Hydroxypropyl-beta-cyclodextrin Research Articles

Maternal Injection with Dexamethasone Results in Female-Biased Autonomic Dysregulation in Rat Offspring

Autonomic dysfunction is an underlying risk factor for cardiovascular disease (CVD). Maternal injection of the synthetic GC dexamethasone (DEX) during the last 4 days of gestation results in female-biased increases in stress-responsive pressor (MAP), heart rate (HR) and altered heart rate variability (HRV) in adult rat offspring, suggesting a role for GC-mediated programming of autonomic function. The present study used pharmacological antagonists for adrenergic (SYM) or cholinergic (PS) receptors to investigate the degree to which changes in SYM or PS activity underlie the autonomic dysfunction in offspring of dams injected with DEX during late gestation. Naïve breeders were injected with DEX (0.4mg/kg/day, s.c.) or vehicle (hydroxypropyl beta cyclodextrin; Veh) on gestation days 18-21. Radiotelemetry was used in adult offspring for recording HR, MAP, and HRV (root mean square of successive differences: RMSSD). At 10-11 weeks rats were randomly assigned to receive SYM antagonists, α-adrenoceptor (prazosin; 0.5mg/kg, i.p.) + β-adrenoceptor (atenolol; 1mg/kg, i.p.), a PS antagonist (homatropine methylbromide; 0.2mg/kg, i.p), or saline (SAL, i.p.). Evaluations were made over 20 min following injection and then during a 20 min restraint. Females were tested on diestrus. In utero DEX exposure resulted in significantly lower RMSSD, an index of vagal tone, in DEX-exposed females and males. PS blockade significantly reduced RMSSD in Veh-, but not DEX-exposed female offspring. SYM blockade did not influence RMSSD in females. In males, PS blockade reduced in RMSSD in both DEX- and Veh-exposed offspring. SYM blockade only reduced RMSSD in males exposed to DEX. Area under the curve (AUC) analysis revealed that in female offspring, SYM blockade resulted in a greater reduction in HR in DEX-exposed offspring, compared to Veh (DEX-SYM: −220 bpm vs. DEX-SAL; Veh-SYM: −197 bpm vs. VEH-SAL) and during restraint (DEX-SYM: −535 bpm vs. DEX-SAL; Veh-SYM: −342 bpm vs. VEH-SAL). PS blockade resulted in a greater increase in HR in Veh-exposed females both following the injection (Veh-PS: −187 bpm vs. VEH-SAL; DEX-PS: −101 bpm vs. DEX-SAL) and during restraint (Veh-PS: −161 bpm vs. VEH-SAL; DEX-PS: −61 bpm vs. DEX-SAL). AUC analysis for MAP showed similar responses to those for HR with SYM blockade having a greater impact in DEX-exposed females and PS blockade having a greater effect in Veh-exposed females. By contrast, in male offspring in utero DEX exposure did not influence HR or MAP responses to SYM or PS blockade. Overall, these findings suggest that maternal DEX injections alter autonomic development primarily in in female offspring and is characterized by a shift from PS to SYM predominance. Better understanding of the mechanisms involved in this programming are important for identifying individuals at risk for CVD and development of interventional strategies for prevention of CVD. Funding: NIH U54 MH118919. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Boosting antimicrobial potency: Micro encapsulated polymyxin in hydroxypropyl beta cyclodextrin ‘sugar cage’ and alginate via spray drying with coating

Boosting antimicrobial potency: Micro encapsulated polymyxin in hydroxypropyl beta cyclodextrin ‘sugar cage’ and alginate via spray drying with coating

Investigation on the Combined Effect of Hydroxypropyl Beta-Cyclodextrin (HPβCD) and Polysorbate in Monoclonal Antibody Formulation.

