Solubility Enhancement Research Articles

Preparation, Characterization and In-vitro Evaluation of Nano Encapsulated 1-Octacosanol for Solubility Enhancing by using Various Polymers through Spray Drying Approach

This research aimed to develop a nano-encapsulated free-flow powder of 1-octacosanol for functional food application. We had prepared stable green nano-emulsion oil in water by Dyno Mill and spray dryer for free flow powder by using different polymers (Hydroxypropyl methylcellulose, polyvinylpyrrolidone, octenyl succinate starches) as hydrophilic polymers in different ratios for enhancing the solubility. Zeta potential, X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR), encapsulation efficiency, particle size distribution, surface morphology, differential scanning calorimetry spectroscopy and in-vitro dissolution research were used to analyze 1-octacosanol. The optimized nano-emulsion preparation F15 consists of an average particle size 720.9 nm, zeta potential -24.5 mV shows stable nano-emulsion oil in water type, and encapsulation efficiency was found to be 96.76%, FTIR studies did not show any evidence of interaction between the herbal extract and the polymers. XRD shows the conversion of crystalline to amorphous nature of powder. In differential scanning calorimetry (DSC), spectroscopy studies found three major peaks in standard herbal extract peaks is 60.21, 67.16, 81.27°C and nano-encapsulated spray dried powder peaks are 58.18, 66.44, 79.25°C with minor moisture absorbed by the polymer in formulation. This evaluation shows significant improvement between normal herbal extract of 1-octacosanol and encapsulated spray-dried powder of 1-octacosanol for functional food application successfully improving the water solubility without changing a structural and chemical properties of the 1-octacosanol crystal.

Buccal delivery system of active pharmaceutical ingredients-ionic liquid (API-IL): Effects of API-IL loading and gelatin film concentration

Ionic liquid (IL) salt of active pharmaceutical ingredient (API) represents a promising formulation strategy to address low drug solubility and polymorphism prevalent in API solid crystals. The present work developed for the first time a buccal delivery system of API-IL via fast-dissolving API-IL-loaded gelatin films. Imidazolium-based ibuprofen salt was used as the model API-IL. The effects of API-IL loading and gelatin concentration on the film’s (i) mechanical strength, (ii) inter-batch uniformity in the films’ API payload, weight, and thickness, (iii) thermal stability, (iv) API dissolution and solubility enhancement were investigated. The plasticizer role of API-IL was evident, where minimum 30 wt% API-IL loading was needed to produce flexible yet mechanically-strong films. Lower API-IL loading produced brittle films due to insufficient plasticization facilitated by hydrogen bond interactions between API-IL and gelatin. Gelatin concentration influenced films’ mechanical strength, weight/thickness, and API dissolution rate. Depending on the API-IL loading and gelatin concentration, films with API payload (7–30 mg/cm2), thickness (300–900 µm), and weight (20–110 mg/cm2) were produced at nearly 100% efficiency and high inter-batch uniformity. API-IL existed as amorphous liquid in the film exhibiting fast API dissolution (100% in 15 min) and high kinetic solubility (8 times thermodynamic solubility) in simulated saliva fluid.

Nanocrystals loaded collagen/alginate-based injectable hydrogels: A promising biomaterial for bioavailability improvement of hydrophobic drugs

The study aims to improve the solubility of poorly soluble drug by developing an optimized formulation of nanocrystals and extend its release profile by incorporating optimized nanocrystals in a biopolymer based injectable hydrogel. Nanocrystals of Silymarin (SM) were developed by anti-solvent precipitation technique followed by homogenization. Various stabilizers were investigated and combination of polyvinyl pyrrolidine K30 (PVP K30) and sodium lauryl sulfate (SLS) in a specific ratio was chosen as a stabilizer for nanocrystals. The optimized nanocrystals possessed mean particle size 172 ± 5.23 nm and PDI of 0.228 ± 0.02. Sodium alginate (Alg) and collagen (Col) based injectable hydrogel in combination with pluronic F127 showed good biocompatibility, mechanical strength and biodegradability. The developed formulation was characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transform infra-red spectroscopy (FT-IR) and X-ray diffraction (XRD) analysis. The results of FT-IR and TGA showed structural cross-linking between polymers and promising thermal stability of formulation with increasing temperature, respectively. The nanocrystals loaded Alg-Col-F127 injectable hydrogel was degraded completely in 48 h. The results of in vitro release studies and in vivo pharmacokinetic profiling of silymarin nanocrystals laden Alg-Col-F127 injectable hydrogel exhibited controlled release behavior as compared to coarse silymarin suspension and silymarin nanocrystals. Therefore, nanosuspension integrated biopolymer-based hybrid injectable hydrogel system may be used to assist solubility and bioavailability enhancement as well as serve as platform to provide controlled drug release.

