Aim and Objective: The primary aim of the present investigation was to adopt the concept of quality by design (QbD) for developing Febuxostat matrix tablets containing a novel combination of polyethylene oxide (PEO), pre-gelatinized starch (PGS) and lactose for obtaining biphasic drug release. Experimental work: Febuxostat-containing matrix tablets were prepared by direct compression using 32 full factorial designs. The tablets were prepared with varying amounts of PEO WSR 301 to PGS and lactose to obtain the desired release pattern. The chosen responses were cumulative % drug released at 1, 6 and 12 hours. The evaluation of tablets was done for pre and post-compressional parameters. Compared with the marketed tablet, the optimized formulations were selected based on in vitro drug release. Dose dumping was checked in the dissolution medium containing up to 40% alcohol. Result and discussion: The results of the dissolution study indicated that the batch containing a 1:1 ratio of PEO WSR 301 and PGS (15 mg each) and 20 mg of Lactose showed fast initial drug release to imitate the pharmacological action followed by sustained drug release effect. The use of Lactose facilitated immediate drug release, while PEO WSR 301 and PGS exhibited the opposite effect on cumulative drug release. The results of the 32 Factorial design revealed that the concentration of Lactose is a critical parameter. Dose dumping was not observed in the alcoholic dissolution medium. Kinetic equations were fitted to the dissolution data after 1 hour of the dissolution study. Conclusion: The type (soluble or swellable) and the concentration of excipients (low or high) dictate the tablets' drug release. The study's outcome revealed that the most critical material attribute is the amount of lactose. The novel combination of PEO, PGS and lactose can bypass existing patents and give more industrial applicability.

This study was aimed to utilize the Moisture Activated Dry Granulation (MADG) technique to formulate Bicalutamide tablet and identify critical factors influencing its dissolution. The Bicalutamide inclusion complex was formed using the kneading method. Aeroperl 300 was selected as an adsorbent, polyvinylpyrrolidone (PVP) K30 as a binder, Microcrystalline Cellulose (MCC) and Lactose Monohydrate (LMH) in1:1 ratio as fillers. Croscarmellose sodium (CCS) and neusilin were used as disintegrating agents, as they did not affect the disintegration time when hardness and compression force increased. Box Behnken experimental design was used to optimize formulations and was evaluated for pre and post-compression parameters. The optimized formulation was compared with the marketed and wet granulation formulation. In addition, the short term stability testing of the optimized batch was performed. The optimized inclusioncomplex of hydroxypropyl beta-cyclodextrin (HP-ß-CD) was selected based on a phase solubility study in 1:1 ratio with drug toimprove solubility. The optimized batch was prepared by MADG at granulator speed of 540rpm, using 4.30 % PVPK30, and 1.5 % Aeroperl 300. It showed a disintegration time of 208.33 sec.Percentage drug release was 95.02 % in 30 mins, and hardness 5.4 kg/cm2. The stability study results confirmed the stability of the tablets. The Bicalutamide tablet was successfully formulated using the MADG technique. The parameters affecting the in-vitro dissolution were identified and optimized, leading to better bioavailability. Keywords: Bicalutamide, Moisture Activated Dry Granulation technology (MADG), hydroxypropyl beta-cyclodextrin (HP-β-CD), Box Behnken design (BBD), Croscarmellose sodium

The present study was aimed to apply quality by design to develop stable and flexible pediatric granules of BCS class II drug Cefiximeto improve dissolution profile using Soluplus®. Thegranules were prepared by employing the wet granulation technique. The concentration of Soluplus®(X1), Croscarmellose sodium(X2), Sodium bicarbonate(X3) were identified as critical material attributes(CMA). The critical quality attribute (CQA) are percentage drug release in 20 minutes (Y1) and dispersion time (Y2). All 17 batches were evaluated for micromeritics properties, drug content, particle size distribution, dispersion time, granules' strength/friability, In vitro drug release, comparison with marketed product and stability study. All 17 batches from the Box Behnken showed all the test results values within limits, indicating that the prepared granules were of standard quality. The optimized batch of granules showed 94.45±0.26% drug release in 20min, while the dispersion time was 90.85±0.04 sec and the similarity factor (f2) was 56.39 to marketed product (ZIPRAX). In addition, the optimized batch exhibited no significant change in drug content, dispersion time, in vitro drug release after storage at 40°C ±2°C and 75% RH ± 5% RH for one month. The formulated granules showed better drug release and dispersion time. The granules can be reconstituted with water to prepare dispersion of the drug just before use to improve compliance of paediatric patients. Keywords: Cefixime, granules, Quality by design, Box Behnken design, Soluplus®, Design space