REVIEW: AN EFFORTS TO INCREASE THE SOLUBILITY AND DISSOLUTION OF ACTIVE PHARMACEUTICAL INGREDIENTS

The most significant aspect of a drug's physicochemical nature is its solubility. If the medicine is in a dissolved form, it can dissolve and enter the membrane, resulting in a therapeutic effect. The pharmacokinetic phase of the drug in the body, which includes absorption, distribution, metabolism, and excretion, will be correlated with solubility. Some medications, however, have a low solubility. To obtain a therapeutic impact, an effort must be made to increase the drug's solubility. Based on the literature research, the goal of this paper is to explain approaches that can be utilized to improve solubility. In general, physical, chemical, and micelle formation efforts can all be used it to enhance solubility. Particle size reduction, crystal shape modification, and the utilization of matrices in the disperse phase are examples of physical alterations. pH adjustment, buffering, salt formation, complexation, and derivatization all are examples of chemical alterations. The employment of supercritical processes in solutions and also excipients such as surfactants, cosolvents, stabilizing solutions, and others are examples of how micelle formation can be modified.

Applying Box–Behnken Design for Formulation and Optimization of PLGA-Coffee Nanoparticles and Detecting Enhanced Antioxidant and Anticancer Activities

In an attempt to prove biological activity enhancement upon particle size reduction to the nanoscale, coffee (Cf) was chosen to be formulated into poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) using the single emulsion-solvent evaporation (SE-SE) method via Box–Behnken Design (BBD) to study the impact of certain process and formulation parameters on the particle size and size homogeneity, surface stability and encapsulation efficiency (EE%). The coffee-loaded PLGA (PLGA-Cf) NPs were characterized by different methods to aid in selecting the optimum formulation conditions. The desirable physicochemical characteristics involved small particle sizes with an average of 318.60 ± 5.65 nm, uniformly distributed within a narrow range (PDI of 0.074 ± 0.015), with considerable stability (Zeta Potential of −20.50 ± 0.52 mV) and the highest EE% (85.92 ± 4.01%). The antioxidant and anticancer activities of plain PLGA NPs, pure Cf and the optimum PLGA-Cf NPs, were evaluated using 2,2-Diphenyl-1-picryl-hydrazyl (DPPH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. As a result of nano-encapsulation, antioxidant activity was enhanced by 26.5%. Encapsulated Cf showed higher anticancer potency than pure Cf against different cancerous cell lines with an increase of 86.78%, 78.17%, 85.84% and 84.84% against MCF-7, A-549, HeLa and HepG-2, respectively. The in vitro release followed the Weibull release model with slow and biphasic release profile in both tested pH media, 7.4 and 5.5.

Preparation and Characterization of Fenofibrate Microparticles with Surface-Active Additives: Application of a Supercritical Fluid-Assisted Spray-Drying Process

In this study, supercritical fluid-assisted spray-drying (SA-SD) was applied to achieve the micronization of fenofibrate particles possessing surface-active additives, such as d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), sucrose mono palmitate (Sucroester 15), and polyoxyethylene 52 stearate (Myrj 52), to improve the pharmacokinetic and pharmacodynamic properties of fenofibrate. For comparison, the same formulation was prepared using a spray-drying (SD) process, and then both methods were compared. The SA-SD process resulted in a significantly smaller mean particle size (approximately 2 μm) compared to that of unprocessed fenofibrate (approximately 20 μm) and SD-processed particles (approximately 40 μm). There was no significant difference in the effect on the particle size reduction among the selected surface-active additives. The microcomposite particles prepared with surface-active additives using SA-SD exhibited remarkable enhancement in their dissolution rate due to the synergistic effect of comparably moderate wettability improvement and significant particle size reduction. In contrast, the SD samples with the surface-active additives exhibited a decrease in dissolution rate compared to that of the unprocessed fenofibrate due to the absence of particle size reduction, although wettability was greatly improved. The results of zeta potential and XPS analyses indicated that the surface-active additive coverage on the surface layer of the SD-processed particles with a better wettability was higher than that of the SA-SD-processed composite particles. Additionally, after rapid depletion of hydrophilic additives that were excessively distributed on the surfaces of SD-processed particles, the creation of a surface layer rich in poorly water-soluble fenofibrate resulted in a decrease in the dissolution rate. In contrast, the surface-active molecules were dispersed homogeneously throughout the particle matrix in the SA-SD-processed microparticles. Furthermore, improved pharmacokinetic and pharmacodynamic characteristics were observed for the SA-SD-processed fenofibrate microparticles compared to those for the SD-processed fenofibrate particles. Therefore, the SA-SD process incorporating surface-active additives can efficiently micronize poorly water-soluble drugs and optimize their physicochemical and biopharmaceutical characteristics.

Physicochemical Properties of Zinc and Lactose in Solid Mixtures: Influence of Trituration Process

Background Recent experimental results supporting the dynamization process show modification in the characteristics of solid mixtures. Objective The present work aims to evaluate the physicochemical properties of metallic zinc and lactose, evidencing the interactions between all chemical components presented in dynamized solid mixtures by analytical techniques. Methods Mixtures of zinc and lactose (1:9 w/w) were successively triturated at the same proportion according to the Brazilian Homeopathic Pharmacopoeia, receiving the designation of 10−1 – 10−6 (1dH – 6dH). All samples were submitted to the following characterization techniques: Atomic Absorption Spectrometry (AAS), Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), and Raman Spectroscopy (RS). Results AAS results detected 97.0% of zinc in the raw material, and the triturated zinc lactose system (ZnMet) presented mean values similar to those expected for the physical mixtures: i.e., 9.94%, 1.23%, and 0.11% in the three first proportions (10−1, 10−2, 10−3), respectively. SEM images showed particle size reduction due to the trituration process. The XRD assays of ZnMet 10−3 and 10−6 indicated peak changes at 12.3° and 43.26°, probably associated with modifications of inter-atomic crystalline spacing. The thermal analysis results of dynamized samples suggest modifications in the chemical interaction between zinc and lactose induced by the physical forces applied. RS experiments showed variation in vibration frequencies due to the dynamization procedure, in which marked ZnMet 10−6 spectral modifications were detected at 357, 477, 1086 and 1142 cm−1, and in the wavelength range 860–920 cm−1. Conclusion These results highlight the importance of applying suitable characterization methods to improve our understanding of the properties of homeopathic solid mixtures, whereas the uses of sensitive tools evidence the influence of trituration on the crystalline properties and in the enthalpy variation of dynamized samples.