Benzethonium chloride affects short chain fatty acids produced from anaerobic fermentation of waste activated sludge: Performance, biodegradation and mechanisms

Benzethonium chloride (BZC) is viewed as a promising disinfectant and widely applied in daily life. While studies related to its effect on waste activated sludge (WAS) anaerobic fermentation (AF) were seldom mentioned before. To understand how BZC affects AF of WAS, production of short chain fatty acids (SCFAs), characteristics of WAS as well as microbial community were evaluated during AF. Results manifested a dose-specific relationship of dosages between BZC and SCFAs and the optimum yield arrived at 2441.01 mg COD/L with the addition of 0.030 g/g TSS BZC. Spectral results and protein secondary structure variation indicated that BZC denatured proteins in the solid phase into smaller proteins or amino acids with unstable structures. It was also found that BZC could stimulate the extracellular polymeric substances secretion and reduce the surface tension of WAS, leading to the enhancement of solubilization. Beside, BZC promoted the hydrolysis stage (increased by 7.09 % to 0.030 g/g TSS BZC), but inhibited acetogenesis and methanogenesis stages (decreased by 6.85 % and 14.75 % to 0.030 g/g TSS BZC). The microbial community was also regulated by BZC to facilitate the enrichment of hydrolytic and acidizing microorganisms (i.e. Firmicutes). All these variations caused by BZC were conducive to the accumulation of SCFAs. The findings contributed to investigating the effect of BZC on AF of WAS and provided a new idea for the future study of AF mechanism.

Formulation development and characterization of luliconazole loaded−mesoporous silica nanoparticles (MCM−48) as topical hydrogel for the treatment of cutaneous candidiasis

The conventional formulation of luliconazole (LCZ) faces challenges such as poor solubility and limited skin retention upon application. Therefore, the focus of this research was to develop and characterize mesoporous silica nanoparticles (MSN) that can effectively deliver luliconazole for the treatment of cutaneous candidiasis fungal infection.The MSNs were optimized by central composite design and synthesized using the sol−gel method. Factors such as stirring time and surfactant ratio were varied to investigate their impact on particle size and Polydispersity index (PDI). Subsequently, the MSN surface was functionalized with both amine (positively charged) and phosphonate groups (negatively charged) using 3-aminopropyltriethoxysilane (APTES) and 3trihydroxysilyl propyl methylphosphonate (THMP).The efficacy of the optimized luliconazole−loaded MSNs was evaluated through various comparative studies, including in-vitro and in-vivo antifungal assessments, ex-vivo permeation and skin retention experiments, acute dermal irritation tests, and histopathological analysis. These evaluations were compared with the pure drug and a commercially available formulation.The optimized MSNs exhibited high porosity and spherical particle sizes ranging from 300 to 400 nm. They demonstrated excellent physical and chemical stability, indicating compatibility between the drug and the MSN structure. The successful loading of luliconazole into the nanopores of the MSNs was confirmed through Brunauer Emmett Teller (BET) analysis.The luliconazole−loaded MSN (LCZ−MSN) gel exhibited a controlled release profile, sustaining drug release for up to 24 h. The solubility of the drug was 12 times higher compared to the free form, and the MSNs enhanced skin retention by six−fold compared to the pure drug. In an in-vivo cutaneous candidiasis rat model, the enhanced efficacy of the MSNs was evident, highlighting the potential of this innovative approach for controlled release and solubility enhancement of poorly soluble drugs, with no observed skin irritation.Overall, this research showcases the potential of mesoporous silica nanoparticles as a promising approach for controlled delivery and improved solubility of poorly soluble drugs like luliconazole, thereby addressing the challenges associated with conventional formulations and offering a novel strategy for treating cutaneous candidiasis fungal infection.

