Development of a method for environmentally friendly chemical peptide synthesis in water using water-dispersible amino acid nanoparticles

Due to the vast importance of peptides in biological processes, there is an escalating need for synthetic peptides to be used in a wide variety of applications. However, the consumption of organic solvent is extremely large in chemical peptide syntheses because of the multiple condensation steps in organic solvents. That is, the current synthesis method is not environmentally friendly. From the viewpoint of green sustainable chemistry, we focused on developing an organic solvent-free synthetic method using water, an environmentally friendly solvent. Here we described in-water synthesis technology using water-dispersible protected amino acids

Cogrinding as a Tool to Produce Sustained Release Behavior for Theophylline Particles Containing Magnesium Stearate

The aim of the present study was to explore the cogrinding technique as a tool to slow down the drug release from capsule formulations. To this end, the physical mixtures of theophylline–magnesium stearate were prepared and subjected to different milling times (1, 15, 30, 120 min). In order to investigate the effect of magnesium stearate concentration on drug release, various concentrations of magnesium stearate (1%, 3%, 5%, and 10%, w/w) were used. The dissolution rate of the drug from coground samples and physical mixtures were determined at pH 6.5 according to USP. The results showed that all coground formulations showed slower release rates than their physical mixture counterparts. The effect of cogrinding time on the drug release was complex. Cogrinding time had no significant effect on drug release when the amount of magnesium stearate was 1% (w/w). When the amount of magnesium stearate was increased from 1% to 3% and cogrinding time increased from 1 to 5 min, there was a significant reduction in drug release. Beyond 5-min cogrinding, the drug release increased again. For coground samples containing 5% or 10% (w/w) magnesium stearate, generally, the highest drug release was obtained at higher cogrinding time. This was due to a significant increase in surface area of particles available for dissolution as proven by scanning electron microscopy results. Fourier transform infrared and differential scanning calorimetry results ruled out any significant interaction between theophylline and magnesium stearate in solid state

Optimizing the crystal size and habit of β-sitosterol in suspension

The aim of this work was to survey how processing parameters affect the crystal growth of β-sitosterol in suspension. The process variables studied were the cooling temperature, stirring time and stirring rate during recrystallization. In addition, we investigated the effect a commonly used surfactant, polysorbate 80, has on crystal size distribution and the polymorphic form. This study describes the optimization of the crystallization process, with the object of preparing crystals as small as possible. Particle size distribution and habit were analyzed using optical microscopy, and the crystal structure was analyzed using X-ray diffractometry. The cooling temperature had a remarkable influence on the crystal size. Crystals with a median crystal length of ≈23 μm were achieved with a low cooling temperature (<10°C); however, a fairly large number of crystals over 50 μm appeared. Higher cooling temperatures (>30°C) caused notable crystal growth both in length and width. Rapid (250 rpm), continuous stirring until the suspensions had cooled to room temperature created small, less than 50 μm long (median <20 μm), needle-shaped crystals. The addition of surfactant slightly reduced the size of the initially large crystals. Both hemihydrate and monohydrate crystal forms occurred throughout, regardless of the processing parameters. By using an optimized process, it was possible to obtain a microcrystalline suspension, with a smooth texture

Effect of particle size reduction and crystalline form on dissolution behaviour of nimesulide

The objective of this study was to develop and examine innovative and very simple and easily scalable techniques able to improve solubility and/or dissolution rate and thus oral bioavailability of nimesulide. Three different nimesulide batches were obtained by three different laboratory-scale methods: Method A (Batch A) used crystallization by solvent evaporation in a nanospray dryer, Method B (Batches G and GLN) involved cryo-milling, and Method C (Batch Neu) dispersed nimesulide in Neusilin(A (R)) UFL2. All the nimesulide batches were fully characterized for chemical stability, thermal behaviour, physicochemical and micromeritics properties, and intrinsic dissolution and particle dissolution rates. Batch A not only showed a good reduction in particle size but also exhibited a reduced degree of crystallinity by both differential scanning calorimetry and X-ray powder diffractometry, which could explain the increase in intrinsic dissolution rate (IDR) and particle dissolution. Batch GLN showed an acceptable increase in IDR, probably caused by a slight decrease in the degree of crystallinity, and good improvement in dissolution rate due to a certain decrease in particle size. Batches G and native crystals exhibited very close IDRs, while G showed somewhat higher particle dissolution, probably attributed to the particle size reduction. The dispersion of nimesulide in Neusilin UFL2 in a 1:6 drug-polymer ratio made it possible to recover anamorphous powder, as proven by thermal analysis and X-ray powder diffractometry, characterized by pronounced particle size reduction to nanometric dimensions. Both amorphous character and nanometric dimensions could account for the fastest particle dissolution during the first 10 min of the experiment. The stability study conducted according to the International Conference on Harmonization (ICH) confirmed the good chemical and physicochemical stability of all the batches