Abstract
Objective: Rizatriptan benzoate (RB) is a new generation anti-migraine drug. After oral administration, the peak plasma concentrations (tmax) occur in about 1 to 2.5 hrs depending on the formulation and the bioavailability which is about 40 to 45%. Food may delay the tmax by about 1 hour. The aim of this work was to design and develop fast dissolving tablets of RB to improve the bioavailability and patient compliance applying the Mixture Experimental Design. Methods: Twenty formulations were prepared by direct compression each containing 14.53 mg of RB equivalent to 10 mg Rizatriptan with different proportions of superdisintegrants (X1-X3) according to the experimental design. The independent factors selected were the percentages of: Croscarmellose sodium (X1), Explotab (X2) and Polyplasdone XL 10 (X3). The dependent variables investigated were: hardness (Y1), disintegration time (Y2) and cumulative % drug release after 10 minutes (Y3). The formulations were evaluated for the pre-compression parameters to assess the powder compressibility and flowability (bulk and tapped density, Hausner’s ratio, Carr’s index and angle of repose) as well as the post-compression parameters (weight variation, friability, hardness, disintegration time, wetting time, water absorption ratio, drug content and in-vitro drug release). The optimized formulation was prepared and evaluated in the same manner. Results: All the evaluated parameters, either for powder blend or for the compressed tablets, were within the acceptable limits. The values of dependent variables ranged between 3.13-3.68 kg/cm2; 12.23-21.81 sec; and 94.44-99.83% for Y1, Y2 and Y3 respectively. Polynomial regression equations for the variables (Y1-Y3) were generated and the quantitative effects of X1-X3 at different levels on Y1-Y3 could be predicted. Surface response and contour plots were plotted. The optimal ratios of different disintegrants were used to prepare the optimized formulation. The difference between the predicted and the observed data for the optimized formula were minimal. Conclusions: The use of direct compression technique and the mixture experimental design succeeded to produce fast dissolving tablets of RB with optimal hardness, minimal disintegration time and maximal in vitro drug release. The quantitative effects of the selected factors tested on the different variables were explored. Based on the obtained results, fast dissolving tablets of RB could be a potential dosage form for quick relieve of migraine patients.
Highlights
The oral cavity is still the attractive site for drug administration because of ease and versatility of use
Known as fast melting, fast dispersing, rapid dissolve, rapid melt, and quick disintegrating tablets, disintegrate in the mouth without chewing and there is no need for water to facilitate swallowing (Chopda et al, 2014)
All fast dissolving tablets approved by FDA are classified as orally disintegrating tablets
Summary
The oral cavity is still the attractive site for drug administration because of ease and versatility of use. The European Pharmacopeia adopted the term orodispersible tablet for a tablet that disperses or disintegrates in the mouth in less than 3 minutes before swallowing. The most common preparation methods are molding, lyophilization, direct compression, cotton-candy, spray drying, and sublimation ((Parakh and Gothoskar, 2003; Evren et al, 2014) Each one of these has advantages and disadvantages. Direct compression represents one of the techniques that require the incorporation of superdisintegrants into the formulation and the use of highly water soluble excipients to achieve fast tablet disintegration (Indurwade, 2002). This technique does not require the use of water or heat during the formulation procedure and is the ideal method for moisture and heat-labile drugs. DOE was to generate the optimized formulation which was prepared and characterized in the same manner
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