Monoclonal antibodies require careful formulation due to their inherent stability limitations. Polysorbates are commonly used to stabilize mAbs, but they are prone to degradation, which results in unwanted impurities. KLEPTOSE® HPβCD (hydroxypropyl beta-cyclodextrin) has functioned as a stable stabilizer for protein formulations in our previous research. The current study investigates the collaborative impact of combining polysorbates and HPβCD as excipients in protein formulations. The introduction of HPβCD in formulations showed it considerably reduced aggregation in two model proteins, bevacizumab and ipilimumab, following exposure to various stress conditions. The diffusion interaction parameter revealed a reduction in protein-protein interactions by HPβCD. In bevacizumab formulations, the subvisible particle counts per 0.4 mL of samples in commercial formulations vs. formulations containing both HPβCD and polysorbates subjected to distinct stressors were as follows: agitation, 87,308 particles vs. 15,350 particles; light, 25,492 particles vs. 6765 particles; and heat, 1775 particles vs. 460 particles. Isothermal titration calorimetry (ITC) measurement indicated a weak interaction between PS 80 and HPβCD, with a KD value of 74.7 ± 7.5 µM and binding sites of 5 × 10-3. Surface tension measurements illustrated that HPβCD enhanced the surface activity of polysorbates. The study suggests that combining these excipients can improve mAb stability in formulations, offering an alternative for the biopharmaceutical industry.

Solubility and Dissolution Enhancement of Candesartan Cilexetil by Complexation with Cyclodextrin

At present, numerous novel chemical compounds face challenges related to their limited solubility in aqueous environments. These compounds are classified under the Biopharmaceutical Classification System (BCS) as either class II or class IV substances. Different carriers were used to increase their solubility. Candesartan cilexetil (CC) is one of the most widely used antihypertensive drugs, which belongs to class II drugs. The aim of this research was to enhance the solubility and dissolution rate of CC through a complexation approach involving β-cyclodextrin and its derivatives, specifically hydroxypropyl beta cyclodextrin (HP-β-CD), methyl beta cyclodextrin (M-β-CD), and sulfonyl ether beta-cyclodextrin (SBE-β-CD), serving as complexing agents. This complexation process was investigated both with and without the inclusion of poloxamer 407 (PX407) as a hydrophilic polymer. The complex was prepared through a combination of grinding, kneading, and co-evaporation techniques. The resulting complex underwent characterization, including assessments of its percentage yield, drug content, solubility, and dissolution properties, as well as analyses using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and fourier transforms infrared spectroscopy (FTIR). The results revealed that, the complex prepared using 1:1 molar ratio of M -β-CD:CC in the presence of 5% w/w PX407 by co-evaporation method had the highest percentage yield (97%) with drug content of 98.5%, the highest solubility (0.052 mg/mL) and fastest release of drug within 45 minutes compared to the other methods. The FTIR, DSC, and XRD confirmed the development of a partial inclusion complex of an amorphous nature

Fabrication of Stable Dual‐Layer Polymer‐Based Nanofibers with Applications for Food Preservation

AbstractThe aim of the study was to produce dual nanofibers (NFs) with antibacterial and antioxidant properties, and to determine the potential use of dual NFs in food preservation. For this purpose, Polycaprolactone (PCL) polymers and Hydroxypropyl Beta Cyclodextrin (HPβ‐CD) polymer were used to produce nanofibers. Nisin, which is in the GRAS class, was used for the antibacterial properties of NFs and black seed cumin oil (BCSO) was used for antibacterial and antioxidant effects. PCL_BCSO‐NFs has an antimicrobial effect on both Gram‐positive and Gram‐negative bacteria. Furthermore, PCL_BCSO‐NFs showed antibacterial activity of 50 % and above after long periods of storage at the room temperature. Nisin loaded HPβ‐CD‐NF and dual layer nanofiber exhibited antibacterial activity of 3.5±0.3 cm and 3.1±0.3 cm zone diameter against S. aureus and E. coli respectively. Furthermore, PCL/BCSO‐HPβ_CD/Nisin‐NFs showed a high antimicrobial effect until day 60. Antioxidant activity of PCL_BCSO‐NFs was 63.2 % while 52.9 % was observed by dual layer NFs. In addition, the antioxidant activity of PCL/BCSO‐HPβ_CD/Nisin‐NFs ranged from 52 to 70 % for 1d and 7 days storage period. Therefore, nanofiber based mats containing BCSO and nisin as a food packaging material can potentially provide protection to extend the shelf life of food products.

