Controlled Molecular Arrangement of Cinnamic Acid in Layered Double Hydroxide through pi-pi Interaction for Controlled Release.

Cinnamic acid (CA) was successfully incorporated into Zn-Al layered double hydroxide (LDH) through coprecipitation. The CA moiety was stabilized in the interlayer space through not only electrostatic interaction but also intermolecular π-π interaction. It was noteworthy that the CA arrangement was fairly independent of the charge density of LDH, showing the important role of the layer-CA and CA-CA interactions in molecular stabilization. Computer simulations using the Monte Carlo method as well as analytical approaches including infrared, UV-vis spectroscopy, and differential scanning calorimetry showed the existence of intermolecular interaction. In order to reinforce molecular stabilization, a neutral derivative of CA, cinnamaldehyde (CAD), was additionally incorporated into LDH. It was clearly shown that CAD played a role as a π-π interaction mediator to enhance the stabilization of CA. The time-dependent release of CA from LDH was first governed by the layer charge density of LDH; however, the existence of CAD provided additional stabilization to the CA arrangement to slow down the release kinetics.

Identification and quantification techniques of polymorphic forms - A review.

In the pharmaceutical industry, the unexpected appearance of crystalline forms could impact the therapeutic efficacy of an Active Pharmaceutical Ingredient (API). For quality control, a thorough qualitative and quantitative monitoring of pharmaceutical solid forms is essential to ensure the detection and the quantification of crystalline forms, wither different or with the same chemical composition (polymorphs) at a low detection level. The purpose of this paper was to review and highlight the importance of choosing adequate solid-state techniques for detection and quantification APIs that present polymorphism - based on limits of detection (LOD) and quantification (LOQ), pharmacopeias specifications, international guidelines and studies reported in the literature. To this study, the powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Infrared and Raman spectroscopies and solid-state nuclear magnetic resonance (NMR) were the solid-state techniques analyzed. Additionally, the Argentine, Brazilian, British, European, International, Japanese, Mexican and the United States of America pharmacopeias were reviewed. Based on the analysis performed, the advantages and disadvantages of these techniques, as well as the LOD and LOQ values of APIs were reported. In comparison to these solid-state techniques, reference material used for identification analyses should be previously identified with the corresponding polymorph. Without this previous procedure, the patterns, the spectra, and DSC curves of the reference material can only be used to confirm the mixture of solid forms, not being able to specify which polymorphs are contained in the sample. A major advantage of PXRD is the use of the calculated diffraction patterns obtained from the Crystallographic Information Frameworks (CIFs) files which could be used as a reference pattern without any other information, assistance technique, or physical standards. Regarding the quantification aspect, different pharmacopeias suggest various methods such as the PXRD combining with Rietveld method, which can be used to obtain lower LOD values for minority phases in the mixture of different substances without the need for a calibration curve. Raman spectroscopy can detect polymorphs in small particles and solid-state NMR spectroscopy is a powerful technique for quantification not only crystalline but also crystalline-amorphous mixtures. Finally, this review intends to be a useful tool to control, with efficiency and accuracy, the polymorphism of APIs in pharmaceutical compounds.

Continuous Synthesis of Cinnarizine Salt with Malic Acid by Applying Green Chemistry Using Water-Assisted Twin Screw Extrusion.

