ESTIMATION OF THE DRUG-DRUG AND DRUG-POLYMER OPHTHALMIC COMPLEX AT STOICHIOMETRY BY TERNARY PHASE BEHAVIOUR Original Article BHUSHAN S BHOYAR 1* , ARUN T PATIL 1 1 Received: 11 Feb 2015 Revised and Accepted: 10 Mar 2015 Department of Pharmaceutical sciences, RTM Nagpur University, Nagpur Email: bhushanbhoyar@rediffmail.com ABSTRACT Objective: The study focus on the drug-drug and drug-polymer interaction and their estimation at stoichiometry when such systems were formed. In this discovery we tried to make use of the latest research and novel concepts to explore the drug-polymer-polymer Ionic ternary Interaction Methods: Partial ternary phase diagrams were constructed and the stoichiometry of the ciprofloxacin/anionic polymer interaction was assessed in distilled water by means of dialysis equilibrium. The polymers were completely hydrated in distilled water by gentle stirring at room temperature and studied for viscosity and turbidimetric measurements. Results: Comparing the partial ternary phase diagrams of the different anionic to each other. PAA exhibited the largest gel area even with low polymer content. The anionic polymers HA and PAA showed good capability to interact with the drug giving soluble drug/polymer complexes; moreover they were able to form polymer/polymer complexes with Poloxamer and HCS, with a stoichiometry depending on the polymers involved. Conclusion: From the results of the present study, it can be concluded that formulations were made isotonic and favours corneal permeation of both the drug. Ocular Irritancy denotes formulations were quite stable & useful in novel format of sol-gel transformations. Keywords: Cationic, Anionic, Cul-de-sac, Poloxamer. INTRODUCTION The ophthalmic products should always been considered for the critical bioavailability and ocular retention. The critical parameters in ocular dosage form depend upon the interaction between drug and polymer. Extensive literature is available on drug-drug-polymer interaction [1]. Yet most data were not capable of describing things efficiently. In the present study, we tried to elaborate drug-drug- polymer interaction at stoichiometric concentration by ternary phase behaviour study. Blinking, baseline and reflex lachrymation, and drainage remove rapidly foreign substances, including drugs, from the surface of the eye [2, 3]. To enhance the amount of active substance reaching the target tissue or exerting a local effect in the cul-de-sac, the residence time of the drug in the tear film should be lengthened. The use of a water-soluble polymer to enhance the contact time and possibly also the penetration of the drug was previously proposed by different authors. Where very promising results and improved bioavailability were observed in animal studies, only a small increase in precorneal residence time was obtained in humans [4]. The most useful an alternative approach has been the application of in situ gelling systems or phase transition systems, which are instilled in a liquid form and shift to a gel or solid phase in the cul-de-sac. The phase transition is triggered by the pH of the tears, the temperature at the eye surface or the electrolytes present in the tear film. A further approach to optimize the ocular dosage form was the implementation of the mucoadhesive concept. Interactions of suitable natural and synthetic polymers with mucin were evaluated. Due to interactions with the mucus layer or the eye tissues, an increase in the precorneal residence time of the preparation was observed [5]. The present study will focus on development of the formulation of Ophthalmic Gel and Solution. In this discovery, we tried to make use of the latest research and novel concepts to explore the drug-polymer-polymer Ionic ternary Interaction. MATERIALS AND METHODS Poloxamer P407 was obtained from BASF Corp. (Ludwigshafen, Germany); Ciprofloxacin HCl was kindly gifted from Inventia healthcare Pvt. Ltd. (INDIA). Chitosan and PVA were purchased from MERK. Triethanolamine, Benzalkonium chlorides were obtained from Research lab fine chem. industries (INDIA). Poloxamer (P), Polyacrylic acid (PAA), Polyvinyl alcohol (PVA) was obtained from laboratory UDPS, Nagpur University. Effect of ionic interaction on phase behaviour Constructions of ternary phase diagrams Partial ternary phase diagrams were constructed for (≤2% (w/v) of polymeric solution, anion and cation. The effect of cationic and anionic interaction that is feasible for the sol to gel transition was investigated. Polymers were dissolved in water & then, the appropriate amount of a 1% cationic & anionic solution was added in stoichiometry and left overnight to equilibrate. Formulations were assessed the following day in terms of their visual appearance and flow (by tilting the vial to an angle of 90ñ), and were classified as solutions, viscous solutions or gels. Estimation of the drug–polymer complex The stoichiometry of the ciprofloxacin/anionic polymer interaction was assessed in distilled water by means of dialysis equilibrium. Dialysis bags were filled with 10 ml of a 0.5% w/v anionic polymer solution. The bags were closed and put in 40 ml of ciprofloxacin solution where they were maintained under agitation at 37 °C until equilibrium was reached (24h). The dialysis membrane did not allow the polymer to get out but allowed the ciprofloxacin to diffuse into and eventually to interact with the polymer. Different initial ciprofloxacin concentrations outside the dialysis bags were tested ranging between 0.5 and 5 µM. After the equilibrium was attained, the final ciprofloxacin concentration outside the dialysis bag was assayed by means of a spectrophotometrically detection at 274.2 nm specific wavelengths. The data were interpreted & the procedures were reproduced with ketorolac tromethamine [6, 7]. Estimation of the polymer–polymer complex viscosimetric measurements The polymers were completely hydrated in distilled water by gentle stirring at room temperature. Mixtures (30 ml) containing a fixed amount of HCS (0.5% w/w) and increasing amounts of the anionic polymers (HA and PAA) were also prepared at different ratios ranging from 1/0.25 to 1/2. The interaction products were removed by means of the centrifugation at 2000 rpm for 10 min and the viscosity of the supernatants was measured. The polymer/polymer ratio where a minimum of viscosity was observed could be considered the International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Issue 5, 2015 Innovare Academic Sciences