Hydroxypropyl-Beta Cyclodextrin Barrier Prevents Respiratory Viral Infections: A Preclinical Study.

The emergence and mutation of pathogenic viruses have been occurring at an unprecedented rate in recent decades. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global public health crisis due to extensive viral transmission. In situ RNA mapping has revealed angiotensin-converting enzyme 2 (ACE2) expression to be highest in the nose and lower in the lung, pointing to nasal susceptibility as a predominant route for infection and the cause of subsequent pulmonary effects. By blocking viral attachment and entry at the nasal airway using a cyclodextrin-based formulation, a preventative therapy can be developed to reduce viral infection at the site of entry. Here, we assess the safety and antiviral efficacy of cyclodextrin-based formulations. From these studies, hydroxypropyl beta-cyclodextrin (HPBCD) and hydroxypropyl gamma-cyclodextrin (HPGCD) were then further evaluated for antiviral effects using SARS-CoV-2 pseudotypes. Efficacy findings were confirmed with SARS-CoV-2 Delta variant infection of Calu-3 cells and using a K18-hACE2 murine model. Intranasal pre-treatment with HPBCD-based formulations reduced viral load and inflammatory signaling in the lung. In vitro efficacy studies were further conducted using lentiviruses, murine hepatitis virus (MHV), and influenza A virus subtype H1N1. These findings suggest HPBCD may be used as an agnostic barrier against transmissible pathogens, including but not limited to SARS-CoV-2.

Important role of cosolvent addition and soil permeability on electrokinetic-persulfate remediation of benzo(a)pyrene

Benzo(a)pyrene (BaP) is a common soil pollutant that is difficult to remove from low-permeability soil. The effects of cosolvent and soil permeability on electrokinetic (EK) + persulfate (PS) remediation of BaP are not well understood. This study investigated BaP removal in two soil types of different low permeabilities (low: Soil-L; much lower: Soil-ML) under different types and concentrations of cosolvent-enhanced EK+PS remediation. In Soil-ML, BaP removal varied significantly, reaching up to 86.6% under EK+PS+ 5% hydroxypropyl-beta-cyclodextrin (HPCD) treatment. Compared to EK+PS alone, the promoting effect of HPCD on EK+PS increased with increased concentrations of HPCD; however, adding 1% Tween 80 (TW 80) suppressed BaP removal by 2.5–10.5% in the soil compared with that under EK+PS alone. The inhibition was further enhanced at 10% TW 80, with an average BaP removal of 36.2%. In contrast, in Soil-L, BaP removal was higher than in Soil-ML under EK+PS alone (additional 4.4–22.5%). Adding HPCD slightly inhibited BaP removal and adding 1% TW 80 had a slightly positive effect. PS migration (measured S2O82-) was impeded because of the low electroosmotic flow generated in Soil-ML, with higher clay, silt, and bound water contents. Overall, this study provides valuable insights into the EK remediation of polycyclic aromatic hydrocarbons in low-permeability soils.

Preparation, characterization, and pharmacokinetics study of apocynin and vanillic acid via hydroxypropyl-beta-cyclodextrin encapsulation

