Enhancement Of Aqueous Solubility Research Articles

Modification of physicochemical properties of chitosan to improve its pharmaceutical and agrochemical potential applications

Chitosan has received much more attention as a functional biopolymer with applications in pharmaceuticals, agricultural, drug delivery systems and cosmetics.The objectives of present investigation were to carry out modification of chitosan for enhancement of aqueous solubility, which will impart increased solubility and dissolution rate of poorly soluble drug itraconazole (ITZ) and also evaluate the modified chitosan for soyabean seed germination studies.The modification of chitosan was accomplished through the antisolvent precipitation method; employing five carboxylic acids. The resulting products were assessed for changes in molecular weight, degree of deacetylation, solubility and solid state characterization. Subsequently, the modified chitosan was complexed with itraconazole using the co-grinding technique. The prepared formulations were evaluated for solubility, FTIR (Fourier-transform infrared spectroscopy), PXRD (Powder X-ray diffraction), in-vitro dissolution studies. Furthermore the effect of modified chitosan has been evaluated on soybean seed germination.Results demonstrated that, modified chitosan improves self and solubility of itraconazole by six folds. As there was increased degree of deacetylation of chitosan leads to improvement in solubility. The results of FTIR showed the slight shifting of peaks in co-grind formulations of itraconazole. Formulations showed reduction in crystallinity of drug which leads to enhancement in dissolution rate as compared to pure itraconazole. Retention of property of seed germination was observed with modified chitosan at optimum concentration of 3 % w/v, with benefit of enhanced aqueous solubility of chitosan.This positive result paves the way for the advancement of pharmaceutical and agrochemical products employing derivatives of chitosan.

Inclusion and Non‐Inclusion Complexes between Curcumin and β‐Cyclodextrin with High‐Curcumin Loading and Enhanced Aqueous Solubility Obtained by Mechanochemistry

AbstractIn this study, we employ mechanochemistry as an innovative strategy, using a Planetary Mill, to obtain supramolecular structures in the solid state between Curcumin (Cur) and β‐cyclodextrin (βCD), exploring different parameters such as jars and balls material (stainless steel versus zirconium oxide), milling time, as well as the effect on imposing different Cur:βCD molar ratios. Our findings demonstrate that regardless of the milling material used, the same supramolecular interactions between Cur and βCD seem to be promoted. However, depending on the molar ratio, different supramolecular modes are produced resulting in inclusion complexes (ICs) or non‐inclusion complexes (non‐ICs) by a partial or total amorphization of both Cur and βCD. Independently of the type of supramolecular complex obtained (ICs/or non‐ICs), high content of Cur was quantified in all the systems, achieving a Cur content of up to 342 mg per mmol of βCD, along with an enhancement in Cur aqueous solubility. The Cur:βCD 1 : 2 complex showed the highest aqueous solubility (around 10‐times more soluble than milled Cur). In our conditions, the optimum time to form the supramolecular complexes was 60 min. The stability of the complexes was directly related to the extent of encapsulation of Cur inside the βCD cavity.

Characterisation of the apparent aqueous solubility enhancement of testosterone analogues in micelles of dodecyl-chained surfactants with different headgroups

The solubilisation capacities of the micelles formed by a range of surfactants possessing a dodecyl (C12) hydrocarbon ‘tail’ and a variety of hydrophilic ‘headgroups’ have been studied for a range of hydrophobic steroids (testosterone (T) and its propionate (TP) and enanthate (TE) esters). The solubilisation studies were performed at ambient temperature, with drug concentration monitored (over 48–72 h) by UV absorbance. The various surfactant systems were characterised in terms of their physicochemical properties, including their surface tension, critical micelle concentration, viscosity, and density. Results show that while the apparent aqueous solubility of the poorly water-soluble steroids increases upon solubilisation within the surfactant micelles, the extent of this increase varies with the nature of the hydrophilic headgroup and the hydrophobicity of the drug. Specifically, changing the surfactant headgroup from non-ionic to zwitterionic, then to ionic, results in a marked increase in solubility of the two least hydrophobic steroids, testosterone and testosterone propionate, suggesting rather counter-intuitively that these steroidal drugs tend to associate to a greater extent with micelles formed by surfactants with more hydrophilic/charged head groups. The more hydrophobic steroid, TE, was solubilised to the greatest extent, being predominantly solubilised within the micelle core. In this case, the influence of surfactant head group on TE solubilisation was less obvious, with surfactants containing ionic and zwitterionic head groups exhibiting high levels of solubilisation. The physicochemical properties that had most influence on solubilisation of the testosterone analogues, as evaluated using multiple linear regression, were micelle shape for T and TP, and critical micelle concentration for TE. Through the findings of this comparative study, the essential molecular descriptors of optimal solubilisation for improved drug delivery and the loci of solubilisation of the testosterone analogues have been identified.

