Candesartan Research Articles

Effective drug design screening in bacterial glycolytic enzymes via targeting alternative allosteric sites

Three glycolytic enzymes phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GADPH) and pyruvate kinase (PK) that belong to Staphylococcus aureus were used as targets for screening a dataset composed of 7229 compounds of which 1416 were FDA-approved. Instead of catalytic sites, evolutionarily less conserved allosteric sites were targeted to identify compounds that would selectively bind the bacteria's glycolytic enzymes instead of the human host. Seven different allosteric sites provided by three enzymes were used in independent screening experiments via docking. For each of the seven sites, a total of 723 compounds were selected as the top 10 % which displayed the highest binding affinities. All compounds were then united to yield the top 54 drug candidates shared by all seven sites. Next, 17 out of 54 were selected and subjected to in vitro experiments for testing their inhibition capability for antibacterial growth and enzymatic activity. Accordingly, four compounds displaying antibacterial growth inhibition above 40 % were determined as Candesartan cilexetil, Montelukast (sodium), Dronedarone (hydrochloride) and Thonzonium (bromide). In a second round of experiment, Candesartan cilexetil and Thonzonium displayed exceptionally high killing efficiencies on two bacterial strains of S.aureus (methicillin-sensitive and methicillin-resistant) with concentrations as low as 4 μg/mL and 0.5 μg/mL. Yet, their enzymatic assays were not in accordance with their killing effectiveness. Different inhibitory effects was observed for each compound in each enzymatic assay. A more effective target strategy would be to screen for drug compounds that woud inhibit a combination of glycolytic enzymes observed in the glycolytic pathway.

Phase III randomized clinical trial of efficacy and safety of amlodipine and candesartan cilexetil combination for hypertension treatment

Effective antihypertensive therapy is essential for achieving optimal blood pressure (BP) control and reducing cardiovascular events. This double-blind, multicenter, randomized trial aimed to compare the antihypertensive efficacy and safety of a combination of amlodipine (AML) and candesartan cilexetil (CC) versus AML monotherapy in patients with essential hypertension (HTN). After a 4-week run-in period with AML 5 mg, patients whose HTN remained uncontrolled (diastolic BP [DBP]) ≥ 90 mmHg and < 120 mmHg) were randomized to receive either AML + CC or AML alone for 8 weeks. Efficacy was assessed by measuring changes in DBP and systolic BP (SBP). The primary safety measure was the incidence of adverse events (AEs). A total of 174 participants were included in the efficacy analysis. After 8 weeks, DBP decreased by -9.92 ± 0.86 mmHg in the AML + CC arm and - 2.08 ± 0.86 mmHg in the AML arm (p < 0.0001). SBP decreased by -14.27 ± 1.39 mmHg in the AML + CC arm versus - 2.77 ± 1.39 mmHg in the AML arm (p < 0.0001). AEs occurred in 11.24% of the AML + CC group and 5.62% of the AML group (p = 0.1773). AML + CC combination therapy demonstrated superior efficacy with good tolerance, making it a promising option for patients with inadequately controlled hypertension on amlodipine alone.

Accurate determination of three new antihypertensive drugs illegally added to food using ultra-high performance liquid chromatography-tandem mass spectrometry

Effective strategies are required to address food safety issues related to the illegal addition of antihypertensive drugs to food and claims of antihypertensive function. In this study, a novel ultra-high performance liquid chromatography-triple-quadrupole mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of three antihypertensive drugs (azilsartan, candesartan cilexetil, and lacidipine) in 12 food matrices (pressed candies, solid beverages, alternative teas, tea drinks, biscuits, jellies, mixed liquors, oral liquids, medicinal teas, tablets, hard capsules, and soft capsules). Initially, mass spectrometry parameters, such as the collision energies of the three antihypertensive drugs, were optimized. Subsequently, the response intensities and chromatographic separation conditions of the three drugs in different mobile phases were compared. In addition, to enhance the recoveries, various extraction solvents and purification methods, including solid-phase extraction (SPE) columns and the QuEChERS technique, were investigated. In the developed method, sample determination involved three steps. First, the sample was extracted using 0.2% (v/v) formic acid in acetonitrile and then filtered using high-speed centrifugation, in addition, the extracted solution of alternative tea and medicinal tea was purified using the QuEChERS technique. Second, the supernatant was diluted with water, and filtered through a 0.22 μm polytetrafluoroethylene (PTFE) membrane. Finally, the analytes were separated on an Agilent Eclipse Plus RRHD C18 column (50 mm×2.1 mm, 1.8 μm) using a 5 mmol/L ammonium formate aqueous solution and acetonitrile as the mobile phases under gradient elution conditions and then detected using UHPLC-MS/MS with positive electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Quantitative analysis was performed using a matrix-matched external standard method. Methodological validation showed good linear relationships for all three antihypertensive drugs in the investigated concentration ranges, with correlation coefficients (r2) greater than 0.996. The limit of detection (LOD) and limit of quantification (LOQ) of lacidipine were 0.02 mg/kg and 0.04 mg/kg, respectively, whereas those of the other two drugs were 0.01 mg/kg and 0.02 mg/kg, respectively. In the 12 food matrices, the average recoveries of the drugs ranged from 86.6% to 107.5% with relative standard deviations (RSDs) of 1.1%-10.9% (n=6) at low, medium, and high spiked levels. Furthermore, this method was successfully applied to the analysis of real food samples. Overall, the newly developed method is simple, rapid, sensitive, accurate, and suitable for the qualitative and quantitative determination of antihypertensive drugs in different food matrices. This work could provide technical support for food safety agencies in implementing measures against the illegal addition of antihypertensive drugs to food.