3D printed capsule shells for personalized dosing of cyclosporine-loaded SNEDDS

Cyclosporine (CsA) is a potent immunosuppressant agent that has been used since 1980 for the treatment of various autoimmune diseases and is extensively used to enhance the survival rate of patients and grafts following organ transplant surgeries. CsA is a poorly soluble drug with a narrow therapeutic window and inter-subject variability, which can lead to graft rejection, nephrotoxicity and other severe adverse effects. This study explores a novel method that combines solubility enhancement of CsA using SNEDDS formulation and personalized dosage delivery using 3D printing technology. The oil phase was chosen as a combination of caproyl 90 and octanoic acid while the Smix phase was chosen as a combination of cremophore El and PEG 400. The optimized liquid SNEDDS was solidified using PEG 6000. An FDM printer was used to print a capsular shell with an oval base that ascends to form a dome with an opening at the top. This opening is used to fill the molten CsA-loaded SNEDDS formulation using a pipette or syringe. The CsA-loaded SNEDDS formulation was characterized by FTIR, DSC and SEM/EDX. The in-vitro release of CsA showed complete release within sixty minutes and followed Korsmeyer-Peppas release kinetics. The drug release was not affected by either the shell opening size or the amount of the loaded formulation. This novel method is simple and straightforward for personalized dosage delivery of drug-loaded SNEDDS formulations.

Assessing the permeability of supersaturating drug delivery system of amorphous drug-polyelectrolyte/protein nanoplexes in Caco-2 cell monolayer

Solubility enhancements of amorphous drug-polyelectrolyte and drug-protein nanoparticle complexes (nanoplexes) by virtue of their supersaturation generation were established previously. Their permeability across intestinal membrane, however, had not been assessed. The present work evaluated the membrane permeability of amorphous drug-polyelectrolyte/drug-protein nanoplexes across Caco-2 cell monolayer in comparison to the native drugs. Ciprofloxacin (CIP)-dextran sulfate (DXT) and curcumin (CUR)-bovine serum albumin (BSA) were used as the model drug-polyelectrolyte and drug-protein nanoplexes, respectively. The permeability was evaluated for aqueous suspension and granules of the nanoplex. The results showed the CIP-DXT nanoplex exhibited higher apical-to-basal permeability and lower efflux ratio than native CIP, hence higher net CIP absorption. The effect of CIP concentration on permeability was insignificant indicating passive diffusion. The CUR-BSA nanoplex exhibited higher permeability than native CUR in both apical-to-basal and basal-to-apical directions caused by weakened Caco-2 cells' tight junctions in the presence of nanoplex. Efflux ratios of the CUR-BSA nanoplex and native CUR were nonetheless similar. Aqueous suspension and granules of the nanoplex exhibited similar permeability profiles attributed to granules’ good aqueous reconstitution. Importantly, both nanoplexes exhibited similar cytotoxicity towards Caco-2 cells as the native drugs, rendering nanoplex a promising formulation approach for solubility and permeability enhancements.

Formulation of silymarin binary and ternary solid dispersions: Characterization, simulation study and cell viability assessment against lung cancer cell line

Silymarin (SL) is a water-insoluble flavonoid used in the treatment of different diseases, but its therapeutic activity is limited due to its low solubility. So, in the present study, SL solid dispersions (SDs) were developed using different carriers like Kollidone VA64 (KL), Soluplus (SP), and Poloxamer 188 (PL) by solvent evaporation (SE), microwave irradiation (MI), and freeze-drying (FD) methods. The phase solubility and saturation solubility studies were assessed to estimate the stability constant as well as the carrier effect. The dissolution studies were performed for prepared SL-SDs (binary and ternary) to select the optimum SL-SDs. The selected SL-SDs (F5, F9) were further characterized for infrared spectroscopy (IR), nuclear magnetic resonance (NMR), differential scanning calorimeter (DSC), scanning electron microscope (SEM), and X-ray diffraction (XRD). Finally, the comparative cell viability assay (lung cancer cell line) was performed to evaluate the change in activity after the formulation of SDs. The phase solubility and solubility study results displayed marked enhancements in solubility. The dissolution study findings showed significant enhancement in drug release from ternary solid dispersions (F7–F9) > ternary physical mixture (PM3) > binary solid dispersions (F1–F6) > binary physical mixture (PM1, PM2) in comparison to free SL. A greater release was observed from ternary SDs due to the addition of PL in the formulation, which had a synergistic effect on increasing the solubility. IR and NMR spectra revealed no chemical interaction between SL, KL, and PL. DSC, XRD, and SEM all confirmed the transformation of crystalline SL into amorphous SL. The cell viability assay demonstrated significantly enhanced results from ternary solid dispersion (F9) compared to free SL. Based on the study results, it can be said that SL-SDs are an alternative way to deliver drugs orally that can improve solubility and have anti-cancer activity.