Solid-form screening and absolute structure determination of antithrombotic diastereomers S007–867 and S007–1175

Two novel anti-thrombotic diastereomers S007–867 and S007–1175 had been recently identified by CSIR-CDRI. We performed extensive experimental solid-form screening studies on the most active diastereomer S007–867, which led to the identification of several new solid-forms (two polymorphs, a benzene solvate, and two plausible multi-component forms). Whereas, a single crystal form is identified for the less active diastereomer S007–1175. All newly identified crystalline forms of the two diastereomers were thoroughly characterized with the help of differential scanning calorimetry and X-ray diffraction. We also evaluated the contributions made by various atom···atom contacts in their crystal structures with the help of Hirshfeld surface analysis. Physicochemical property evaluation of the solid-forms of S007–867 reveals ∼2-fold enhancement in aqueous solubility for the 1:2 succinic acid eutectic mixture. We also report the full absolute structure determination of both diastereomers along with the chiral precursor, tert‑butyl N-(3(S)-piperidyl methyl)carbamate used in the synthesis of S007–867 from the single-crystal X-ray diffraction.

Hot Melt Extruded Posaconazole-Based Amorphous Solid Dispersions-The Effect of Different Types of Polymers.

Four model polymers, representing (i) amorphous homopolymers (Kollidon K30, K30), (ii) amorphous heteropolymers (Kollidon VA64, KVA), (iii) semi-crystalline homopolymers (Parteck MXP, PXP), and (iv) semi-crystalline heteropolymers (Kollicoat IR, KIR), were examined for their effectiveness in creating posaconazole-based amorphous solid dispersions (ASDs). Posaconazole (POS) is a triazole antifungal drug that has activity against Candida and Aspergillus species, belonging to class II of the biopharmaceutics classification system (BCS). This means that this active pharmaceutical ingredient (API) is characterized by solubility-limited bioavailability. Thus, one of the aims of its formulation as an ASD was to improve its aqueous solubility. Investigations were performed into how polymers affected the following characteristics: melting point depression of the API, miscibility and homogeneity with POS, improvement of the amorphous API's physical stability, melt viscosity (and associated with it, drug loading), extrudability, API content in the extrudate, long term physical stability of the amorphous POS in the binary drug-polymer system (in the form of the extrudate), solubility, and dissolution rate of hot melt extrusion (HME) systems. The obtained results led us to conclude that the physical stability of the POS-based system increases with the increasing amorphousness of the employed excipient. Copolymers, compared to homopolymers, display greater homogeneity of the investigated composition. However, the enhancement in aqueous solubility was significantly higher after utilizing the homopolymeric, compared to the copolymeric, excipients. Considering all of the investigated parameters, the most effective additive in the formation of a POS-based ASD is an amorphous homopolymer-K30.

Production challenges of tablets containing lipid excipients: Case study using cannabidiol as drug model

The aims of this study were, firstly, to select an optimal lipid solid dispersion of cannabidiol among different lipid excipients (Gelucire® 50/13, 48/16, 44/14 and Labrasol®) and inorganic carriers (colloidal silica, Syloid® XDP and Neusilin® US2) through a screening plan. The enhancement of aqueous solubility of cannabidiol from a free-flowing powder with adequate drug content was obtained by mixing cannabidiol (20%) with Gelucire® 50/13 (40%; Gattefossé, France), both incorporated inside mesopores of mesoporous silica Syloid® XDP (40%; Grace, Germany). Secondly, we have studied the tableting properties of this selected dispersion through a Design of Experiments (DoE) by manufacturing tablets with other excipients with using a compression simulator (Styl’One® Evo, Medelpharm, France). The design of experiments included the percentage of lipid solid dispersion, of glidant, of lubricant and different compression forces. The dissolution efficiency, the drug content, the tensile strength and the ejection force were analyzed. The DoE showed that % of dispersion as well as compression forces were the main influential variables. An exit of lipid materials outside the mesopores of silica due to compression process has been highlighted, reflected by reduced tensile strength. This study showed the possibility of manufacturing tablets with lipid materials even if limitations have been highlighted. Indeed, the dispersion percentage must not exceed 27% and compression forces up to 13 kN are required to produce lipid tablets with optimal properties.

