K.V Ratnamala

The objective of the present study is to prepare thermally sintered sustained release tablets of Bosentan monohydrate and to study the effect of sintering conditions on in-vitro dissolution study, hardness and friability. The tablets were prepared by direct compression and wet granulation technique. The prepared tablets were sintered at three different temperatures like 500C, 600C and 700C for three different time periods 1hr, 2hr and 3 hr in a hot air oven. Pre compression and Post compression parameters were performed. Results shown that the release rate of the drug was inversely related to the sintering temperature and the time of sintering. The optimum drug retardation occurred in the tablets sintered at 60 and 700C. The hardness of the sintered tablets was increased with increase in sintering temperature and duration of sintering, whereas friability of tablets was found to be decreased with increasing sintering time. From the FTIR, it was observed that there was no interaction between drug and excipients. Hence, the stearic acid, carnauba wax and EVA 1802 can be used as sintering polymers for controlling the drug release by Thermal sintering technique. F7(6001 hr sintering) showed the maximum sustained release of 99.8%. From the kinetic profile it shows that the drug release followed zero order and Non fickian diffusion with erosion mechanism. From the stability it was observed that the F7(600 1hr sintering) was stable for 3 months under standard conditions. Thus F7(600 1hr sintering) was considered to be the best formulation among all the 7 formulations sintered at various temperatures and various time periods. Hence it shows the suitability of EVA polymer for preparing the Bosentan monohydrate sustained release tablets by Thermal sintering technique. F7( 600C 1 hr sintering) got good the results in Preformulation studies. The angle of repose was 24.45, Hausner’s ratio is 1.08 Compressibility index is 8.81 which indicates the good flowing properties. From the FTIR studies it was observed that there is no interaction between the drug and excipients. As Bosentan is having the high intestinal absorption, by preparing sustained release tablets of Bosentan monohydrate, its bioavailability can be enhanced.  Only the drugs which are having the high melting point are selected for using thermal sintering technique. As Bosentan is having melting point of 1080C, it is used in the preparation of Sustained release tablets of Bosentan monohydrate using Thermal sintering technique.

Sintering is defined as the thermal treatment of a powder or compact at a temperature below the melting point of the main constituent, for the purpose of increasing its bond strength. This concept in pharmaceutical science is relatively new, but research works relating to this process have been growing. Sintering has been described as the mechanism for the strengthening of the mechanical properties of consolidated pharmaceutical powders at elevated temperatures, for solid-bond formation during tablet compression, and for thermal curing of polymer-latex film -Coatings. The changes in the microstructures, Hardness, Friability, Wettability, disintegration time and dissolution rate of tablets stored at elevated temperature were also described as a result of sintering. Controlled release oral dosage forms were developed by sintering the polymer matrix by exposing to temperature above glass transition (Tg) point of the polymer. In the application of thermal sintering technique to the formulation of controlled release dosage form, the main research focus has been on the influence of sintering on the alteration of the microstructures in a polymeric matrix and the release of the active ingredients from the matrix.