Effect of Ultrasonic-Assisted Enzymatic Hydrolysis on Functional Properties and Antioxidant Activity of Eri Silkworm Pupa Protein Isolate

Philosamia ricini (Eri silkworm) pupa protein isolate (EPI) was utilized to prepare pupa protein hydrolysate (EPIH) through enzymatic hydrolysis. Additionally, the isolate underwent ultrasonic treatment at 20 kHz to become ultrasound pretreated EPI (EPIU), which was then enzymatically hydrolyzed to obtain ultrasound pretreated protein hydrolysate (EPIUH). The physicochemical properties of these samples were investigated, including molecular weight, solubility, foaming and emulsion properties, water- and oil-holding capacity, antioxidant activity, and color. When compared to EPI (used as the control), EPIU exhibited a high degree of hydrolysis at 20 minutes ( DH = 29.24 % ). At a total process time of 20 minutes, the degree of hydrolysis for EPIH, EPIU, and EPIUH was found to be 13%, 29%, and 41%, respectively. SDS-PAGE analysis indicated no difference in molecular weight between EPI and EPIU (11–75 kDa). However, the molecular weight profiles of EPIH and EPIUH were reduced (8–45 kDa), resulting in changes in protein functionalities. The high DH value contributed to the enhancement of antioxidant activity, solubility, emulsion capacity, emulsion stability, and foam capacity of the protein isolate at pH 7. Furthermore, the ultrasonic pretreatment of the protein hydrolysate increased the lightness of the protein powder by reducing the enzyme activity of the polyphenol oxidase (PPO). These results suggest that ultrasonic pretreatment of the protein hydrolysate could be applied to improve the properties of Eri silkworm pupa protein for use in the food and beverage industry, such as protein-rich beverages or salad dressings.

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.

Microalgae cultivation: from CO2 fixation to single-cell protein production

Bio-sequestration of CO2 using microalgae to recycle CO2 into valuable products such as single-cell proteins (SCP) is one of the most promising fields nowadays. Microalgae are able to use CO2 as their carbon source and subsequently build carbohydrates, proteins, nucleic acids, and lipids. Nevertheless, all microalgae strains do not have the same CO2 tolerance and culture conditions. Moreover, pure CO2 is less soluble in water, which leads to a low carbon capture and fixation rate. Thus, to optimise SCP production in relation to CO2 mitigation, studies of the enhancement of solubilization of CO2 in water as well as the determination of the optimum process parameter for CO2 fixation and SCP production need to be done. Consequently, this study aims to review the cultivation conditions for single-cell protein production.

Estimation of Human Oral Fraction Dose Absorbed of Simvastatin from Various Formulations using in-situ Single Pass Intestinal Perfusion Method

