## 1 Introduction  
According to the World Health Organization (WHO), ischemic heart disease and stroke is the leading cause of adult-acquired disability and death worldwide [1]. Several antiplatelet drugs with different mechanisms of action are currently available for secondary prevention of cardiovascular events such as ischemic stroke, myocardial infarction, and peripheral vascular disease. The most used oral antiplatelet drugs are acetylsalicylic acid, clopidogrel, dipyridamole, prasugrel, epoprostenol, and streptokinase. A combination of clopidogrel with acetylsalicylic acid may be substantially more effective than either drug alone [2; 3; 4]. Dual antiplatelet therapy appears to be safer and more effective in reducing stroke recurrence and combined vascular events in patients with acute ischemic stroke or transient ischemic attack, as compared with monotherapy [3; 5]. In a large, randomized, blind, international trial (CURE), the safety and efficacy of the combination of clopidogrel and acetylsalicylic acid in patients with acute coronary syndromes were assessed. This study demonstrated that clopidogrel used with acetylsalicylic acid reduces death or myocardial infarction in patients undergoing intracoronary stent implantation by 77%, compared with acetylsalicylic acid alone [6]. Patient compliance has also shown improvement when a dosage form combining two active pharmaceutical ingredients (APIs) was used [7]. On the market, combination therapy that contains clopidogrel bisulfite and acetylsalicylic acid is available in the form of film-coated tablets. Acetylsalicylic acid (ASA) (2-acetoxybenzoic acid) is a nonsteroidal anti-inflammatory drug and platelet aggregation inhibitor (Figure 1a). The mechanism of action is that of a cyclooxygenaseinase inhibitor [8]. Acetylsalicylic acid is practically insoluble in water, and freely soluble in ethanol 96% _v/v_[9]. Clopidogrel bisulfite (CB) (S-methyl 2-(2-chlorophenylenyl-6,7-dihydrotion [3,2-c]pyridine-5(4)-acetatesulfate) is a thienopirdine antiplatelet drug (Figure 1b). It is an antithrombotic agent that inhibits adenosine diphosphate-mediated platelet aggregation by selectively and irreversibly blocking platelet purinergic P2Y12 receptors [10; 11]. Clopidogrel bisulfite is practically insoluble in water at neutral pH, but freely soluble at pH 1. It also dissolves freely in methanol, sparingly in methylene chloride, and is practically insoluble in ethyl ether [11]. Development of formulation and validation of the dissolution method for poorly water soluble drugs has been a challenge in the pharmaceutical industry and for scientists, especially for drugs which belong to Biopharmaceutical Classification System (BCS) II or IV groups, like acetylsalicylic acid and clopidogrel bisulfite, with low solubility and/or permeability. Low solubility and dissolution rate are usually a limiting factor for oral drug absorption of these substances and consequently affect the bioavailability and therapeutic efficacy of the drug [12; 13]. Formulations of solid dispersions (SD) were often used to increase the solubility and dissolution rate of low solubility drugs [12; 14; 15; 16; 17]. A solid dispersion is a dispersion of one or more active ingredients in a hydrophilic inert carrier matrix at solid state. Two basic procedures used to prepare solid dispersions are solvent evaporation and melting methods [15; 16; 18; 19]. There are a number of HPLC methods available in the literature for the estimation of ASA and CB alone, and only a few methods are reported for simultaneous determination of both APIs [20; 21; 22; 23; 24; 25; 26], but there is no method reported for simultaneous estimation of ASA and CB after release from solid dispersion. This method was required primarily due to the application of excipients in solid dispersions  
Figure 1: Chemical structure of acetylsalicylic acid (**a**) and clopidogrel (**b**). not used in previous studies to achieve adequate selectivity and also to shorten the retention time compared to the mentioned investigations.