OPTIMUM CONTENT OF SUPERDISINTEGRANTS FOR PHENYTOIN SODIUM ORALLY DISINTEGRATING TABLETS BY SIMPLEX LATTICE DESIGN

Abstract

Phenytoin sodium orally disintegrating tablets (ODT) were prepared by direct compression.  A statistical experimental design, simplex lattice design, was applied to study the main effects and interactions of the contents of three superdisintegrants,  sodium starch glycolate (Explotab®, SG), crospovidone (Polyplasdone® XL, CP) and croscarmellose sodium (Ac-Di-Sol®, CS) on ODT disintegration time in order to identify the optimum contents of the superdisintegrants which provided the fastest disintegration time.  According to the simplex lattice design; the predetermined various ratios of SG, CP and CS were used as disintegrants resulting in 7 designed tablet formulations. Microcrystalline cellulose (Avicel® PH 102) and spray-dried lactose were employed as direct compressible diluents. Saccharin sodium, magnesium stearate and talcum were used as sweetener, lubricant and glidant, respectively. All the prepared tablet formulations provided disintegration times between 8 to 105 seconds. The tablet formulations containing 0:1:0 SG:CP:CS provided the fastest disintegration times of 8 seconds and met the USP requirement of not less than 85% drug dissolved at the 30th minute time interval. From the obtained tablet properties, the equations representing the relationships between disintegration time and friability as function of the SG, CP and CS ratios utilized in the tablet formulations were computed using the principle of a mixture design, the simplex lattice. From the predicted equations, the two batches of the validated formulation containing 0:0.9:0.1 SG:CP:CS were prepared and tested for tablet disintegration and dissolution. The predicted disintegration time and friability of the validated formulation were 8 seconds and 0.79%, respectively. While the observed disintegration times of 13 and 16 seconds and the observed friability of 0.86% and 0.74% were obtained from the two batches of the validated formulation. However, the ODT containing 0:0.9:0.1 SG:CP:CS failed to meet the USP dissolution requirement despite its fast disintegration time. Therefore, the optimum ratio of the superdisintegrants utilized in preparing the ODT was 0:1:0 SG:CP:CS. A tablet solubilizing agent, sodium lauryl sulfate, was incorporated into the tablet formulation containing 0:1:0 SG:CP:CS to improve the dissolution of the ODT. Inclusion of SLS resulted in the tablet disintegration time of 11 seconds and increased drug dissolution in the initial dissolution stage.