Apocynin (AP) and vanillic acid (VA) are rich antioxidant has a broad spectrum of pharmacological activities. However, its practical administration has been limited due to poor aqueous solubility and bioavailability. Hence Cyclodextrins are used to improve the solubility and oral bioavailability of AP and VA via Hydroxypropyl beta-cyclodextrin (HPBCD) formulation. HPBCD inclusion complex with AP-VA was synthesized and characterized for its physicochemical properties. The average particle size of HPBCD-AP-VA was 164.1 ± 1.3nm, 146.7 ± 2.0nm, and zeta potential was -30.0 mv and -17.3 mv. The encapsulation `efficiency was found to be 97% and 95%, respectively. AFM, SEM, and TEM confirmed the size, spherical nature, and smooth surface of the inclusion complex. The results of XRD, DSC and FTIR, indicated that AP-VA successfully entered the cavity of HPBCD. In vitro bioaccessibility result revealed that HPBCD inclusions were more accessible when compared to Native form. Further, in vivo bioavailability study showed high concentration of HPBCD-AP-VA complex in plasma (25mg/kg bwt) and compared to Native. The Tmax and AUC of HPBCD complex in plasma was 2h and 253.46 ± 3.42, 249.28 ± 2.31 respectively. The results of the study revealed that using HPBCD to encapsulate AP-VA can be beneficial for the pharmacological uses.

Formulation, Optimization and Evaluation of Nutraceutical Effervescent Granules Containing Curcumin and Ascorbic Acid by Fusion Technique Using Full Factorial Design

Recent studies suggest that curcumin has potent immunological activity in combination with ascorbic acid. Hence, research was carried out to formulate effervescent granules of curcumin and ascorbic acid as preventive measures for COVID-19. Thirteen formulas (F1 to F13) were prepared by applying 32 full factorial designs by applying the fusion method using Stat-Ease Design-Expert v7.0.0 software. Here, a complex of hydroxypropyl beta-cyclodextrin and curcumin was prepared by lyophilization technique to improve the solubility of curcumin. Citric acid, tartaric acid, sodium bicarbonate, polyethylene glycol, and sorbitol were used in the formulation of effervescent granules. Evaluation studies were carried out for all 13 formulas, including compatibility study, flowability study and effervescence time. The results show that granules have excellent flow property with an appropriate bulk density and tapped density for the uniting dose. The FTIR study also indicates that there is no interaction between excipients. The effervescence time is less than 3 minutes for all the batches. Formula 4 shows the best effervescence. This research article covers the development of effervescent granules containing curcumin, which has antiviral properties (both through direct movement on viruses and through modulating the immune system). With the pandemic of coronavirus that we are facing, curcumin and ascorbic acid can provide us protection against COVID-19 by keeping our immunity up and protecting against the onslaught of infections.

Development and In-Vitro characterization of risperidone loaded hydroxy propyl beta cyclodextrin nanosponge for enhancing bioavailability

The purpose of the study was to develop and evaluate risperidone loaded nanosponge having prolonged residence time and sustained drug release. Nanosponges were prepared by emulsification solvent evaporation technique using cyclodextrins polymers in varying ratios. The nanosponges were evaluated for its percentage yield, drug entrapment efficiency, particle size and shape and In vitro drug release studies. The FTIR studies revealed uniform caging of the drug into the beta cyclodextrin cavity. The cyclodextrin based nanosponge showed particle size, drug entrapment efficiency and yield in the ranges of 148 - 164μm, 68.0 - 85.0% and 67.52 - 87.25% respectively. In vitro drug release confirms that formulation F2 was the best formulation as it was discovered that the nanosponge formulation's % release was 98.17±0.31% for 60 mins. This confirms the developed nanosponges are promising and have better bioavailability.

Enhancement of apixaban's solubility and dissolution rate by inclusion complex (β-cyclodextrin and hydroxypropyl β-cyclodextrin) and computational calculation of their inclusion complexes.