Paliperidone-benzamide Cocrystals: Preparation, Characterization, In Vitro/In Vivo Evaluation

Background: The current investigation contributes to the development of novel Paliperidone (PPD) co-crystals (CCs) using benzamide (BZ) as a conformer. The CCs were synthesized using the solvent evaporation technique. Methods: The enhancement in solubility was studied by saturation solubility studies. Structural characterization of CCs was performed by Fourier Transform Infra-Red Spectroscopy (FTIR), powder X-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM) and Proton Nuclear Magnetic Resonance (1H- FT NMR) to verify CC formation. Results: CCs exhibited a higher aqueous solubility of 2.067±0.004mg/ml when compared to pure drug 0.473±0.012mg/ml. This designated aqueous solubility enhancement of CCs by 4.36 folds. In vitro dissolution data of the CCs exhibited a drug release of 96.5±1.63% in 60min, while pure drug showed a poor release of 37.8±1.76% in the same time period In vivo studies resulted in enhanced rate and extent of drug absorption from CCs when compared to drug suspension. Conclusion: CCs formed between PPD and BZ present a novel approach in overcoming the hurdles in the solubility of PPD that exhibits poor aqueous solubility.

Review: Hydrotropy as Prominent Approach for Enhancement of Aqueous Solubility of Drugs

Solubility is crucial element to achieve the desired drug absorption in the total pharmacological response. Low water solubility can considerably limit the medication efficacy, and to improve aqueous solubility, a variety of approaches are employed. The capacity which increases water solubility for particular drug can thus be a useful tool for enhancing efficiency and/or decreasing negative effects. This is true for parental administered, topically applied and orally consumed solutions. It is a difficult work for researchers and pharmaceutical scientist to use solubility features in bioavailability, pharmacological effect and solubility enhancement of diverse weakly soluble substance. Hydrotropy is one of the strategies for increasing solubility. The purpose of this paper is to examine the hydrotropy Solubilization technique and to highlight the mechanism and different prospective of this method.
 Keywords: Hydrotropy, mechanism, formation of hydrotropes, Solubility

Enhancement in aqueous solubility of sulindac medicine by using the micellar solution of ionic and non-ionic surfactants

In the science of pharmacology, solubility plays a crucial role in the efficacy and bioavailability of the drug. Utilizing solubility features to improve the bioavailability and pharmacological effect of diverse weakly soluble substances, is an arduous task for pharmaceutical experts and researchers. Particle size, surface area, physicochemical qualities, physical forms of drugs, solvents and surfactant usage are parameters that influence solubility. The objective of the current study was to enhance the solubility of the non-steroidal anti-inflammatory drug (NSAID): Sulindac. The micellar solutions method was employed with different surfactants to increase the efficiency. Both nonionic (Tween 20, 40, 60 and 80 with Brij 30, 35 and 56) and ionic (SDS, SDBS, CTAB, TTAB and DTAB) surfactants were investigated for their effect on drug solubility in aqueous solution. Various parameters of surfactant solutions such as aggregation number, micelle-water partition coefficient (KM), molar solubilization ratio (MSR), Gibbs energy of solubilization (∆Gº s), size of micelle and binding constant of the drug micelles were measured. Finding reveals that the use of mentioned surfactant is an excellent approach to enhancing the solubility of sulindac. Furthermore, the present work provides an understanding of the relation of aqueous solubility with aggregation number and structure of surfactants used.

