polymer, and hydroxypropylmethylcellulose (HPMC), a bioadhesive polymer, planned for the nasal delivery of oxymetazoline hydrochloride. Seventeen runs of temperature reverse in situ gels s were composed of poloxamer 188 and HPMC. A 3-factor, 4-level Box-Behnken design was used to optimize the process parameters including Poloxamer 188 (A), HPMC (B) and Distilled water (C). Four dependent variables gel strength, mucoadhesive force, gelation time and gelation temperature was measured as responses. Gel strength of in situ gel was found to be in the range of 75-120 seconds. The mathematical model generated for mucoadhesive force was found to be significant with F-value of 362.28 (p < 0.0001) and R 2 value of 0.9979. The gelation time was found to be significant with F-value of 80.29 implies the model is significant. The interactive effect of A and B on the gelation temperature (GT) at fixed level of C. At low levels of A (P188), GT increased from 43.1 to 44.2 ºC. Similarly, at high levels of A, Gelation temperature increases from 54.1 to 56.3 ºC, but moderate level of A, the system gel at body temperature. Keywords: Thermosensitive in situ gel, HPLC, Rabbit Model, Box-Behnken design INTRODUCTION Oxymetazoline hydrochloride (6-tert-Butyl-3-(4,5- dihydro-1H-imidazol-2-ylmethyl)-2,4-dimethylphenol hydrochloride) is an imidazoline derivative sympathomimetic amine. Oxymetazoline (OXY) is a vasoconstrictor that acts directly on nasal membranes and has been available as a over-the- counter intranasal drug in the United States for more than 40 years. It is approved for the relief of nasal congestion as a result of common colds and allergic rhinitis. Excessive doses of nonprescription oxymetazoline nasal products have been associated with cardiovascular and/or central nervous system adverse events, indicating systemic absorption from the nasal mucosa. [1-3]. Allergic rhinitis (AR), also known as hyper aesthetic rhinitis, is an allergic inflammatory disease that is caused by a variety of allergens. Allergic rhinitis is an allergic reaction that frequently appears in nasal passages during the spring, autumn and winter [4]. The clinical symptoms of allergic rhinitis are unlike in various people, but the foremost symptoms are nasal itching, sneezing and a runny, blocked nose. The intranasal administration of drugs has long been used for the treatment of rhinitis and nasal congestion. Intranasal administration can overcome the side effects that happen in the gastrointestinal tract and the hepatic first-pass effect. Furthermore, drugs are absorbed better, because of the abundant blood and lymphatic capillaries under the nasal mucosa. Since these properties, intranasal administration can effectively enhance the bioavailability of drugs. Intranasal administration has been stated to reach comparable blood concentrations as intravenous administration [5]. Most of the commercially available nasal preparations are now sprays. The scavenging effect of nasal cilia leads to a very short drug residence time on the human nasal mucosal surface (only 15–30 min) [6], which affects the clinical efficacy to some extent. The in situ gel is made of polymeric materials that have a solution state that responds to external stimuli at the administration spot. These formulations also have conformations that can undergo reversible conversion to form a semisolid [7]. In situ gel types include thermo-sensitive, ion-activated and pH responsive. The most extensive and mature type of in situ gel currently used in research is the gel that reacts to changes in temperature, called a “temperature- sensitive in situ gel”. A temperature-sensitive in situ gel is liquid or semisolid at room temperature and congeals into gel as the temperature increases from room temperature to body temperature, which results in good adhesion and slow release effects [8,9]. The polymers under thermo-sensitive include chitosan, pluronics, tetronics, xyloglucans, and Address for correspondence: Dr.Jaya raja Kumar Faculty of Pharmacy,, AIMST University, Semeling- 08100, Bedong, Malaysia.