Organic solvent-free process or green chemistry is needed for manufacturing pharmaceutical salts to avoid various environmental, safety, and manufacturing cost issues involved. In this study, a cinnarizine (CNZ) salt with malic acid at a 1:1 molar ratio was successfully prepared by twin screw extrusion (TSE) with water assistance. The feasibility of salt formation was first evaluated by screening several carboxylic acids by neat grinding (NG) and liquid-assisted grinding (LAG) using a mortar and pestle, which indicated that malic acid and succinic acid could form salts with CNZ. Further studies on salt formation were conducted using malic acid. The examination by hot-stage microscopy revealed that the addition of water could facilitate the formation and crystallization of CNZ-malic acid salt even though CNZ is poorly water-soluble. The feasibility of salt formation was confirmed by determining the pH-solubility relationship between CNZ and malic acid, where a pHmax of 2.7 and a salt solubility of 2.47 mg/mL were observed. Authentic salt crystals were prepared by solution crystallization from organic solvents for examining crystal properties and structure by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared (FTIR) spectroscopy, solid-state 13C and 15N nuclear magnetic resonance (NMR), and single-crystal X-ray diffraction (SXD). These techniques also established that a salt, and not a cocrystal, was indeed formed. The CNZ salt crystals were then prepared by TSE of a 1:1 CNZ-malic acid mixture, where the addition of small amounts of water resulted in a complete conversion of the mixture into the salt form. The salts prepared by solvent crystallization and water-assisted TSE had identical properties, and their moisture sorption profiles were also similar, indicating that TSE is a viable method for salt preparation by green chemistry. Since TSE can be conducted in a continuous manner, the results of the present investigation, if combined with other continuous processes, suggest the possibility of continuous manufacturing of drug products from the synthesis of active pharmaceutical ingredients (APIs) to the production of final dosage forms.

A rapid solid form risk assessment workflow for ophthalmic drug candidates.

OBJECTIVE: This work introduces a material-sparing process that rapidly screens the solid form landscape for ophthalmic compound candidates. SIGNIFICANCE: Crystalline form of compound candidates generated by a Form Risk Assessment (FRA) can be used to reduce their downstream development risk. METHODS: This workflow evaluated nine model compounds with various molecular and polymorphic profiles by using less than 350 mg of drug substances. Kinetic solubility of the model compounds in a variety of solvents was screened to support the experimental design. The FRA workflow integrated several crystallization methods such as temperature-cycled slurrying (thermocycling), cooling, and evaporation. The FRA was also applied on ten ophthalmic compound candidates for verification. X-ray powder diffractometry (XRPD) was used for form identification. RESULTS: For the nine model compounds studied, multiple crystalline forms were generated. This demonstrates the potential of the FRA workflow to reveal polymorphic tendency. In addition, thermocycling process was found to be the most effective technique to capture the thermodynamically most stable form. Satisfactory results were observed with the discovery compounds intended for ophthalmic formulations. CONCLUSIONS: This work introduces a form risk assessment workflow by using sub-gram level of drug substances. The capability of this material-sparing workflow to discover polymorphs and capture the thermodynamically most stable forms within 2-3 weeks makes it suitable for discovery stage compounds, especially for ophthalmic candidates.

Design of mirtazapine solid dispersion with different carriers' systems: optimization, in vitro evaluation, and bioavailability assessment.

The solid dispersion technique is the most effective and widely used approach for increasing the solubility and release of drugs that have low water solubility. Mirtazapine (MRT) is an atypical antidepressant used to treat severe depression. MRT has a low oral bioavailability (about 50%) due to its low water solubility (BCS class II). The study's goal was to determine optimum conditions for incorporating MRT into various polymer types utilizing the solid dispersion (SD) technique, with the goal of selecting the most suitable formula with the optimal aqueous solubility, loading efficiency, and dissolution rate. The D-optimal design was used to pick the optimal response. The optimum formula was subjected to physicochemical evaluation by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM). In vivo bioavailability study was conducted on white rabbits' plasma samples. MRT-SDs were prepared by the solvent evaporation method using Eudragit (RL-100, RS-100, E-100, L-100-55), PVP K-30, and PEG 4000 with different drug/polymer percentages (33.33%, 49.99%, and 66.66%). Results showed that the optimum formula obtained using PVP K-30 at a drug percentage of 33.33% gave a loading efficiency of 100.93%, an aqueous solubility of 0.145 mg/ml, and a dissolution rate of 98.12% after 30 min. These findings demonstrated promising enhancement of MRT properties and increasing its oral bioavailability by 1.34-fold more than plain drug.