Solubility enhancement of some poorly soluble drugs by solid dispersion using Ziziphus spina-christi gum polymer

A high percentage of marketed drugs suffer from poor water solubility and require an appropriate technique to increase their solubility. This study aims to compare physically modified and unmodified gum polymers extracted from Ziziphus spina-christi fruits as solid dispersion carriers for some drugs. Taguchi Orthogonal Design (L9) was chosen for the screening and optimization of the solid dispersions. The design has four factors: type of drug, type of polymer, type of solid dispersion process, and drug to polymer ratio. Each factor was varied in three stages and the total number of runs was 9 in triplicate. The polymer was physically modified by heating (M1ZG) or freeze-drying (M2ZG). The drugs were selected according to the biopharmaceutical classification system, namely loratadine and glimepiride (class II) and furosemide (class IV). Drugs were dispersed in the polymer in three different ratios 1: 1, 1: 2, and 1: 3. Solid dispersions were made by co-grinding, solvent evaporation, and kneading methods. Modified and unmodified polymers were characterized in terms of their organoleptic properties, solubility, powder flowability, density, viscosity, swelling index, and water retention capacity. Solid dispersions were characterized in terms of percentage practical yield, solubility improvement, and drug compatibility. The results showed that the organoleptic properties of polymers were not changed by the gum modification. The swelling index of the polymer was doubled in M1ZG. The viscosity and water retention capacity of the polymer was increased in both modified polymers. All solid dispersions showed a high practical percentage yield of more than 93%, the higher values ​​being more associated with loratadine and furosemide than with glimepiride. The improvement in solubility was observed in all solid dispersions prepared, the values ​​varying with the pH of the medium and the method of modification. The FTIR results indicated that there was no chemical interaction between these drugs and the polymer used. Analysis of the results according to the Taguchi orthogonal design indicated 51 folds aqueous solubility enhancement for loratadine using M2ZG polymer at a ratio of 1: 3 of Drug: polymer. This study showed the possibility of improving the solubility of other poorly soluble drugs.

Enhancement of Aqueous Solubility, Dissolution Profile, and Oral Bioavailability of Pentoxifylline by Microsponges

Microsponge, a novel drug delivery system, is designed to deliver a pharmaceutically active ingredient efficiently at the minimum dose. Microsponge plays an important role in enhancing drug stability, reducing side effects, and modifying drug release profiles. It is mostly used for transdermal delivery. Recent studies also explored their use for oral administration. This study aimed to explore the potential use of the microsponge technique in improving the aqueous solubility and dissolution profile of pentoxifylline (PTX). In this study, microsponges were prepared by a quasi-emulsion solvent diffusion method by varying concentrations of carriers. Nine different ratios of the PTX:Eudragit E-100 with varying amounts of dichloromethane were used. All formulated microsponges were evaluated for %production yield, compatibility of drug excipient, encapsulation efficiency, in vitro drug release, and in vivo bioavailability, as well as recorded by scanning electron microscopy (SEM) and differential scanning calorimetry(DSC). Our data suggested that the aqueous solubility of PTX microsponges was four times greater than that of pure drug. The in vitro drug release of selected microsponges (M8) was found to be 70%; furthermore, the in vivo study suggested that the selected formulation significantly enhanced drug concentration in the plasma (9,219 ng/mL in 12 hours) in comparison to pure drug PTX (2,476 ng/mL in 12 hours). SEM showed that the prepared microsponges were spherical with porous nature. Fourier-transform infrared spectroscopy and DSC studies confirmed an absence of incompatibility among drugs and selected excipients. The pH of the selected gel was found to be 6.8, which was compatible with those of skin and oral formulations also. All above data suggested a highly successful and beneficial use of the microsponge technique in enhancing aqueous solubility, dissolution profile, and oral bioavailability of PTX. Microsponge-based delivery of PTX may represent an alternative strategy to improve the bioavailability of the drug.

Synthesis of Purine-Based Ionic Liquids and Their Applications.

