Characterization of the interaction between Lomefloxacin and Certain Gastro-retentive Polymers Amir Ibrahim Mohamed a, Osama A. A. Ahmed b, Amira Osama c, Omar Anwar d. a Lecture in Military Medical Academy, Cairo, Egypt. b Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia. c Medical services Department, Cairo, Egypt. d Ministry of health, Cairo, Egypt. Introduction Sodium Alginate(SA), Ethyl Cellulose(EC), and Eudragit RS100 are examples of polymers commonly used in gastroretentive dosage forms. The main objective of this study was to investigate the possible effect of these polymers on the in-vitro anti-H.pylori activity of a third generation fluoroquinolone antibacterial agent; Lomefloxacin hydrochloride (LFX). To study the nature of polymer effect on drug activity; drug-polymer solid dispersions (blend films) were prepared by Solvent Casting technique and characterized by conventional techniques including DSC, XRD, FTIR analysis as well as by in- vitro drug release study in gastric environment. Fig. 1. Photomicrographs for (a) LFX alone, (b) LFX-Alginate film, (c) LFX- EC film, and (d) LFX- RS100 film. Conclusions The present study reveals that LFX-SA blend has the maximum anti-H. pylori activity as compared with free LFX or LFX-EC/RS100 blends. Results also conclude that blending of LFX with SA will increase its anti-H. pylori activity while blending with EC or RS100 will control LFX release rate in gastric pH. Thus formulation of LFX with these biocompatible and cost-effective polymers as gastro-retentive dosage forms (floating or mucoadhesive) can be used as stomach specific drug delivery system for eradication of H. pylori. Preparation of Drug-Polymer Blend Films For LFX- Alginate films, 5ml drug solution (5mg/ml) was mixed with 5ml Alginate solution (5mg/ml) to get a mixture of 1:1 w/w drug: polymer ratio. Then, the mixture obtained was caste to glass petri-dishes and evaporated at room temperature for 48 hrs. In case of Ethyl Cellulose, and Eudragit RS100 films, polymer was dissolved in acetone with agitation to a concentration of 1mg/ml. Then 2ml of drug solution (5mg/ml) was added slowly with stirring to 10ml Polymer solutions to get a mixture of 1:1 drug: polymer ratio. The mixtures obtained were caste to glass petri-dishes and evaporated at room temperature for 48 hrs. Differential scanning calorimetry (DSC) thermal analysis The thermograms of LFX-polymer blend films Figure(2) showed a complete disappearance of LFX T m peak for LFX-SA, minor shift (318 o C) for LFX-EC, and much more shift to lower value (286 o C) for LFX-RS100 blend film. These results indicate certain interactions between LFX and Sodium Alginate or Eudragit RS100 polymers during film preparation. Fig. 2. DSC Thermograms of (a) Pure LFX; (b) Polymer alone; (c) LFX-Polymer Physical mixture; (d) Polymer placebo film; (e) LFX-Polymer blend film. ( a ) ( b ) ( c ) ( d ) Fig. 4. Mueller-Hinton agar susceptibility test; (a) Series of agar plates containing serial dilutions of LFX, (b) Control plate showing H. pylori growth, (c & d) LFX plate showing growth inhibition. Fourier transform infrared (FTIR) spectral analysis LFX-polymer physical mixtures Table(1) showed the presence of all characteristic peaks of LFX which confirm the absence of interactions between drug and polymers in solid state. On the other hand, LFX-polymer blend films showed different changes according to polymer type which suggest certain binding between LFX and polymers. Based on chemical structure of LFX and polymers (SA, EC,& RS100), these binding could be attributed to various attraction forces such as hydrogen, ionic, and/or electrostatic bonding. X-ray diffraction analysis The X-ray patterns of LFX loaded films showed that blends prepared with EC & RS100 polymers still showed the typical signals of LFX crystals (at & diffraction angle), which indicate that LFX was able to re-crystallize in the polymer network films. In contrast, no crystalline peaks observed in LFX- SA film pattern either because LFX was dissolved in alginate film or was precipitated in an amorphous state. Table 1. Most effective FTIR bands of LFX and its Polymer Blends (cm -1 ). In-vitro release study The in-vitro release profile of LFX from SA, EC, or RS100 polymer blends revealed that the amount of drug released in 6 hrs was ranged from 93.2 to 99.2% which indicate that the drug-polymer binding not influence the concentration of free active drug released from all polymer blend films. The maximum LFX release was observed in LFX-SA blend (about 99.2% within 45minuts) while, LFX release profile from EC and RS100 blend films was biphasic pattern of release with an initial burst release of 61.4% and 43.2% in 1 hour, followed by a slower sustained release phase to the end of incubation period (97.2 & 93.2% after 6hrs). Fig. 3. Cumulative Percentage Release of LFX from Polymer blend films. Anti-H pylori activity of Lomefloxacin-polymer Blends The in-vitro anti-H.pylori activity of LFX and its polymer blends was measured by Mueller-Hinton agar dilution susceptibility tests, in which H.pylori bacterial cells were tested for their ability to produce visible growth on a series of agar plates containing serial dilutions of LFX, Polymer, or 1:1 Blend Figure(4). Results observed showed that LFX has an in-vitro anti- H.pylori activity with MIC of 0.5 µg/ml and more strong activity observed at LFX-SA blend with MIC of 0.25 µg/ml while LFX-EC and LFX-RS100 blends have lower activity with MIC of 1 µg/ml. ( d ) ( c ) Fig. 3. X-ray diffraction patterns of (a) Pure LFX; (b) Polymer alone; (c) LFX-Polymer Physical mixture; (d) Polymer placebo film; (e) LFX-Polymer blend film.