Long-Term In Vitro Assessment of Biodegradable Radiopaque Composites for Fiducial Marker Fabrication.

Biodegradable polymer-based composite materials may be successfully utilised to fabricate fiducial markers (FMs), which are intended to precisely label tumour margins during image-guided surgery or radiotherapy. However, due to matrix degradability, the stability of the functional properties of FMs depends on the chosen polymer. Thus, this study aimed to investigate novel radiopaque composites which varied in the polymeric matrix-polycaprolactone (PCL), poly(L-lactide-co-caprolactone) (P[LAcoCL]) with two molar ratios (70:30 and 85:15), and poly(L-lactide-co-glycolide) (with molar ratio 82:18). The radiopaque component of the materials was a mixture of barium sulphate and hydroxyapatite. The changes in water contact angle, stiffness, and radiopacity occurring during the 24-week-long degradation experiment were examined for the first time. This study comprehensively analyses the microstructural causes of composites behaviour within degradation experiments using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), gel permitted chromatography (GPC), and scanning electron microscopy (SEM). The obtained results suggest that the utilized biodegradable matrix plays an essential role in radiopaque composite properties and stability thereof. This long-term in vitro assessment enabled a comparison of the materials and aided in choosing the most favourable composite for FMs' fabrication.

Authenticity Assessment from Sesame Seeds to Oil and Sesame Products of Various Origin by Differential Scanning Calorimetry.

The aim of this study was to conduct thermal characterization of sesame seeds and oils from various geographical origins (Ethiopia, India, Nigeria, Sudan, Turkey), different method of extraction (hexane and cold-pressing), and different types of derived products (halva and tahini). Thermal characterization was investigated using differential scanning calorimetry (DSC), which showed that origin of the seeds has no influence on the melting profile of sesame oil (peak temperature and enthalpy). Method of extraction (hexane and cold-pressing) influenced the peak temperatures of the resulting oils (p ≤ 0.05). The addition of 20% of palm olein to pure sesame oil influenced the significant changes in thermodynamic parameters such as peak temperature (Tm2), which was lowered from −5.89 °C to −4.99 °C, peak half width (T1/2), elevated from 3.01 °C to 4.52 °C, and the percentage of first peak area (% peak 1) lowered from 87.9 to 73.2% (p ≤ 0.05). The PCA method enabled to distinguish authentic and adulterated sesame oils of various origins. There were no significant differences in thermal properties among the products (halva, tahini) and the authentic sesame oil (p > 0.05). The obtained results showed DSC feasibility to characterize sesame oil and sesame products in terms of authenticity.

Structural Investigation of Hesperetin-7-O-Glucoside Inclusion Complex with ß-Cyclodextrin: A Spectroscopic Assessment.

Flavonoids are biologically active natural products of great interest for their potential applications in functional foods and pharmaceuticals. A hesperetin-7-O-glucoside inclusion complex with ß-cyclodextrin (HEPT7G/ßCD; SunActive® HCD) was formulated via the controlled enzymatic hydrolysis of hesperidin with naringinase enzyme. The conversion rate was nearly 98%, estimated using high-performance liquid chromatography analysis. The objective of this study was to investigate the stability, solubility, and spectroscopic features of the HEPT7G/ßCD inclusion complex using Fourier-transform infrared (FTIR), Raman, ultraviolet-visible absorption (UV-vis), 1H- and 13C- nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), liquid chromatography/mass spectroscopy (LC-MS), scanning electron microscopy (SEM), and powdered X-ray diffraction (PXRD) spectroscopic techniques including zeta potential, Job's plot, and phase solubility measurements. The effects of complexation on the profiles of supramolecular interactions in analytic features, especially the chemical shifts of ß-CD protons in the presence of the HEPT7G moiety, were evaluated. The stoichiometric ratio, stability, and solubility constants (binding affinity) describe the extent of complexation of a soluble complex in 1:1 stoichiometry that exhibits a greater affinity and fits better into the ß-CD inner cavity. The NMR spectroscopy results identified two different configurations of the HEPT7G moiety and revealed that the HEPT7G/ßCD inclusion complex has both -2S and -2R stereoisomers of hesperetin-7-O-glucoside possibly in the -2S/-2R epimeric ratio of 1/1.43 (i.e., -2S: 41.1% and -2R: 58.9%). The study indicated that encapsulation of the HEPT7G moiety in ß-CD is complete inclusion, wherein both ends of HEPT7G are included in the ß-CD inner hydrophobic cavity. The results showed that the water solubility and thermal stability of HEPT7G were apparently increased in the inclusion complex with ß-CD. This could potentially lead to increased bioavailability of HEPT7G and enhanced health benefits of this flavonoid.