Background: SIM is a poorly water-soluble drug with dissolution-dependent bioavaila-bility. A solid dispersion and self-emulsifying drug delivery system was developed, optimized, and evaluated to improve its bioavailability. The permeability coefficient in rats was determined using the in-situ single-pass intestinal perfusion (SPIP) technique. Further, the permeability coefficient (Peff, humans) was used to calculate the permeability and fraction of SIM bioavailable to humans which have not yet been reported for these formulations. Objective: To estimate and compare various formulations of Simvastatin (SIM) for bioavailable fraction to humans (Fa) as a function of solubility enhancement. Methods: In this study, the preparation and evaluation of SIM formulations i.e., Self-emulsifying drug delivery system (SEDDS) and Solid dispersions (SD) are discussed in brief. An uncomplicat-ed, precise, and accurate HPLC method was validated for simultaneous determination of SIM and phenol red as per ICH guidelines. A comparative in-vitro dissolution test, pharmacokinetic studies, and in-situ SPIP technique in rats were carried out amongst optimized formulations of SIM-SD and SIM-SEDDS, SIM suspension (SIM-SUSP), and SIM marketed preparation (SIM-MP). Results: The HPLC method was successfully validated. In-vitro dissolution test displays that both the SIM formulations i.e., SIM-SEDDS and SIM-SD shows better dissolution rate than SIM-MP and SIM-SUSP. Pharmacokinetic studies revealed that SIM-SEDDS, SIM-SD, and SIM-MP showed significant differences when compared to SIM-SUSP in terms of Cmax, [AUC] 0-∞, at P ≤ 0.05. The comparison of permeability coefficient between SIM SEDDS vs. SIM MP and SIM SEDDS vs. SIM SD were non-significant. In contrast, SIM- SUSP vs. all other formulations were significantly different at P ≤ 0.05 (employing two-way ANOVA followed by post-Bonferroni Test). Fa for SIM SUSP, an optimized formulation of SIM-SEDDS, SIM-MP, and SIM-SD are 0.353, 0.977, 0.975, and 0.987 respectively. It is revealed that SIM-SEDDS and SIM-SD showed enhanced absorption and the results are confirmed by in-vitro data, pharmacokinetic studies, and In-situ SPIP techniques. Conclusion: The permeability prediction method is a rapid and economical method for screening chemical compounds with the least possible utilization of resources. So, its use can be extended in prime and initial screening prototypes for the evaluation of compounds in the early stages of their formulations.

Preparation, characterization, in-vitro and toxicological evaluation of carbopol based nanogels for solubility enhancement of Valsartan

Solubility is an essential criterion for attaining desired concentration of the drug within the systemic circulation to ensure intended pharmacological action. The main setback for the formulation development of new chemical entities and generic drugs is their lower aqueous solubility. Therefore, a drug carrier system is needed which not only enhances the solubility of low aqueous soluble drugs but also maintains a constant pharmacological action of drugs within predetermined intervals of time. For this purpose, authors prepared carbopol 934-co-poly(itaconic acid) (CPcPIA) nanogels by the free radical polymerization technique for the solubility enhancement of Valsartan. The polymeric nanogels were characterized and studied for further evaluation. FTIR studies indicated no interactions between the drug and nanogel contents. SEM showed a porous and sponged structure of particles without any agglomeration. Similarly, higher thermal stability was detected for the fabricated nanogel compared to its constituents, while reduction in crystallinity of the drug and excipients was shown by XRD analysis, indicating the amorphous nature of the polymeric nanogels. Average particle size and zeta potential of prepared nanogels were found 290.32 nm and –8.32 mV, respectively. Furthermore, various studies such as sol-gel fraction, dynamic swelling, drug loading, in-vitro drug release studies, solubility, and toxicity study were conducted for the developed nanogels. A significant increase in the solubility of Valsartan (2.002, 2.976, and 3.543 mg/mL) was observed by polymeric nanogels in pH 1.2, deionized distilled water, and pH 7.4 as compared to reference product. Toxicity study indicated no toxic effect of prepared nanogels on rabbit's species. Thus, it can be demonstrated from the results that synthesized nanogels are not only limited to a specific class of drug but the solubility of all low aqueous soluble drugs can be enhanced by the prepared networks of nanogels.

Performance optimization of acrylonitrile butadiene styrene/thermoplastic polyurethane composite foams blown with carbon dioxide using Taguchi technique

AbstractIn this study, acrylonitrile butadiene styrene (ABS)/thermoplastic polyurethane (TPU) composite foam blown with CO2 was fabricated. Optimization was done by design of experiment (DOE) on the cellular structure using the Taguchi method. Foaming time (20, 40, and 80 s), saturation pressure (4, 5.5, and 7 MPa), and foaming temperature (80, 90, and 120°C) are the input parameters. The results obtained from the signal‐to‐noise (S/N) analysis showed that the most effective factor on the cell density (CD) was the saturation pressure and its influence rate was 48.05%, and also, the CD improved with the increase in the saturation pressure because the high saturation pressure leads to an enhancement in gas solubility and the rate of cell nucleation. Moreover, the foaming temperature and the foaming time had a noteworthy impact on the void fraction and the cell size (CS), and they should be controlled accurately. The impression rate of the foaming time on the CS was 50.86%, and also, with increase in the temperature and the time of foaming, the void fraction showed an increasing trend. The optimal values for the CD, the CS, and the void fraction were predicted to be 1.18 × 109 cells/cm3, 5.37 μm, and 0.5744%, respectively.

