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The objective of this study was to investigate the sustained release of a hydrophilic drug, montelukast (MK), from two biodegradable polymeric drug delivery systems, in situ implant (ISI) and in situ microparticles (ISM). N-Methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO), triacetin, and ethyl acetate were selected as solvents. The release of 10% (w/v) MK from both systems containing poly-lactic-co-glycolic acid (PLGA) as the biodegradable polymer was compared. Upon contact with the aqueous medium, the PLGA in ISI and ISM systems solidified resulting in implants and microparticles, respectively. The in vitro drug release from the ISI system showed marked difference from miscible solvents (NMP and DMSO) than the partially miscible ones (triacetin and ethyl acetate), and the drug release decreased with increased PLGA concentration. In the ISM system, the initial in vitro drug release decreased with decreased ratio of polymer phase to external oil phase. In vivo studies in rats showed that ISM had slower drug release than the drug release from ISI. Also, the ISM system when compared to ISI system had significantly reduced initial burst effect. In vitro as well as the in vivo studies for both ISI and ISM systems showed sustained release of MK. The ISM system is suitable for sustained release of MK over 4-week period with a lower initial burst compared to the ISI system. Stability studies of the ISI and ISM formulations showed that MK is stable in the formulations stored at 4°C for more than 2 years.

Meloxicam in situ implant may provide long-term management of inflammatory conditions with improved patient compliance and better therapeutic index.

The aim of this study was to systematically obtain a model of factors that would yield an optimized self-nanoemulsified capsule dosage form (SNCDF) of a highly lipophilic model compound, Coenzyme Q10 (CoQ). Independent variables such as amount of R-(+)-limonene (X 1 ), surfactant (X 2 ), and cosurfactant (X 3 ), were optimized using a 3-factor, 3-level Box-Behnken statistical design. The dependent variables selected were cumulative percentage of drug released after 5 minutes (Y 1 ) with constraints on drug release in 15 minutes (Y 2 ), turbidity (Y 3 ), particle size (Y 4 ), and zeta potential (Y 5 ). A mathematical relationship obtained, Y 1 = 78.503 + 6.058X 1 + 13.738X 2 + 5.986X 3 -25.831X 1 2 + 9.12X 1 X 2 -26.03 X 1 X 3 -38.67 X 2 2 +11.02X 2 X 3 -15.55 X 3 3 (r 2 = 0.97), explained the main and quadratic effects, and the interaction of factors that affected the drug release. Response surface methodology (RSM) predicted the levels of factors X 1 , X 2 , and X 3 (0.0344, 0.216, and 0.240, respectively), for a maximized response of Y 1 with constraints of >90% release on Y 2 . The observed and predicted values of Y 1 were in close agreement. In conclusion, the Box-Behnken experimental design allowed us to obtain SNCDF with rapid (>90%) drug release within 5 minutes with desirable properties of low turbidity and particle size.