Bio-based ionic liquids (ILs) are being increasingly sought after, as they are more sustainable and eco-friendly. Purines are the most widely distributed, naturally occurring N-heterocycles, but their low water-solubility limits their application. In this work, four purines (theobromine, theophylline, xanthine, and uric acid) were combined with the cation tetrabutylammonium to synthesize bio-based ILs. The physico–chemical properties of the purine-based ILs were characterized, including their melting and decomposition temperatures and water-solubility. The ecotoxicity against the microalgae Raphidocelis subcapitata was also determined. The ILs show good thermal stability (>457 K) and an aqueous solubility enhancement ranging from 53- to 870-fold, in comparison to their respective purine percursors, unlocking new prospects for their application where aqueous solutions are demanded. The ecotoxicity of these ILs seems to be dominated by the cation, and it is similar to chloride-based IL, emphasizing that the use of natural anions does not necessarily translate to more benign ILs. The application of the novel ILs in the formation of aqueous biphasic systems (ABS), and as solubility enhancers, was also evaluated. The ILs were able to form ABS with sodium sulfate and tripotassium citrate salts. The development of thermoresponsive ABS, using sodium sulfate as a salting-out agent, was accomplished, with the ILs having different thermosensitivities. In addition, the purine-based ILs acted as solubility enhancers of ferulic acid in aqueous solution.

Colloidal and vesicular delivery system for herbal bioactive constituents.

The main objective of the present review is to explore and examine the effectiveness of currently developed novel techniques to resolve the issues which are associated with the herbal constituents/extract. A systematic thorough search and collection of reviewed information from Science direct, PubMed and Google Scholar databases based on various sets of key phrases have been performed. All the findings from these data have been studied and briefed based on their relevant and irrelevant information. Herbal drugs are gaining more popularity in the modern world due to their applications in curing various ailments with minimum toxic effects, side effect or adverse effect. However, various challenges exist with herbal extracts/plant actives such as poor solubility (water/lipid), poor permeation, lack of targeting specificity, instability in highly acidic pH, and liver metabolism, etc. Nowadays with the expansion in the technology, novel drug delivery system provides avenues and newer opportunity towards the delivery of herbal drugs with improved physical chemical properties, pharmacokinetic and pharmacodynamic. Developing nano-strategies like Polymeric nanoparticles, Liposomes, Niosomes, Microspheres, Phytosomes, Nanoemulsion and Self Nano Emulsifying Drug Delivery System, etc. imparts benefits for delivery of phyto formulation and herbal bioactives. Nano formulation of phytoconstituents/ herbal extract could lead to enhancement of aqueous solubility, dissolution, bioavailability, stability, reduce toxicity, permeation, sustained delivery, protection from enzymatic degradation, etc. CONCLUSION: Based on the above findings, the conclusion can be drawn that the nano sized novel drug delivery systems of herbal and herbal bioactives have a potential future for upgrading the pharmacological action and defeating or overcoming the issues related with these constituents. The aims of the present review was to summarize and critically analyze the recent development of nano sized strategies for promising phytochemicals delivery systems along with their therapeutic applications supported by experimental evidence and discussing the opportunities for further aspects.

Development of lapatinib nanosponges for enhancing bioavailability

The present study is aimed to formulate lapatinib nanosponges (LPT NSs) to enhance its aqueous solubility and bioavailability. LPT loaded NSs were fabricated using Eudragit RS100 as polymer and polyvinyl alcohol as a stabilizer. The optimized formulation was evaluated for morphological characterization, solid-state characterization, accelerated stability studies, in vitro release studies and in vivo pharmacokinetic studies. Solid-state characterization such as Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) studies showed the retention of drug characteristics peaks in the formulation which indicates no or negligible chemical interactions between the LPT and excipients used for the formulation preparation. Morphological characterization such as Atomic Force Microscopy (AFM) and Field Emission Scanning Electron Microscopy (FESEM) confirmed the formation of nanosponges with porous structures. Saturation solubility studies and in vitro dissolution studies proved the enhancement of aqueous solubility as well as dissolution rate of LPT in the form of NSs as compared to pure form of LPT in the basic medium as compared to the acidic medium. Also, in vivo pharmacokinetic study proved significant improvement in AUC and Cmax of the LPT NSs when compared to the pure LPT. Thus LPT-loaded NSs are proven to have high bioavailability and potential scope to reduce the oral dose of LPT by preparing the NSs.