DSC, FT-IR and NIR with Chemometric Assessment Using PCA and HCA for Estimation of the Chemical Stability of Oral Antidiabetic Drug Linagliptin in the Presence of Pharmaceutical Excipients.

Pharmaceutical excipients should not interact with active substances, however, in practice, they sometimes do it, affecting the efficacy, stability and safety of drugs. Thus, interactions between active substances and excipients are not desirable. For this reason, two component mixtures of oral antidiabetic drug linagliptin (LINA) with four excipients of different reactivity, i.e., lactose (LAC), mannitol (MAN), magnesium stearate (MGS) and polyvinylpyrrolidone (PVP), were prepared in a solid state. A high temperature and a high humidity of 60 °C and 70% RH, respectively, were applied as stressors in order to accelerate the potential interactions between LINA and excipients. Differential scanning calorimetry (DSC) as well as Fourier transform infrared (FT-IR) and near infrared (NIR) spectroscopy were used to estimate the changes due to potential interactions. In addition, chemometric computation of the data with principal component analysis (PCA) and hierarchical cluster analysis (HCA) was applied to adequately interpret the findings. Of the excipients used in the present experiment, all of them were not inert in relation to LINA. Some of the interactions were shown without any stressing, whereas others were observed under high-temperature/high-humidity conditions. Thus, it could be concluded that selection of appropriate excipients for LINA is very important question to minimize its degradation, especially when new types of formulations with LINA are being developed and manufactured.

Candelilla Wax Extracted by Traditional Method and an Ecofriendly Process: Assessment of Its Chemical, Structural and Thermal Properties.

A comparative study was carried out on the chemical, structural and thermal properties of candelilla wax from four wax-producing communities in Mexico, which was obtained by two extraction processes, the conventional one using sulfuric acid (SA) and an eco-friendly alternative process using citric acid (CA) as the extracting agent. The waxes were analyzed by basic chemistry (acidity, saponification, ester indexes, and others), color, Fourier transform infrared spectroscopy (FTIR), Raman micro-spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and hardness and brittleness measurements. The waxes obtained by the environmentally friendly process showed differences in their physicochemical properties when compared to waxes from the conventional process. In addition, they showed some improvements, such as lighter shades and harder waxes, suggesting that the new environmentally friendly process is a viable option.

Optimization of mirtazapine loaded into mesoporous silica nanostructures via Box-Behnken design: in-vitro characterization and in-vivo assessment.