A Review of the Milestones Reached by the Attainable Region Optimisation Technique in Particle Size Reduction

The attainable region (AR) is an optimization method adopted for use in comminution to achieve different objective functions, which all converge to optimising the production of the desired particle size distributions for downstream processes. The technique has so far mostly been used to optimise the breakage of particles in tumbling mills. It achieved the desired purpose by unveiling all possible outcomes derived from a combination of operational parameters that are bound by trajectories showing the limitations of a system. The technique has given the scientific community lenses to see the behaviour of different parameters in ball mills otherwise known as the black boxes due to their concealing nature. Since its inception, the AR technique has been applied to data obtained from the laboratory tests and simulated industrial mills and the results sometimes contradict or confirm the conventional milling practices in the industry. This makes the already conservative mining industry sceptical about its adoption. This review thus assesses the milestone covered as far as the AR development in comminution is concerned. It also helps to clarify the sources of the discrepancies between the AR results and the conventional knowledge concerning the optimisation of ball mill operational parameters.

Impact of particle size reduction on high gravity enzymatic hydrolysis of steam-exploded wheat straw

Economically feasible bioethanol production from lignocellulosic biomass requires solid loadings ≥ 15% dry matter (DM, w/w). However, increased solid loadings can lead to process difficulties, which are characterized by high apparent slurry viscosity, insufficient substrate mixing and limited water availability, resulting in reduced final glucose yields. To overcome these limitations, this study focused on enzymatic hydrolysis of 10–35% DM solid loadings with steam-exploded wheat straw in two different particle sizes. At solid loadings of 20 and 25% DM small particle size of ≤ 2.5 mm yielded 16.9 ± 1.1% and 10.2 ± 1.4% increased final glucose concentrations compared to large particle size of 30 ± 20 mm. Small particle size also positively influenced slurry viscosity and, therefore, miscibility. As a key finding of this investigation, high gravity enzymatic hydrolysis with solid loadings of 30–35% DM was indeed successfully employed when wheat straw was applied in small particle size. Here, the highest final glucose yield was achieved with 127.9 ± 4.9 g L−1 at 35% DM solid loading. An increase in the solid loading from 10 to 35% DM in small particle size experiments resulted in a 460% increase in the final glucose concentration.

Formulation and Evaluation of Nanosuspension as an Alternative Approach for Solubility Enhancement of Simvastatin

Solubility is an essential factor for drug effectiveness. Simvastatin is poorly water-soluble drug and its bioavailability is very low. Nanosuspension is one of those approach which can tremendously enhance the effective surface area of drug particles by reducing the particle size and there by increases the rate of dissolution and hence improve bioavailability. The main purpose of the present investigation was to increase the saturation solubility of simvastatin by preparation of nanosuspension. Nanosuspension of simvastatin were prepared by nanoprecipitation method using hydroxypropyl cellulose as stabilizer and sodium lauryl sulphate as surfactant. Prepared nanosuspension was evaluated for its particle size, total drug content, entrapment efficiency and saturation solubility study. On the basis of the evaluation, the best batch F8 formulation demonstrated highest drug content and entrapment efficiency with average particle size of 0.004µm. The saturation solubility studies show the solubility of the prepared nanosuspension has increased as compared to the pure drug due to the particle size reduction. The nanosuspension of simvastatin could be successfully prepared and can be concluded that the nanosuspension formulation is a promising approach to enhance the solubility. The nanoprecipitation is a simple and effective method to produce nano sized particles of poorly water-soluble drugs with enhance solubility.

“FORMULATION DEVELOPMENT AND SOLUBILITY ENHANCEMENT OF ROSUVASTATIN CALCIUM BY USING HYDROPHILIC POLYMERS AND SOLID DISPERSION METHOD”

Objective: Preparation of Rosuvastatin Calcium by Using Hydrophilic Polymers and Solid Dispersion Method, Rosuvastatin calcium is a Dyslipidaemic agent, which act as a selective competitive inhibitor of HMG CoA educates enzyme and is used in the treatment of hyperlipidemia. Methods: In the present work, Solid Dispersion was prepared by kneading method to increase the solubility of Rosuvastatin Calcium. Results: Solid dispersions were evaluated by determining percentage yield, drug content, solubility, Scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), DSC and in vitro dissolution profile. The prepared solid dispersion are formulated into capsule dosage form and characterized by various parameters i.e. weight variation, content uniformity, disintegration and dissolution. The evaluated parameters of capsule dosage form increase in solubility and dissolution rate of the pure drug. Conclusion: These are various techniques to enhance the solubility of the drug, such as particle size reduction, use of surfactants, solid dispersion etc. Carriers are the major players in these formulations, e. g. Hydroxypropylmethylcellulose, ethylcellulose, Carbopol, Acacia Gum etc. Carbopol and Acacia Gum is one of the most efficient polymers work as a carrier for these drugs to enhance solubility.