Solid Form Selection and Process Development of KO-947 Drug Substances

KO-947 is a potent, selective extracellular signal-regulated kinases (ERK) inhibitor that was investigated in the clinic for the treatment of various solid tumors. KO-947 free base, form E, was originally recommended out of 10 identified crystalline forms for the development of an oral solid dosage product. Change of clinical need shifted the focus to aqueous solubility enhancement through salt formation. Mesylate salt demonstrated remarkably increased aqueous solubility and also profound polymorphism. Anhydrous form III was initially recommended but later dropped, primarily due to the manufacturing difficulties. In the end, form IX was discovered through close collaboration between preformulation and process scientists. An elaborate manufacturing process was then devised to successfully produce mesylate salt, form IX in kilogram scale supplied for the clinical use.

Evaluation of the bioaccessibility of tetrahydrocurcumin-hyaluronic acid conjugate using in vitro and ex vivo models

Tetrahydrocurcumin-hyaluronic acid (THC-HA) conjugate was synthesized in order to improve the bioaccessibility of tetrahydrocurcumin (THC). The successful conjugation was confirmed by the results from 1H-nuclear magnetic resonance (1H NMR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Bioaccessibility enhancement from the THC-HA conjugate compared to the free crystalline THC suspension was demonstrated by the results from ex vivo Franz diffusion cell using small intestine from porcine and in vitro TNO dynamic gastrointestinal model-1 (TIM-1). Additionally, in vitro release was studied, and the integrity of the conjugate in both simulated gastric and intestinal conditions was found to maintain for up to 4 h. Mucoadhesive assay and rheological results indicated that the mucoadhesive property of THC-HA, in combination with the aqueous solubility enhancement, might contribute to the increased bioaccessibility. This study provides a promising approach to enhance the bioaccessibility of tetrahydrocurcumin through the innovative conjugation with hyaluronic acid.

Environment safe Method development and Validation of Dolutegravir in Bulk and Tablet dosage form by UV-Visible spectroscopy

To develop an environment-safe aqueous solubility enhancement method of poorly water-soluble drugs is the need of the pharmaceutical field. Because when organic solvents were used for solubility enhancement, there are many disadvantages like carcinogenicity, environment pollutant, flammable, toxicity, and cost. The hydrotropic method has been used to enhance the aqueous solubility of poorly water-soluble drugs. Dolutegravir is slightly soluble in water. To enhance aqueous solubility various hydrotropes were used and optimized the concentration of each hydrotrope. From these hydrotropes, a mixture of 10% sodium tricitrate and 10% sodium benzoate was selected because Dolutegravir was completely soluble in a mixed hydrotropic solution. Method development and analytical validation were performed. The maximum wavelength of Dolutegravir in the hydrotropic mixture was found a 268nm, and the linearity curve in the range of 5-25µg/ml. A regression coefficient was found to be 0.999. Percent label claim, accuracy (% RSD) were found 99.58%, 0.13(80%), 0.11(100%), 0.13(120%), respectively. The LOD for Dolutegravir was determined to be 0.037μg/ mL, and LOQ was found to be 0.11μg/mL.

Formulation and characterization of ternary amorphous solid dispersions of a highly potent anti-tubercular agent and curcumin

The enhancement of aqueous solubility of poorly water-soluble drugs is a challenge. Additional hurdle is to enhance the solubility of more than one drugs in same formulation for the combination therapy. This research paper presents the development of novel amorphous ternary (drug-drug-hydrophilic polymer) solid dispersions to simultaneously enhance the aqueous solubility and stability of two poorly soluble drugs. The ternary amorphous solid dispersions in the study contains the combination of a highly potent and novel anti-tubercular agent, Indole2-carboxamide derivative (North 2) and anti-oxidant, curcumin (CUR). Binary and ternary amorphous dispersions of North 2 and CUR were prepared using hydrophilic polymers, namely polyvinylpyrrolidone (PVP), Eudragit EPO® (EPO), and hydroxypropyl methylcellulose (HPMC), at 1:1 w/w (for binary solid dispersions) and at 1:1:2 w/w/w (for ternary solid dispersions) ratios. Differential scanning calorimetry (DSC) studies showed that North 2 has high crystallization tendency and formed an amorphous binary solid dispersion with only EPO, whereas CUR was characterized as low crystallization tendency compound and formed amorphous binary solid dispersions with EPO, PVP, and HPMC. All the three polymers formed amorphous ternary solid dispersions at 1:1:2 w/w/w ratios. Fourier transform infrared spectroscopy (FTIR) data showed significant peak shifts in both binary and ternary dispersions of North 2/CUR indicating molecular interactions. These interactions mainly involved the carbonyl group of both compounds, indole –NH of North 2 and phenolic –OH of CUR with the polymer chain. These interactions were confirmed by solution NMR and molecular modeling studies. In dissolution studies, out of the three hydrophilic polymers, EPO showed maximum solubility enhancement with and increased solubility by 55 and 59 times for North 2 and CUR, respectively, within 12 h. XRD stability data of the ternary solid dispersions showed that they were stable over 90 days at room temperature. The aqueous solubility of North 2 and curcumin was enhanced successfully with 50% loading of the drugs. Hence, this study shows the potential of designing ternary dispersions to achieve the solubility enhancement of a combination of poorly soluble drugs by utilizing a molecularly interacting hydrophilic polymer.