Employment of mesoporous silica nanostructures (MSNs) in the drug delivery field has shown a significant potential for improving the oral delivery of active pharmaceutical products with low solubility in water. Mirtazapine (MRT) is a tetracyclic antidepressant with poor water solubility (BCS Class II), which was recently approved as a potent drug used to treat severe depression. The principle of this research is to optimize the incorporation of Mirtazapine into MSNs to improve its aqueous solubility, loading efficiency, release performance, and subsequent bioavailability. The formulation was optimized by using of Box-Behnken Design, which allows simultaneous estimation of the impact of different types of silica (SBA-15, MCM-41, and Aluminate-MCM-41), a different drug to silica ratios (33.33%, 49.99%, and 66.66%), and different drug loading procedures (Incipient wetness, solvent evaporation, and solvent impregnation) on the MRT loading efficiency, aqueous solubility and dissolution rate. The optimized formula was achieved by loading MRT into SBA-15 at 33.33% drug ratio prepared by the incipient wetness method, which displayed a loading efficiency of 104.05%, water solubility of 0.2 mg/ml, and 100% dissolution rate after 30 min. The pharmacokinetic profile of the optimized formula was obtained by conducting the in-vivo study in rabbits which showed a marked improvement (2.14-fold) in oral bioavailability greater than plain MRT. The physicochemical parameters and morphology of the optimized formula were characterized by; gas adsorption manometry, scanning electron microscopy (SEM), polarized light microscopy (PLM), Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD).

Formulation and Optimization of Diclofenac Sodium Loaded Ethylcellulose Nanoparticles

Abstract Design of experiment (DoE) is a useful time and cost-effective tool for analyzing the effect of independent variables on the formulation characteristics. The aim of this study is to evaluate the effect of the process variables on the characteristics involved in the preparation of Diclofenac Sodium (DC) loaded ethylcellulose (EC) nanoparticles (NP) using Central Composite Design (CCD). NP were prepared by W/O/W emulsion solvent evaporation method. Three factors were investigated (DC/EC mass ratio, PVA concentration, homogenization speed) in order to optimize the entrapment efficiency (EE) and the particle size of NP. The optimal formulation was characterized by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and in vitro release. Optimized formulation showed an EE of 49.09 % and an average particle size of 226.83 nm with a polydispersity index of 0.271. No drug-polymer interaction was observed in FTIR and DSC analysis. SEM images showed that the particles are spherical and uniform. The in vitro release study showed a sustained release nature, 53.98 % of the encapsulated drug has been released over 24hours period. This study demonstrated that statistical experimental design methodology can optimize the formulation and the process variables to achieve favorable responses.

Structural assessment of the bioplastic (poly-3-hydroxybutyrate) produced by Bacillus flexus Azu-A2 through cheese whey valorization.

The demand for the production of biodegradable plastics has significantly increased. Bioplastics have become an essential alternative to the threats of the daily consumable plastics, sourced from fossil fuels, to the environment. Polyhydroxyalkonates (PHAs) are a ubiquitous group of bioderived and biodegradable plastics, however their production is limited by the costs associated mainly with the carbon sources. Herein, this study aims to reduce the PHAs production cost by using a by-product from the dairy industry, i.e., cheese whey (CW), as a sole carbon source. The developed process recruits an aquatic isolate, Bacillus flexus Azu-A2, and is optimized via studying various parameters using the shaking flasks technique. The results showed that the maximum PHA production (0.95 g L-1) and PHA content (20.96%, w/w), were obtained after incubation period 72 h at 45 °C, 100 rpm agitation rate, 50% CWS concentration, pH 8.5, and 1.0 g L-1 ammonium chloride. Physiochemically, Fourier transform infrared spectroscopy (FTIR), gas chromatography-mass spectroscopy (GC-MS), nuclear magnetic resonance (NMR), and energy-dispersive X-ray (EDX) techniques, emphasized the type of the extracted PHA as polyhydroxybutyrate (PHB). The thermal properties of PHB were measured using differential scanning calorimetry (DSC), recording melting transition temperature (Tm) at 170.96 °C. Furthermore, a scanning electron microscope (SEM) visualized a homogenous microporous structure for the thin PHB biofilm. In essence, this study highlights the ability of Bacillus flexus Azu-A2 to produce a good yield of highly purified PHB at reduced production cost from dairy CW. Consequently, the current study paves the way for an improved whey management strategy.

Application of MCR-ALS with EFA on FT-IR spectra of lipid bilayers in the assessment of phase transition temperatures: Potential for discernment of coupled events.