Formulation and evaluation of topical gels incorporated with solid dispersions of an antiinflammatory drug

Formulation and development of a most effective product from poorly soluble drugs is one of the most challenging tasks in pharmaceutical industries. Solid dispersion is an efficient solubility enhancement method to overcome the solubility problem. The aim of this study was to formulate topical gels incorporated with solid dispersion of Aceclofenac to enhance permeability through the skin. Aceclofenac solid dispersions were prepared using suitable hydrophilic carriers to increase its aqueous solubility. In this study, solid dispersions of Aceclofenac were prepared by solvent evaporation and co-grinding method with two different hydrophilic carriers such as polyvinyl pyrrolidone (PVPk-30), and HPMC E15 LV. These were used in the ratio of (drug: carrier) 1: 1, 1:2 & 1:3 respectively. Evaluation parameters for formulation optimization were drug content, percentage practical yield, DSC, , in-vitro dissolution studies & FTIR. The optimized SD (F3) solid dispersion is incorporated in topical gels of different concentrations prepared by using two gelling agents such as Carbopol 934 and HPMC K100M. From the results of in-vitro dissolution studies it was found that formulation F3 containing PVP k30 (1 : 3 ratio of drug: PVP k30) shows a higher dissolution rate compared with other formulations and pure drug. Optimized solid dispersion was incorporated into topical gels prepared by using two gelling agents in different concentrations. From the stability data obtained, no significant changes in physical appearance, viscosity, pH, and drug contents were seen. The present research work could be concluded as a successful production of topical gels incorporated with Aceclofenac solid dispersion. Improvement in aqueous solubility and thereby greater skin permeation is expected

A novel formulation of ketoconazole entrapped in alginate with anionic polymer beads for solubility enhancement: Preparation and characterization

Ketoconazole has low solubility in intestinal pH, whereas drug absorption is largest in the small intestine, which can reduce the bioavailability of the drug. Alginate can be combined with a suitable polymer and cross-linked with divalent ions and another polymer to enhance the solubility of the drug. Ketoconazole could be loaded into a matrix polymer consisting of alginate and anionic polymer through hydrogen bonds formed with the N atom of the ketoconazole. The method employed to produce ketoconazole beads involved ionic gelation with CaCl2 as a cross- linking agent, and various polymer combinations were used: alginate 100:0 (AL100), alginate:pectin 75:25 (AP75) and 50:50 (AP50), alginate:gum acacia 75:25 (AG75) and 50:50 (AG50), and alginate:carrageenan 75:25 (AK75) and 50:50 (AK50). The beads were characterized by using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), X-ray diffraction (XRD), swelling study, in vitro drug release study, and solubility determination. The incorporation of ketoconazole into combination matrices of AL100, AG75, AP75, AP50, and AK75 resulted in significantly higher solubility in FaSSIF-2X (Fasted State Simulated Intestinal Fluid) at pH 6.5 compared to pure ketoconazole.

Impact of polyethylene glycol molar mass and structural isomer of alcohol on the solubility and dissolution enhancement of mesalazine