Efficient Amyloid Fibrillation Inhibition and Remodeling of Preformed Fibrils of Bovine Insulin by Propolis Polyphenols-Based Nanosheets.

Among common strategies for amyloid fibrillation inhibition, the use of naturally occurring polyphenols as an efficient therapeutic approach has attracted a growing body of attention. However, the poor water solubility and low bioavailability of these compounds have greatly restricted their clinical application in amyloid-related diseases. Thus, different types of formulations have been developed to overcome these limitations; among them, nanonization appears to be one of the most notable approaches. Herein, we show that the polyphenolic fraction of propolis (PFP), in the nanosheet form (PFP nanosheet), exhibits an improved capacity for amyloid fibrillation inhibition as well as clearance of preformed fibrils of bovine insulin. This increased efficiency is suggested to be related to the aqueous solubility and surface area enhancement as well as surface modifications upon undergoing the nanonization process, which can lead to strong binding with and trapping of protein at the surface of the nanosheets. On the basis of thioflavin T results, it is suggested that although PFP may modulate the fibrillation process via shortening of the lag phase, prolongation of the nucleation phase through interaction with and stabilizing monomeric species is the mechanism of action of PFP nanosheets. We propose that nanonization of natural small molecules can be considered as a powerful approach to improve their anti-amyloidogenic properties and overcome obstacles originating from poor water solubility and low bioavailability of drug candidates relating to neurodegenerative diseases. Taken together, the obtained results may suggest PFP nanosheets as a potential candidate for use against neurological disorders.

FORMULATION AND EVALUATION OF SOLID DISPERSION TABLETS OF FUROSEMIDE USING POLYVINYLPYRROLIDONE K-30

Objective: The objective of the present study was to improve the aqueous solubility and dissolution characteristics of the loop diuretic furosemide (FUR); a class IV drug in the Biopharmaceutical Classification System (BCS) using solid dispersion technique.
 Methods: Solvent evaporation and kneading methods were used to produce solid dispersions of FUR in different ratios with the hydrophilic carrier polyvinylpyrrolidone K-30 (PVP-K30). The prepared solid dispersions were evaluated in terms of solubility study, percentage yield, drug content and Fourier transform infrared spectroscopic study (FT-IR). Tablets containing the optimized formula of solid dispersions ( were formulated and their dissolution characteristics were compared with commercial furosemide tablets.
 Results: The prepared solid dispersions showed an increase in aqueous solubility, especially those formulated in a 1:2 drug: carrier ratio using solvent evaporation method ( it showed a four-fold increase in solubility compared to the parent drug. The absence of drug-carrier chemical interactions that could affect the dissolution was proved by FT-IR. Solid dispersion tablets exhibited a better dissolution profile in simulated gastric fluid pH 1.2 at 37°C ± 0.5 than the commercial FUR tablets in terms of mean dissolution time (8.44 min) and dissolution efficiency in 30 min (42.54%). Both FUR solid dispersions and commercial tablets followed Weibull and Krosmeyer models as the two best models of drug release kinetics proving that they were immediate release.
 Conclusion: According to the results obtained in this study, solid dispersion techniques could be successfully used for the enhancement of aqueous solubility and dissolution rate of FUR.