Temperature-dependent transmission FT-IR spectroscopy and DSC measurements were conducted on lipid multibilayers constituted from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine. Lipid multibilayers made from 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, which do not form a ripple phase, were examined as a reference. Spectra were analyzed using multivariate curve resolution technique with alternating least squares and evolving factor analysis (MCR-ALS with EFA) and lipid phase transition temperatures were determined. Polar parts of lipid molecules exert greater response on a ripple phase formation than non-polar ones. However, vibrational signatures of hydrocarbon chains with intramolecular origins display certain qualitative differences that pave the way for future work oriented on uncoupling the events that drive ripple phase formation.

Physicochemical features assessment of acemannan-based ternary blended films for biomedical purposes.

The exploitation of natural origin macromolecules, as complex physical mixtures or drugs, increases in biomedical or tissue engineering (TE) solutions. Aloe Vera is a highly explored medicinal plant, from which the main polysaccharide is acemannan (ACE). The ACE combination with chitosan and alginate results in interactions that lead to mixed junction zones formation, predicting membrane functionality improvement. This work proposes the development and characterization of ACE-based blended films as a promising strategy to design a nature-derived bioactive platform. The results confirmed that stable complex polyelectrolyte structures were formed through different intermolecular interactions. The films present good dimensional stability, flexibility, an adequate swelling ability with mostly radial water uptake, and a sustainable ACE release to the medium. Positive biological performance of the ACE-based blended films with L929 cells also suggested that they can be applied in TE solutions, with the potential to act as bioactive topical platforms.

Solid self-microemulsifying nutraceutical delivery system for hesperidin using quality by design: assessment of biopharmaceutical attributes and shelf-life.

AIM: The present study endeavours to develop a solid self-microemulsifying nutraceutical drug delivery system for hesperidin (HES) using quality by design (QbD) to improve its biopharmaceutical attributes. METHODS: A 32 full factorial design was employed to study the influence of factors on selected responses. Risk assessment was performed by portraying Ishikawa fishbone diagram and failure mode effect analysis (FMEA). The in vivo antidiabetic study was carried on induced diabetic rats. RESULTS: The optimised liquid SMEDDS-HES (OF) formulation showed emulsification time (Y 1) = 102.5 ± 2.52 s, globule size (Y 2) = 225.2 ± 3.40 nm, polydispersity index (Y 3) = 0.294 ± 0.62, and zeta potential (Y 4) = -25.4 ± 1.74 mV, respectively. The solid SMEDDS-HES (SOF-7) formulation was characterised by FTIR, PXRD, DSC, and SEM. The shelf life of SOF-7 was found to be 32.88 months. The heamatological and histopathological data of diabetic rats showed prominent antidiabetic activity. CONCLUSIONS: The optimised formulation showed improved dissolution, desired stability, and promising antidiabetic activity.

Towards Volatile Organoselenium Compounds with Cost-Effective Synthesis.

The current portfolio of organoselenium compounds applicable as volatile precursors for atomic layer deposition can be denoted as very limited. Hence, we report herein facile and cost-effective preparation of two bis(trialkylstannyl)selenides as well as one selenole and three bis(trialkylsilyl)selenides. Their syntheses have been optimized to: (i) use readily available and inexpensive starting materials, (ii) involve operationally simple methodology (heating in a pressure vessel), (iii) use a minimum amount of additives and catalysts, and (iv) either exclude additional purification or involve only simple distillation. The chemical structure of prepared Se derivatives was confirmed by multinuclear NMR and GC/MS. Their fundamental thermal properties were investigated by differential scanning calorimetry (DSC) and TGA methods that revealed thermal stability within the range of 160-300 °C.

Chondroitin/dermatan sulfate purified from corb (Sciaena umbra) skin and bone: In vivo assessment of anticoagulant activity.

