Abstract
According to Biopharmaceutical classification system (BSC), candesartan cilexetil (CC) is a class-II drug which has limited bioavailability mainly due to its low solubility. In order to enhance its solubility, a universal approach of making nanosuspension is been used in the present investigation. High pressure homogenization, controlled precipitation, media milling and high speed homogenization are the various approaches which are most widely used to produce the nanosuspension. Here, nanosuspension is formulated by combination of two approaches; high speed homogenization and media milling to expedite and ease the process. The polymers used to stabilized the nanoparticles were polyvinylpyrrolidone K-30 (PVP K- 30), poloxamer 407, HPMC E 50. To optimize the concentration of the polymer and surfactant the simplex lattice design is used. Various process parameters like homogenization speed, time, media milling cycle, drug to bead ration are optimized by changing one parameter at a time. The nanoparticles produced were of particle size less than 500 nm and were also found to be stable. The saturation solubility was enhaced more than 20 times than the bulk drug. The nanonization of the particles by combination of high speed homogenization and media milling is an effective method of enhancing in vitro dissolution of Candesartan cilexetil. Key word: Media milling, in vitro dissolution, solubility enhancement, nanoparticles, formulation optimization.
Highlights
The Differential scanning calorimetry (DSC) thermograms of bulk CC powder, Poloxamer407, their physical mixture and dried nanosuspension formulation were taken on a Shimadzu DSC-60 differential scanning calorimeter between and 300°C at a heating rate of 10°C/min with nitrogen supplied at 40 ml/min
Acetone and isopropyl alcohol (IPA) were tried in different ratio by keeping all other parameters constant and suitable ratio was selected on the basis of particle size (Table 3)
For the optimization of stirring time of media, milling presuspension obtained from the homogenization cycle was milled for 6, 9 and 12 h and results are displayed in the Table 6, and from the results it was concluded that milling time of 9 h was sufficient to produce the nano suspension
Summary
Poor solubility of a drug is a major concern for the development of new dosage form because about 10% of the present drugs, 40% of the drugs in the pipeline and. Major limitations for media milling is that it usually takes long time (26 to h) in converting drug particles into the nano stage when the speed is mediocre, and high pressure homogenization requires very costly instrumentation. Another method is to use high speed homogenizer instead to high pressure because it is less costly and easier than high pressure homogenizer but it can hardly give the particle size below 600 nm, which will not be sufficient to take full advantage of nano particles. Here nanoparticles of the candesartan were prepared to increase its solubility and dissolution velocity
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