Original Article STUDY THE SUSTAIN RELEASE EFFECT OF DIFFERENT POLYMERS USED IN THE FORMULATION OF ASPIRIN-ROSUVASTATIN TABLETS OMAR S. SALIH *1 1 Received: 30 Aug 2015 Revised and Accepted: 27 Oct 2015 Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Iraq Email: omarpharma2007@gmail.com ABSTRACT Objective: Low permeability of rosuvastatin calcium faces a problem of low bioavailability (absolute bioavailability 20%) as its permeation is the rate limiting factor. Rosuvastatin calcium is a selective competitive inhibitor of HMG-CoA reductase and it lowers plasma cholesterol level. Aspirin is an anti-platelet agent with half-life of 6-7 h. Frequency of dosing of both drugs is high to maintain the desired plasma drug concentration so it is selected to formulate a sustained release tablet of aspirin and rosuvastatin calcium, which release the drug in a sustained manner over a period of time by using various polymers and study the effect of polymers on the release pattern of both drugs. This approach will also enhance the residence time of rosuvastatin calcium at the absorption site and enhance permeation by the effect of the polymers used and this in turn will enhance bioavailability. Methods: Tablets contain aspirin plus rosuvastatin calcium were prepared by direct compression method. The sustained release of the tablets was obtained by using different polymers (xanthan gum, microcrystalline cellulose, HPMC K4M and chitosan) incorporated in the tablet and responsible for the release of both drugs from each tablet. Tablets were evaluated for weight variation, drug content, friability, hardness and thickness for all batches (F1 to F12). In-vitro dissolution was studied for all batches (F1 to F12) according to the type and ratio of each polymer used within these formulas i.e. (10 mg, 20 mg and 30 mg) respectively. Results: The release of aspirin and rosuvastatin calcium from sustained release tablets varied according to the type and amount (ratio) of each polymer used. After the 7 h release study; (F1, F2, F3) that uses xanthan gum as the sustain release polymer showed the most sustained formulations than other polymers. The sustained release of drugs from tablet enhanced by increasing the amount of polymer, so F3 for example, which contain 30 mg xanthan gum had most sustained release than F1 and F2 which contain (10 mg and 20 mg) of the polymer respectively, this due to polymer related viscosity, swelling and binding mechanisms. Conclusion: Using suitable polymer for sustained release will enhance the pharmacokinetics and efficacy of drugs and increase patient complains about combination therapy. Keywords: Rosuvastatin calcium, Hyperlipidemia, Aspirin, Sustain release tablet, Polymers INTRODUCTION The majority of the discovered and existing drugs administered orally may face bioavailability problems because of many reasons such as poor dissolution, unpredicted absorption and inter-intra- subject variation [1]. Developed and developing countries move towards a combination therapy used for the treatment of diseases requiring long-term therapy. Combination therapy has various advantages such as less dose-dependent side effects. Further, low dose combination of two different drugs decreases the clinical and metabolic side effects that occur with a maximal dosage of an individual component of the combined tablet and so dose of one component can be decreased [2]. Oral sustained release dosage forms were the most commonly formulated and offer highest interesting in the area of novel drug delivery systems. Prolonging the gastric retention is desirable for achieving the therapeutic benefit of drugs that are absorbed in the stomach and small intestine or drugs are less soluble in or degraded by high pH they encounter at the distal part of the gastrointestinal tract (GIT). Sustain release and gastric retention mechanisms had the benefit of such drugs by improving their bioavailability, therapeutic efficacy and reduction of dose. These mechanisms had various pharmacokinetics advantages like maintenance of constant therapeutic levels over a prolonged period of time and so decrease in fluctuations in therapeutic levels [3]. The goal in designing a sustained delivery system to reduce the number of dosing and increase the effectiveness of the drugs by targeting at the site of action so reducing the dose required by providing this uniform drug delivery system. The sustained release mechanism is defined as a dosage form that release one or more drugs continuously in a predetermined pattern for a fixed period of time, either systemic or local [4]. In this approach drugs rosuvastatin calcium (RSC) and aspirin used to enhance combination therapy for patients with cardiovascular diseases and hypercholesterolemia and enhance the bioavailability of the drugs by sustaining release mechanism as compared to the single plane tablet for each one in the market. Polymers and their blends are used in the formulations to achieve sustained drug release from the dosage form. Most thoroughly investigated and used synthetic agents are hydroxyl propyl methyl cellulose (HPMC) and sodium carboxymethyl cellulose (NaCMC) [1]. The main adverse effects associated with Aspirin (acetylsalicylic acid) are the gastrointestinal disturbances and ulcer. Sustained release tablets of aspirin provide a more constant plasma drug concentrations with the less frequent administration, also could help lower the side effects to some degree. This could prolong its safe administration and improve patient compliance [5]. Unlike other statins, rosuvastatin calcium is hydrophilic. Low solubility and bioavailability of rosuvastatin calcium when taken orally as a tablet dosage form make the pharmacist develop a new dosage form to enhance dissolution and permeation and hence bioavailability of the drug when taken orally, so sustain release approach is used to enhance bioavailability of rosuvastatin calcium [6]. MATERIALS AND METHODS Materials Materials were used: Rosuvastatin calcium (Atra Pharmaceuticals, India), Aspirin (Samara drug industry, Iraq), Xanthan gum (HIMEDIA Laboratories, India), Microcrystalline cellulose (MCC) (Avecil pH 102) (Sigma Aldrich CO, USA), hydroxyl propyl methyl cellulose (HPMC) K4M (HIMEDIA Laboratories, India),Chitosan (HIMEDIA International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Issue 12, 2015 Innovare Academic Sciences