The present work deals with the extraction and purification of chondroitin sulfate/dermatan sulfate from skin (CSG) and bone (CBG) of corb (Sciaena umbra). Electrophoresis of these polymers in barium acetate buffer on cellulose acetate revealed two fractions similar to dermatan sulfate and chondroitin sulfate. The in vivo anticoagulant activity of both chondroitin sulfate/dermatan sulfate (CS/DS) were evaluated, at 25 and 75 mg kg-1 of body weight (b.w), using activated partial thromboplastin time (aPTT), prothrombine time (TT) and thrombin time (PT) tests. Results showed that aPTT of CSG and CBG at 75 mg kg-1 of b.w were prolonged by 1.59 and 1.48-fold respectively, compared with the control. Further, toxicity studies on liver performed by the catalytic activity of transaminases in plasma, oxidative stress markers and hepatic morphological changes demonstrated that CSG and CBG at both doses are not toxics. In summary, the higher activity and lower toxicity of both CS/DS, especially at 25 mg kg-1 of b.w, recommended these compounds as a better drug candidate.

Stimulatory Effects of Soluplus® on Flufenamic Acid ß-Cyclodextrin Supramolecular Complex: Physicochemical Characterization and Pre-clinical Anti-inflammatory Assessment.

The present study demonstrates the solubility and dissolution of flufenamic acid (FLF)/ß-cyclodextrin (ß-CD)/Soluplus® supramolecular ternary inclusion complex. The binary and ternary inclusion complexes were prepared using solvent evaporation and the microwave irradiation method. The prepared inclusion complexes were evaluated for physicochemical characterization and anti-inflammatory activity using a murine paw edema mol. The phase solubility studies demonstrated 4.59-fold and 17.54-fold enhancements in FLF solubility with ß-CD alone and ß-CD:Soluplus® combination compared with pure FLF, respectively. The in vitro drug release results revealed a significant improvement (P < 0.05) in the release pattern compared with pure FLF. Maximum release was found with flufenamic acid binary and ternary complexes prepared using the microwave irradiation method, i.e., 75.23 ± 3.12% and 95.36 ± 3.23% in 60 min, respectively. The physicochemical characterization results showed complex formation and conversion of the crystalline form of FLF to an amorphous form. The SEM study revealed the presence of a more agglomerated and amorphous structure of the solid particles, which confirmed the formation of complexes. The anti-inflammatory effect of the complex was higher than pure FLF. Therefore, the FLF:ß-CD:Soluplus® inclusion complex may be a very valuable formulation with improved solubility, dissolution, and anti-inflammatory effect.

Oral Bioavailability Enhancement and Anti-Fatigue Assessment of the Andrographolide Loaded Solid Dispersion.

Andrographolide (AG), a major diterpene lactone isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae), possesses a wide spectrum of biological activities. However, its poor water solubility and low bioavailability limit its clinical application. Therefore, this study aimed to develop a solid dispersion (SD) formulation to increase the aqueous solubility and dissolution rate of AG. Different drug-polymer ratios were used to prepare various SDs. The optimized formulation was characterized for differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. The analysis indicated that the optimized SD enhanced AG solubility and dissolution rates by changing AG crystallinity to an amorphous state. The dissolution behaviors of the optimum SD composed of an AG-polyvinylpyrrolidone K30-Kolliphor EL ratio of 1:7:1 (w/w/w) resulted in the highest accumulated dissolution (approximately 80%). Pharmacokinetic studies revealed that Cmax/dose and the AUC/dose increased by 3.7-fold and 3.0-fold, respectively, compared with AG suspension. Furthermore, pretreatment using the optimized AG-SD significantly increased the swimming time to exhaustion by 1.7-fold and decreased the plasma ammonia level by 71.5%, compared with the vehicle group. In conclusion, the optimized AG-SD formulation appeared to effectively improve its dissolution rate and oral bioavailability. Moreover, the optimized AG-SD provides a promising treatment against physical fatigue.