Formulation development and pharmacokinetic studies of long acting in situ depot injection of risperidone

Abstract Risperidone is an atypical antipsychotic drug widely prescribed all over the world due to its clinical advantages. The currently available long acting marketed depot formulation of risperidone is a microsphere based preparation using poly-[lactide-co-glycolide] (PLGA) as drug release barrier. It is however, a cold chain product due to thermal instability of PLGA at room temperature. After beginning the depot injection therapy it is administered every two weeks but associated with another drawback of about 3 weeks lag time due to which its tablets are also administered for three weeks so as to attain and maintain therapeutic drug concentration in the body. The present work attempts to develop a long acting depot delivery system of risperidone for once a month administration based on the combination of sucrose acetate isobutyrate and polycaprolactone dissolved in benzyl benzoate to provide an effective drug release barrier for one month without any lag time and which can be stored at room temperature precluding the requirement of cold supply chain. The developed depot formulation showed a sustained in vitro drug release profile with 88.95% cumulative drug release in 30 days with little burst release. The in vivo pharmacokinetic studies of the developed formulation conducted on rats showed attainment of mean peak plasma drug concentration of 459.7 ng/mL in 3 days with a mean residence time of 31.2 days, terminal half-life of 20.6 days, terminal elimination rate constant of 0.0336 per day, and a good in vitro- in vivo correlation.

D-optimal designing and optimization of long acting microsphere-based injectable formulation of aripiprazole.

This work was aimed to design and optimize a long acting microsphere-based injectable formulation of aripiprazole by using D-optimal experimental design methodology. Microspheres were prepared by solvent evaporation method using PLGA and cholesterol as release rate retardant materials. The microspheres were characterized for their encapsulation efficiency, particle size, surface morphology, residual solvent content, and drug release behavior. Contour plots were plotted to study the encapsulation and release behaviour of the drug from the microspheres. Desirability technique was used for the optimization of microsphere formulation composition. By using an optimum blend of drug and cholesterol in the microsphere formulation it was possible to attain a consistent drug release for a period of 14 days. The results have confirmed that the D-optimal experimental design technique can be successfully employed for designing the long acting microsphere dosage form.

Novel approach for delivery of insulin loaded poly(lactide-co-glycolide) nanoparticles using a combination of stabilizers.

Insulin stability during microencapsulation and subsequent release is essential for retaining its biological activity. The successful delivery of insulin relies on the proper selection of stabilizers in addition to other parameters. Attempts were made to address the problem with a few combination of stabilizers for maintaining the integrity of insulin during formulation and delivery. Insulin loaded nanoparticles with different stabilizers such as pluronic F68, trehalose, and sodium bicarbonate were prepared by the double emulsion evaporation method using two different copolymer ratios of poly(DL-lactide-co-glycolide) (50:50 and 85:15). The presence of stabilizers in the nanoparticles resulted in an increase in the particle size but a reduction of encapsulation efficiency. Insulin release rate was comparatively higher for the batches containing stabilizers when compared with controls for both the copolymer ratios. Also the presence of stabilizers resulted in sustained release of insulin resulting in prolonged reduction of blood glucose levels in streptozotocin induced diabetic rats. From the in vitro and in vivo studies, we concluded that a combination of stabilizers results in beneficial effects without compromising the advantages of delivery systems.