Apixaban (AP) is a factor X inhibitor, an orally active drug that inhibits blood coagulation for better prevention of venous thromboembolism. It has poor solubility, dissolution rate and low bioavailability. The aim of this study was to improve the aqueous solubility and dissolution rate of oral AP as a step to enhance its bioavailability by preparing it as an inclusion complex with beta- and hydroxy propyl beta-cyclodextrin. A simple, rapid method of analysis of AP was developed using ultraviolet spectrophotometry (UV) and partially validated in terms of linearity, precision and accuracy, recovery, and robustness. AP was prepared as a complex with beta cyclodextrin (βCD) and hydroxy propyl beta cyclodextrin (HPβCD) in weight ratios 1:1, 1:2, and 1:3 by kneading, solvent evaporation and spray drying methods and characterized by Fourier transfer infra-red (FTIR), differential scanning calorimetry (DSC), and percent drug content in each of the prepared complex. Using the computer simulation, the interactions of AP with βCD and HPβCD were investigated. The phase solubility study showed that the solubility of AP was greatly enhanced from 54×10-3 mmol /L to 66 mmol/L using HPβCD with acceptable stability constant. Computer docking supports the formation of a stable 1:1 complex between AP and CD's. The dissolution test results showed that the complex gave a significantly higher percentage of drug release (95%) over one hour compared to the free AP (60%) (p<0.05). AP- HPβCD complex in the ratio of 1:2 (w/w) can significantly improve the solubility and in vitro dissolution rate of AP.

Orally fast-dissolving drug delivery systems for pediatrics: Nanofibrous oral strips from isoniazid/cyclodextrin inclusion complexes

Isoniazid (INH) is an essential antibiotic for tuberculosis that suffers from low water-solubility and limited bioavailability due to its crystalline form. Generation of inclusion complex nanofibrous film of isoniazid with highly water soluble cyclodextrin derivates can enable to develop a new oral delivery system with fast-disintegrating feature. In this study, the inclusion complex (IC) of INH and hydroxypropyl-beta cyclodextrin (HPβCyD) were fabricated into nanofibrous film through electrospinning technique. Here, HPβCyD was used for both encapsulation of INH and electrospinning of free-standing nanofibrous films. Electrospinning of INH/HPβCyD-IC system resulted into uniform and homogenous fiber morphology having ∼400 nm mean diameter. The ultimate INH/HPβCyD-IC nanofibers were obtained with a ∼100% of loading efficiency (∼8% (w/w) of INH content) without loss of drug content during whole process. Due to inclusion complexation, the electrospinning and so the amorphization of INH within the INH/HPβCyD-IC nanofibrous film was achieved without the use of any organic solvents or toxic agents. The amorphous state of INH and the unique properties of nanofibrous matrix ensured faster and enhanced release profile for INH molecules compared to its pristine powder form. Additionally, INH/HPβCyD-IC nanofibrous film presented a quite fast-disintegration profile in the saliva simulation (∼2s). Overall, this approach revealed a promising administration way as orally fast-dissolving drug delivery system especially for pediatric patients.

Screening of Cyclodextrins in the Processing of Buserelin Dry Powders for Inhalation Prepared by Spray Freeze-Drying.

In this study, we prepared inhalable buserelin microparticles using the spray freeze-drying (SFD) method for pulmonary drug delivery. Raffinose as a cryoprotectant carrier was combined with two levels of five different cyclodextrins (CDs) and then processed by SFD. Dry powder diameters were evaluated by laser light scattering and morphology was determined by scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis were utilized for the determination of crystalline structures. The aerodynamic properties of the spray freeze-dried powders were evaluated by twin stage impinger (TSI) and the stability of prepared samples was assessed under normal and accelerated conditions. The prepared powders were mostly porous spheres and the size of microparticles ranged from 9.08 to 13.53 μm, which are suitable as spray-freeze dried particles. All formulations showed amorphous structure confirmed by DSC and XRD. The aerosolization performance of the formulation containing buserelin, raffinose and 5% beta-cyclodextrin (β-CD), was the highest and its fine particle fraction (FPF) was 69.38%. The more circular and separated structures were observed in higher concentrations of CDs, which were compatible with FPFs. The highest stability was obtained in the formulation containing hydroxypropyl beta-cyclodextrin (HP-β-16. CD) 5%. On the contrary, sulfobutylether beta-cyclodextrin (SBE-β-CD) 5% bearing particles showed the least stability. By adjusting the type and ratio of CDs in the presence of raffinose, the prepared formulations could effectively enhance the aerosolization and stability of buserelin. Therefore, they can be proposed as a suitable career for lung drug delivery.

