International Journal of Pharmaceutics 326 (2006) 107–118 Formulation of an antispasmodic drug as a topical local anesthetic Sameh M. Abdel-Hamid a,∗ , S.E. Abdel-Hady a , A.A. El-Shamy a , H.F. El-Dessouky b a Department of Drug Technology, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo, Egypt b Department of Oral Medicine, Diagnosis and Periodontology, Faculty of Dentistry, Ain Shams University, Abassia, Cairo, Egypt Received 20 April 2006; received in revised form 3 July 2006; accepted 7 July 2006 Available online 22 July 2006 Abstract Mebeverine hydrochloride, a spasmolytic agent on GIT smooth muscles, was reported to have a local anesthetic effect. Thus, it was desired in this study to formulate mebeverine HCl into a gel that could be used locally in the treatment of different oral painful conditions. Poloxamer 407 (P-407) was used as the base for this gel. Different additives were used to enhance drug release from the preparation while others were used to enhance the residence time for the preparation. Different formulae were characterized in terms of drug release and mucoadhesion. The formula which has shown the best compromise between the aforementioned parameters was selected for clinical evaluation in comparison to Lidocaine HCl gel ® and rheologically examined. The best drug release enhancer was cetrimide (0.005%, w/w), while hydroxypropylcellulose (0.5%, w/w) as a mucoadhesive additive has shown the best compromise between fast drug release and mucoadhesion. The gel formula (G) has shown a better pain reduction efficiency (p = 0.0078) and longer duration (p = 0.0313) than Lidocaine HCl gel ® . Histopathological examination has shown no change in the inflammatory cells count of rat oral mucosa. Therefore, it could be concluded that (G) is very promising as a local anesthetic preparation for the treatment of different oral painful conditions. © 2006 Elsevier B.V. All rights reserved. Keywords: Mebeverine HCl; Local anesthetic; Gel; Oral painful conditions; Histopathology 1. Introduction Mebeverine is a musculotropic antispasmodic agent used for the symptomatic treatment of abdominal pain, bowel dis- turbances and intestinal discomfort related to irritable bowel syndrome (Ritchie and Truelove, 1980; Subissi et al., 1983). Mebeverine hydrochloride has shown efficacy in the treatment of the irritable bowel syndrome when prepared in different dosage forms including tablets (Inauen and Halter, 1994) and rectal solu- tion (Abdel-Hady et al., 2003). It has also been used successfully in capsule form in reducing the severity of pain in patients with primary dysmenorrhea (Langrick et al., 1989). Mebeverine is also available in the market in other forms such as suspension and effervescent granules. However, mebeverine has never been used before as a local anesthetic. It has been reported that mebeverine HCl exerts a local anesthetic action by blocking voltage operated sodium chan- ∗ Corresponding author. Tel.: +202 6424 807; fax: +202 4051 107; mobile: +2010 1056 369. E-mail address: samoh78@hotmail.com (S.M. Abdel-Hamid). nels, an action similar to lidocaine (Den Hertog and Van den Akker, 1987). Moreover, mebeverine was approximately twice as potent and produced a longer duration of local anesthetic activity than did procaine using the mouse-tail local anesthetic test (Czechowicz et al., 1969). Although mebeverine has a strong local anesthetic activity, on the contrary to other local anesthet- ics it was reported to have non-significant central or peripheral side effects (Connell, 1965; Van Outryve et al., 1995; Gilbody et al., 2000) with LD 50 1 g/kg in mice (Radwan et al., 1998). Fur- thermore, it has shown rapid and facile hydrolysis on reaching circulation (Dickinson et al., 1991). Compared to other locally applied periodontal solid devices like fibers, tablets or microparticles, gels are easily prepared, highly biocompatible with a lower risk of inflammation or adverse reactions, easily applied and do not need to be removed (Esposito et al., 1996). Furthermore, gels often provide a faster release of drug substance, independent of the water solubility of the drug, as compared to creams and ointments (Nairn, 2000). Also, gel vehicles containing therapeutic agents are especially useful for application to mucous membranes and ulcerated or burned tissues, because their high water content reduces irri- tancy. Furthermore, gels are easily removed by gentle rinsing 0378-5173/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2006.07.028