The Fluidized Bed Coating Strategy for Developing Curcumin Solid Dispersion Pellets with Enhanced Solubility and Stability

Background and Objectives: Inflammatory Bowel Disease (IBD) is a group of inflammatory conditions of the colon and small intestine. Crohn's disease and ulcerative colitis are the principal types of inflammatory bowel disease. IBD is a complex disease which arises as a result of the interaction of environmental and genetic factors leading to immunological responses and inflammation in the intestine. Curcumin, a yellow coloring agent is used as a remedy for the treatment and prevention of inflammatory disease. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. Methods: An attempt was made to formulate sustained release pellets of curcumin using Carboxymethyl Tamarind Seed Polysaccharide (CMTSP). Solid dispersion of curcumin prepared using soluplus and incorporated into pellets for enhanced solubility and bioavailability. A central composite design was applied to study the effect of independent variables (amount of microcrystalline cellulose MCC and CMTSP) on crushing strength and drug release of pellets. In vivo study of solid dispersion loaded pellets revealed the presence of more amount of drug in plasma than pure drug loaded pellets. Result: Dissolution and absorption of curcumin were found to be increased by 1.5 and 2 fold, respectively. Conclusion: Carboxymethyl tamarind seed polysaccharide can be used successfully for colon targeted drug delivery system in the form of pellets. The percent permeability of pellets prepared by using solid dispersion was found to be more than pellets prepared by using pure drug. Curcumin has an advantageous safety profile as well as low relativecost, making it an attractive option for IBD patients. Keywords: Soluplus, carboxymethyl tamarind seed polysaccharide, extrusion-spheronization, solid dispersion pellets, inflammatory bowel disease, curcumin.

Curcumin-betaine solid dispersion for enhancing curcumin dissolution and potentiating pharmacological synergism in gastric cancer cells

Background: This study investigates the inclusion complex of curcumin (CMN) enhance the solubility, which can be utilized for the treatment of colorectal cancer (CRC) greater to free CMN. Methods: CMN solid dispersion (SD) prepared by a hot melt method using CMN with several carriers of poloxamers (P-407 and P-188), gelucire 50/13 (GLR) and mannitol (MNT). Prior, molecular modelling and phase solubility studieswere performed with drug and carriers. The SD characterized by in vitrodrug release, SEM and functionalize dyeing test. Additionally, the cytotoxicity and image of apoptosisresolved to utilize the colorectal adenocarcinoma cell lines. Results: The result showed that CMN-P-407 inclusion complex produced significant properties towards solubility (318 ± 14.46 fold) and dissolution (91 ± 0.431% at 30 min). Similarly, these data fit with insilico model. The IC50 value for inclusion complex found to be 74 and 52 µM/mL, while that for free CMN ranged from 146 and 116 µM/mL on the SW480 and Caco-2 cells respectively. Apoptosis study described that the cells are undergoing cell death by apoptosis and the small number of necrosis. Conclusion: The profound efficiency of CMN-P-407 SD indicated its potential application for CRC treatment by showing a higher capability of inhibiting cell growth compared to that of free CMN.

Delivery of curcumin in a carboxymethyl cellulose and hydroxypropyl methyl cellulose carrier: Physicochemical properties and biological activity

Ethylcellulose film coating of guaifenesin-loaded pellets: A comprehensive evaluation of the manufacturing process to prevent drug migration

Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol® HS15 as a carrier

Itraconazole (ITZ) is a class II drug according to the biopharmaceutical classification system. Its solubility is pH 3-dependent, and it is poorly water-soluble. Its pKa is 3.7, which makes it a weak base drug. The aim of this study was to prepare solid dispersion (SD) pellets to enhance the release of ITZ into the gastrointestinal environment using hot-melt extrusion (HME) technology and a pelletizer. The pellets were then filled into capsules and evaluated in vitro and in vivo. The ITZ changed from a crystalline state to an amorphous state during the HME process, as determined using DSC and PXRD. In addition, its release into the gastrointestinal tract was enhanced, as was the level of ITZ recrystallization, which was lower than the marketed drug (Sporanox®), as assessed using an in vitro method. In the in vivo study that was carried out in rats, the AUC0–48h of the commercial formulation, Sporanox®, was 1073.9 ± 314.7 ng·h·mL−1, and the bioavailability of the SD pellet (2969.7 ± 720.6 ng·h·mL−1) was three-fold higher than that of Sporanox® (*** p < 0.001). The results of the in vivo test in beagle dogs revealed that the AUC0–24h of the SD-1 pellet (which was designed to enhance drug release into gastric fluids) was 3.37 ± 3.28 μg·h·mL−1 and that of the SD-2 pellet (which was designed to enhance drug release in intestinal fluids) was 7.50 ± 4.50 μg·h·mL−1. The AUC of the SD-2 pellet was 2.2 times higher than that of the SD-1 pellet. Based on pharmacokinetic data, ITZ would exist in a supersaturated state in the area of drug absorption. These results indicated that the absorption area is critical for improving the bioavailability of ITZ. Consequently, the bioavailability of ITZ could be improved by inhibiting precipitation in the absorption area.