Hydroxypropyl-beta-Cyclodextrin embedded resveratrol regulates gut microbiota to prevent NAFLD via activating AMPK signaling pathway

Non-alcoholic fatty liver disease (NAFLD) has become a globally rising issue that can cause liver-related morbidity and mortality. Recent studies have revealed that a high-fat diet (HFD) highly contributes to the prevalence and progression of NAFLD via impacting gut microbiota and lipid metabolism signal pathways. Resveratrol (RSV), a natural bioactive compound, has exhibited potential for preventing and alleviating NAFLD. However, due to the poor bioavailability of RSV, its strengths and underlying mechanisms for NAFLD therapeutic potential are poorly understood. To address this, we utilized Hydroxypropyl-beta-Cyclodextrin (HBC) to encapsulate RSV to enhance its water solubility and conducted prevention and intervention experiments in HFD-fed mice. The results showed that the HBC has significantly enhanced the water solubility of RSV by 250-fold and the HBC-RSV better prevented and alleviated the liver steatosis, obesity and abnormal lipid metabolism induced by HFD than RSV alone. Meanwhile, combining HFD and HBC-RSV or RSV prevented HFD mice progressing to NAFLD. Besides, further investigation indicated that RSV could resist liver injury and obesity by modulating gut microbiota, raising the levels of short-chain fatty acids (SCFAs) and activating AMP-activated protein kinase (AMPK) signaling pathway. The activated pathway down-regulated sterol receptor element binding protein 1c (SREBP1c) and acetyl-coenzyme A carboxylase (ACC) to decrease lipid synthesis and up-regulated peroxisome proliferators-activated receptorα (PPARα) to promote the fatty acid oxidation, thus preventing NAFLD. Our findings suggested that water solubility-enhanced RSV beneficially modulated gut microbiota, altered gut microbiota-derived SCFAs, and activated lipid metabolism regulatory pathways, providing potential for NAFLD prevention and alleviation.

Co-encapsulation of curcumin and quercetin with zein/HP-β-CD conjugates to enhance environmental resistance and antioxidant activity

In this study, composite nanoparticles consisting of zein and hydroxypropyl beta-cyclodextrin were prepared using a combined antisolvent co-precipitation/electrostatic interaction method. The effects of calcium ion concentration on the stability of the composite nanoparticles containing both curcumin and quercetin were investigated. Moreover, the stability and bioactivity of the quercetin and curcumin were characterized before and after encapsulation. Fluorescence spectroscopy, Fourier Transform infrared spectroscopy, and X-ray diffraction analyses indicated that electrostatic interactions, hydrogen bonding, and hydrophobic interactions were the main driving forces for the formation of the composite nanoparticles. The addition of calcium ions promoted crosslinking of the proteins and affected the stability of the protein–cyclodextrin composite particles through electrostatic screening and binding effects. The addition of calcium ions to the composite particles improved the encapsulation efficiency, antioxidant activity, and stability of the curcumin and quercetin. However, there was an optimum calcium ion concentration (2.0 mM) that provided the best encapsulation and protective effects on the nutraceuticals. The calcium crosslinked composite particles were shown to maintain good stability under different pH and simulated gastrointestinal digestion conditions. These results suggest that zein–cyclodextrin composite nanoparticles may be useful plant-based colloidal delivery systems for hydrophobic bio-active agents.

Enhanced Solubility and Stability of Aripiprazole in Binary and Ternary Inclusion Complexes Using Hydroxy Propyl Beta Cyclodextrin (HPβCD) and L-Arginine.

