In vitro and in vivo evaluation of nimesulide lyophilized orally disintegrating tablets

Development of a lyophilized orally disintegrating tablet (ODT) that enhanced the in vitro dissolution and in vivo absorption of nimesulide (NM), a drug with poor solubility and poor bioavailability, is presented. The ODTs were prepared by freeze-drying an aqueous dispersion of NM containing a matrix former, a sugar alcohol, and a collapse protectant. In addition, different disintegration accelerators were tested. The influence of formulation parameters on the disintegration time and in vitro dissolution of NM from ODTs along with other tablet characteristics was investigated. Results obtained from disintegration and dissolution studies showed that lyophilized ODTs disintegrated within few seconds and showed significantly faster dissolution rate of NM compared to the plain powder drug and NM in commercially available immediate release tablet Sulide®. The ODTs were also examined using differential scanning calorimetry, X-ray diffraction, and scanning electron microscope. Stability results, after 12-month storage of selected ODTs at 25 °C and 60% relative humidity, were satisfactory. The extent of absorption of NM from a selected ODT when compared to an conventional immediate release tablet as a reference after administration of 100 mg oral dose of NM was determined in healthy subjects using a randomized crossover design. In this study, the rate of absorption of NM from ODT was faster than that from the reference tablet, had a significantly higher (p = 0.012) peak plasma concentration, and shortened time to Cmax by 1 h (p = 0.029). The extent of absorption expressed by AUC was 62% larger when compared to the commercially available tablet.