A Scalable Preparation Method for SILP and SCILL Ionic Liquid Thin Film Materials: Fluidized Bed Coating

The purpose of this work was to investigate the effect that changes in design and process variables had on the movement of particles around a fluidized bed coating apparatus. To measure the mean and variance of the particle cycle time distribution (CTD), the number of passages taken by a magnetic tracer particle through the spray zone was measured by a detector coil wound around the partition. The reproducibility of the measurement technique was tested by taking repeated measurements of the tracer particle movement, using similar bed operating conditions, and the method was found to give reproducible results. A series of experiments was carried out by varying operating conditions such as the partition gap, fluidizing air rate, and partition diameter and length, and measuring the change in the rate at which the tracer particle circulated in the coating device. The results of the experiments showed that, over the range of parameters tested in this work, the partition gap had the strongest influence on the rate of particle circulation. Moreover, for the 6-in.-diameter Wurster process used in the current work, the mean circulation time for the 1.1-mm-diameter Nu-Pareil particles was found to vary over the range of 2.2–10.4 sec. In addition, the mean and standard deviation of the CTD could be linearly correlated over a wide range of operating conditions, with a correlation coefficient of 0.80. Finally, an estimate of the variability in mass coating uniformity was made based on the results from the cycle time distributions. It was concluded that the effect of variability in the CTD could account for only a small fraction of the variability in the observed mass coating distribution.

Curcumin (cur) elicits a wide spectrum of potent responses for local treatment of oral disorders. However, its clinical use in the oral cavity is limited by its poor solubility and chemical instability at salivary pH. This study aims to develop cur mucoadhesive buccal tablet formulation with enhanced cur solubility and stability. For this purpose, a rapidly dissolving solid dispersion (SD) was developed using PVP (Kollidon®25). In addition, chemical stability in phosphate buffer saline (PBS) pH 6.8 was investigated for the first time using different stabilizers to ensure cur stability for in-vitro and in-vivo studies. After addressing solubility and stability challenges, buccal tablets formulations were developed using Hydroxypropyl methylcellulose (HPMC) and Carboxymethyl cellulose (CMC sodium) mixture in different ratios with or without SLS as stabilizer.Tablets containing HPMC.K15M: CMC sodium (5:1), SD (1:3), and 15 mg SLS showed the best results regarding mucoadhesive strength, in-vivo residence time, and release rate profile and were considered as the optimized formulation. The optimized formulation ensured cur stability as well as a controlled release rate, with considerable cur levels in saliva for over 12h. Preliminary clinical evaluation showed remarkable anti-inflammatory and healing effects in patients with aphthous ulcer, concluding that cur stabilized mucoadhesive formulation can efficiently treat various inflammatory oral diseases.

Objectives This study aimed to develop and optimize telmisartan (TLS)-curcumin (Cur) solid dispersion nanoparticles (SDNs) to improve the management of diabetic nephropathy (DN) by enhancing TLS’s solubility and release rate. Methods A Box–Behnken design (BBD) was used to optimize the formulation with critical excipients PVP VA S630 and Poloxamer 407. Pre-formulation studies assessed TLS’s solubility and lipophilic nature. The optimized formulation (TLS-15) was evaluated for solubility, drug release, particle size, zeta potential, and in vitro release. A comparison was made with a formulation without Cur (TLS-15 WC). TEM imaging and release kinetics analysis were conducted. Results The optimized formulation (TLS-15) demonstrated significantly improved solubility (4.801 μg/mL) and drug release (99.68%) with an appropriate particle size (303.5 nm) and zeta potential (−12.17 mV). TLS-15 WC exhibited lower values for solubility (4.74 μg/mL), drug release (98.3%), particle size (291.2 nm), and zeta potential (−25.4 mV). TEM revealed uniformly distributed spherical nanoparticles (NPs). TLS-15 showed a 99.54% release after 6 h, compared to 98.3% for TLS-15 WC, following first-order release kinetics (R 2 = 0.9934). Conclusions The study successfully developed and optimized TLS-Cur SDNs, enhancing TLS’s solubility and release. Cur played a critical role in boosting the therapeutic potential of the formulation. While challenges remain with stability and manufacturing, the formulation shows promise for improving bioavailability and efficacy in DN treatment. However, additional studies are needed to validate its effectiveness.

Chapter Perspectives of Fluidized Bed Coating in the Food Industry

The study concerns the coating process of metal substrates in an electrostatic fluidized bed (EFB). This eco-friendly process is profitably used to coat components of particularly complex shapes. Although this technology is widely spread in several industrial domains, the implementation of appropriate process control procedures is still object of investigation. A model was generated from experimental data with the aim of predicting, for any set of process parameters, the resulting coating thickness of the sample. With a design of experiment (DOE) approach, the experimental investigation, that is the base for the model, quantifies the coating thickness as a function of the main process parameters namely coating time, applied voltage, and gas flow rate fed into the fluidized bed. This study addresses the effect of the inherent uncertainties on the predicted coating thickness caused by the approximation in the model parameters. In particular, a fuzzy-logic based approach is used to describe the model uncertainties and the transformation method is used to propagate their effect on the thickness. The fuzzy results are then compared with the data produced by the experimentation leading to the evaluation of the membership level of the dataset to the uncertain model.