The low water solubility of an active pharmaceutical ingredient (aripiprazole) is one of the most critical challenges in pharmaceutical research and development. This antipsychotic drug has an inadequate therapeutic impact because of its minimal and idiosyncratic oral bioavailability to treat schizophrenia. The main objective of this study was to improve the solubility and stability of the antipsychotic drug aripiprazole (ARP) via forming binary as well as ternary inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD) and L-Arginine (LA) as solubility enhancers. Physical mixing and lyophilization were used in different molar ratios. The developed formulations were analyzed by saturation solubility analysis, and dissolution studies were performed using the pedal method. The formulations were characterized by FTIR, XRD, DSC, SEM, and TGA. The results showcased that the addition of HPβCD and LA inclusion complexes enhanced the stability, in contrast to the binary formulations and ternary formulations prepared by physical mixing and solvent evaporation. Ternary formulation HLY47 improved dissolution rates by six times in simulated gastric fluid (SGF). However, the effect of LA on the solubility enhancement was concentration-dependent and showed optimal enhancement at the ratio of 1:1:0.27. FTIR spectra showed the bond shifting, which confirmed the formation of new complexes. The surface morphology of complexes in SEM studies showed the rough surface of lyophilization and solvent evaporation products, while physical mixing revealed a comparatively crystalline surface. The exothermic peaks in DSC diffractograms showed diminished peaks previously observed in the diffractogram of pure drug and LA. Lyophilized ternary complexes displayed significantly enhanced thermal stability, as observed from the thermograms of TGA. In conclusion, it was observed that the preparation method and a specific drug-to-polymer and amino acid ratio are critical for achieving high drug solubility and stability. These complexes seem to be promising candidates for novel drug delivery systems development.

Solid lipid nanoparticles cyclodextrin-decorated incorporated into gellan gum-based dry floating in situ delivery systems for controlled release of bioactive compounds of safflower (Carthamus tinctorius. L): A proof of concept study in biorelevant media

Safflower (Carthamus tinctorius L.) has been explored as a source of natural antioxidant. However, quercetin 7-O-beta-D-glucopyranoside and luteolin 7-O-beta-D-glucopyranoside, as its bioactive compounds, possessed poor aqueous solubility, limiting its efficacy. Here, we developed solid lipid nanoparticles (SLNs) decorated with hydroxypropyl beta-cyclodextrin (HPβCD) incorporated into dry floating gel in situ systems to control the release of both compounds. Using Geleol® as a lipid matrix, SLNs were <200 nm in size with >80 % of encapsulation efficiency. Importantly, following the decoration using HPβCD, the stability of SLNs in gastric environment was significantly improved. Furthermore, the solubility of both compounds was also enhanced. The incorporation of SLNs into gellan gum-based floating gel in situ provided desired flow and floating properties, with <30 s gelation time. The floating gel in situ system could control the release of bioactive compounds in FaSSGF (Fasted-State Simulated Gastric Fluid). Furthermore, to assess the effect of food intake on release behavior, we found that the formulation could show a sustained release pattern in FeSSGF (Fed-State Simulated Gastric Fluid) for 24 h after being released in FaSGGF for 2 h. This indicated that this combination approach could be a promising oral delivery for bioactive compounds in safflower.

A Promising Ternary Solid Dispersion of Aceclofenac Containing Tablet with Enhanced Dissolution, and Potentiated Anti-inflammatory Efficacy