This work reports the solubility of mesalazine (5-ASA) in mole fraction terms (x1,T) in mono-solvents of polyethylene glycol (PEG) 400, 1-propanol and 2-propanol along with their binary mixtures in different mass fractions of PEG 400 at 293.15–313.15 K and atmospheric pressure which measured experimentally by a shake-flask technique. The solubility of 5-ASA in these mixtures not only enhances with enhancing temperature, but also raises with raising PEG's mass fraction. Effect of PEG molar mass on the solubility of 5-ASA was also estimated by measuring its solubility in PEG 200 or 600 + 1- or 2-propanol mixtures at 298.15 K. Upon the same temperature and mass fraction of PEGs, the upward trend of 5-ASA mole fractions was: PEG 600 + 1-propanol > PEG 600 + 2-propanol > PEG 400 + 1-propanol > PEG 400 + 2-propanol > PEG 200 + 1-propanol > PEG 200 + 2-propanol indicating, the binary mixtures containing a high molar mass of PEG and 1-propanol with a hydroxyl group attached to carbon number 1 had a more solubilization power. Then, the experimental mole fractions were modelled by some cosolvency and activity coefficient models, and the model parameters were regressed. The back-computed mole fractions of 5-ASA by cosolvency models presented a better agreement with the experimental data than that of activity models and Jouyban-Acree model had the best performance (low overall average percentage deviation of 6.1 %). By means of enthalpy-entropy compensation analysis, non-linear ΔsolH° against ΔsolG° compensation plots with positive and negative slopes were achieved as a consequent of increasing 5-ASA solvation by PEG molecules and the solvent-structure loosing, respectively.

A Review of Hydrotropic Solubilization Techniques for Enhancing the Bioavailability of Poorly Soluble Drugs.

Hydrotropic solubilization is a technique that can be used to improve the solubility of drugs that are poorly soluble. This technique involves adding a large amount of a second solute, known as a hydrotrope, which increases the aqueous solubility of the poorly soluble drug. Hydrotropes such as sodium citrate, sodium benzoate, and urea have been shown to be effective in enhancing the solubility of poorly soluble drugs. This technique has several advantages over other solubility enhancement techniques, including its cost-effectiveness, eco-friendliness, and the fact that it does not require chemical modification of hydrophobic drugs or the use of organic solvents. Hydrotropic agents are now being used to develop various dosage forms, including solid dispersions, mouth-dissolving tablets, and injections, to improve poorly water-soluble drugs' therapeutic effectiveness and bioavailability. This review paper will provide an overview of hydrotropic solubilization techniques.

Microwave Generated Nanocomposites for Solubility Enhancement

Nanocomposites is technique used for solubility enhancement. Macro particle are breaking down in micro Nano particle by different technique. Nanocomposites, a high performance material exhibit unusual property combinations and unique design possibilities. With an estimated annual growth rate of about 25% and fastest demand to be in engineering plastics and elastomers, their potential is so striking that they are useful in several areas ranging from packaging to biomedical applications. In this review article we will discuss about solubility enhancement technique like nanocomposite. We will overview about nanocomposite, type of Nanocomposites, method of preparation, advantages, disadvantages, application of nanocomposites.

Self-emulsifying drug delivery systems (SEDDS) disrupt the gut microbiota and trigger an intestinal inflammatory response in rats

Self-emulsifying drug delivery systems (i.e. SEDDS, SMEDDS and SNEDDS) are widely employed as solubility and bioavailability enhancing formulation strategies for poorly water-soluble drugs. Despite the capacity for SEDDS to effectively facilitate oral drug absorption, tolerability concerns exist due to the capacity for high concentrations of surfactants (typically present within SEDDS) to induce gastrointestinal toxicity and mucosal irritation. With new knowledge surrounding the role of the gut microbiota in modulating intestinal inflammation and mucosal injury, there is a clear need to determine the impact of SEDDS on the gut microbiota. The current study is the first of its kind to demonstrate the detrimental impact of SEDDS on the gut microbiota of Sprague-Dawley rats, following daily oral administration (100 mg/kg) for 21 days. SEDDS comprising a lipid phase (i.e. Type I, II and III formulations according to the Lipid Formulation Classification Scheme) induced significant changes to the composition and diversity of the gut microbiota, evidenced through a reduction in operational taxonomic units (OTUs) and alpha diversity (Shannon’s index), along with statistically significant shifts in beta diversity (according to PERMANOVA of multi-dimensional Bray-Curtis plots). Key signatures of gut microbiota dysbiosis correlated with the increased expression of pro-inflammatory cytokines within the jejunum, while mucosal injury was characterised by significant reductions in plasma citrulline levels, a validated biomarker of enterocyte mass and mucosal barrier integrity. These findings have potential clinical ramifications for chronically administered drugs that are formulated with SEDDS and stresses the need for further studies that investigate dose-dependent effects of SEDDS on the gastrointestinal microenvironment in a clinical setting.