The major objective of the current study is to implement a plan to enhance the dissolution rate and oral bioavailability of a poorly water-soluble aceclofenac. The drug is classified according to the biopharmaceutical classification system as class II drug. Amorphous alkalinized aceclofenac solid dispersion was formulated as a ternary mixture. This mixture was prepared by introducing polymeric carriers [polyvinylpyrrolidone, Hydroxy propyl beta cyclodextrin or Polyethylene glycol] and an alkalizer (Na2CO3) by applying the solvent evaporation method. Optimum formulations were compressed into tablets that were subjected to in-vitro studies compared to the market product Bristaflam and free drug containing one. Finally, tablets were assessed for stability studies and carrageenan-induced rat paw edema treatment to evaluate potentiated anti-inflammatory efficacy.&#x0D; Results showed that optimum amorphous alkalinized aceclofenac solid dispersion formulations containing polyvinylpyrrolidone K30 or Hydroxy propyl beta cyclodextrin in 1:5 ratio have significant in-vitro dissolution improvement (&gt;90% in 10 min) compared to untreated aceclofenac. Solid-state characterization emphasized the conversion of the crystalline drug into the amorphous form with no drug−polymers interactions. Stability and dissolution studies ensured that tablets containing amorphous alkalinized solid dispersions were stable with strikingly improving dissolution behavior compared to Bristaflam or free drug containing tablets. Moreover, regarding anti-inflammatory activity against carrageenan induced paw edema, and histopathological examination, we concluded that amorphous alkalinized solid dispersions containing tablets are a promising approach to enhance the dissolution rate and oral bioavailability and hence anti-inflammatory efficacy of aceclofenac.

Rutin Nanocrystals with Enhanced Anti-Inflammatory Activity: Preparation and Ex Vivo/In Vivo Evaluation in an Inflammatory Rat Model.

Rutin is a polyphenolic flavonoid with an interestingly wide therapeutic spectrum. However, its clinical benefits are limited by its poor aqueous solubility and low bioavailability. In an attempt to overcome these limitations, rutin nanocrystals were prepared using various stabilizers including nonionic surfactants and nonionic polymers. The nanocrystals were evaluated for particle size, zeta potential, drug entrapment efficiency, morphology, colloidal stability, rutin photostability, dissolution rate, and saturation solubility. The selected nanocrystal formulation was dispersed in a hydrogel base and the drug release kinetics and permeability through mouse skin were characterized. Rutin's anti-inflammatory efficacy was studied in a carrageenan-induced rat paw edema model. The nanocrystals had a size in the range of around 270-500 nm and a polydispersity index of around 0.3-0.5. Nanocrystals stabilized by hydroxypropyl beta-cyclodextrin (HP-β-CD) had the smallest particle size, highest drug entrapment efficiency, best colloidal stability, and highest drug photostability. Nanocrystals had around a 102- to 202-fold and 2.3- to 6.7-fold increase in the drug aqueous solubility and dissolution rate, respectively, depending on the type of stabilizer. HP-β-CD nanocrystals hydrogel had a significantly higher percent of drug released and permeated through the mouse skin compared with the free drug hydrogel. The cumulative drug amount permeated through the skin was 2.5-fold higher than that of the free drug hydrogel. In vivo studies showed that HP-β-CD-stabilized rutin nanocrystals hydrogel had significantly higher edema inhibition compared with the free drug hydrogel and commercial diclofenac sodium gel. These results highlight the potential of HP-β-CD-stabilized nanocrystals as a promising approach to enhance drug solubility, dissolution rate, and anti-inflammatory properties.

Formulation and Evaluation of Solid Dispersion of Poorly Soluble Drugs

Solid dispersion is one of the method, which was most widely and successfully applied to improve the solubility, dissolution rates and consequently the bioavailability of poorly soluble drugs. The solid dispersion based on the concept that the drug is dispersed in an inert water- soluble carrier at solid state. Several water-soluble carriers such as methyl cellulose, urea, lactose, citric acid, polyvinyl pyrrolidone and HPMC, cyclodextrin, polyethylene glycols 4000 and 6000 are used as carriers for solid dispersion. In the current research work, the solid dispersion technique can be successfully used for the improvement of dissolution of piperine and sulfamethaoxazole. In this regards, solid dispersions of these drugs were prepared by using HPMC E 100 and 2-Hydroxyproplyl beta cyclodextrin as a carrier in 1:1 ratio by solvent evaporation method. The saturation solubility and in-vitro dissolution studies of prepared solid dispersions were examined against pure piperine and sulfamethaoxazole. Faster dissolution was exhibited by piperine-2 hydroxypropyl beta cyclodextrin solid dispersion containing 1:1 ratio.