In Vitro and in vivo characterization of nasal pH-Responsive in-situ hydrogel of Candesartan-loaded invasomes as a potential stroke treatment.

Candesartan (CDN) is a useful anti-stroke medication because it lowers blood pressure, inflammation, oxidative stress, angiogenesis and apoptosis. However, CDN has limited efficacy due to its low solubility and poor bioavailability. This study set out to develop nasal pH-responsive in situ hydrogel of CDN-loaded invasomes a (PRHCLI) for enhancing CDN's release, penetration, bioavailability, and effectiveness as a possible treatment for stroke. Based on the results of the pre-formulation investigation, the optimum CLI formulation for intravasomal delivery of CDN was determined to be 3% of phospholipid, 0.16% of cholesterol, 3% of ethanol, and 1% of cineole. The optimum formulation significantly enhanced CDN permeation and release by 2.06-fold and 59.06%, respectively. The CLI formulation was added to a mixture of chitosan (0.67%w/v) and glyceryl monooleate (0.27%v/v) to develop PRHCLI. The PRHCLI formulation enhanced the release and permeation of CDN relative to free CDN by 2.15 and 2.76 folds, respectively. An experimental rat stroke model was utilized for in vivo studies to evaluate the bioavailability, effectiveness, and toxicity of the PRHCLI formulation. The nasal PRHCLI drops increased the CDN's bioavailability by 3.20-fold compared to oral free CDN. Increased grip strength and decreased flexion, spontaneous motor activity, and Morris Water Maze scores in comparison to oral free CDN showed that nasal PRHCLI drops have better anti-stroke activity. The toxicity evaluation revealed the safety of nasal PRHCLI. Hence, nasal PRHCLI drops may represent a promising avenue as a stroke therapy.

Candesartan restores blood-brain barrier dysfunction, mitigates aberrant gene expression, and extends lifespan in a knockin mouse model of epileptogenesis.

Blockade of Angiotensin type 1 receptor (AT1R) has potential therapeutic utility in the treatment of numerous detrimental consequences of epileptogenesis, including oxidative stress, neuroinflammation, and blood-brain barrier (BBB) dysfunction. We have recently shown that many of these pathological processes play a critical role in seizure onset and propagation in the Scn8a-N1768D mouse model. Here we investigate the efficacy and potential mechanism(s) of action of candesartan (CND), an FDA-approved angiotensin receptor blocker (ARB) indicated for hypertension, in improving outcomes in this model of pediatric epilepsy. We compared length of lifespan, seizure frequency, and BBB permeability in juvenile (D/D) and adult (D/+) mice treated with CND at times after seizure onset. We performed RNAseq on hippocampal tissue to quantify differences in genome-wide patterns of transcript abundance and inferred beneficial and detrimental effects of canonical pathways identified by enrichment methods in untreated and treated mice. Our results demonstrate that treatment with CND gives rise to increased survival, longer periods of seizure freedom, and diminished BBB permeability. CND treatment also partially reversed or 'normalized' disease-induced genome-wide gene expression profiles associated with inhibition of NF-κB, TNFα, IL-6, and TGF-β signaling in juvenile and adult mice. Pathway analyses reveal that efficacy of CND is due to its known dual mechanism of action as both an AT1R antagonist and a PPARγ agonist. The robust effectiveness of CND across ages, sexes and mouse strains is a positive indication for its translation to humans and its suitability of use for clinical trials in children with SCN8A epilepsy.

Integrating Quality by Design Principles for Elevating Bioavailability of Candesartan Cilexetil in Fast-dissolving Tablets

Integrating Quality by Design Principles for Elevating Bioavailability of Candesartan Cilexetil in Fast-dissolving Tablets

Integrating Quality by Design Principles for Elevating Bioavailability of Candesartan Cilexetil in Fast-dissolving Tablets

Integrating Quality by Design Principles for Elevating Bioavailability of Candesartan Cilexetil in Fast-dissolving Tablets

Candesartan Cilexetil Formulations in Mesoporous Silica: Preparation, Enhanced Dissolution In Vitro, and Oral Bioavailability In Vivo

Candesartan cilexetil (CC) is one of well-tolerated antihypertensive drugs, while its poor solubility and low bioavailability limit its use. Herein, two mesoporous silica (Syloid XDP 3150 and Syloid AL-1 FP) and the corresponding amino-modified products (N-XDP 3150 and N-AL-1 FP) have been selected as the carriers of Candesartan cilexetil to prepare solid dispersion through solvent immersion, and characterized through using powder X-ray diffraction analysis, infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, and solid-state nuclear magnetic resonance spectroscopy, etc. The state of CC changed from crystalline to amorphous after loading onto the silica carriers, in which no interactions between CC and silica existed. Then, the dissolution behaviors in vitro were studied through using flow-through cell dissolution method. CC-XDP 3150 sample exhibited the most extensive dissolution, and the cumulative release of CC from it was 1.88-fold larger than that of CC. Moreover, the pharmacokinetic results in rats revealed that the relative bioavailability of CC-XDP 3150 and CC-N-XDP 3150 solid dispersions were estimated to be 326 % % and 238 % % in comparison with CC, respectively. Clearly, pore size, pore volume, and surface properties of silica carrier have remarkable effect on loading, dissolution and bioavailability of CC. In brief, this work will provide valuable information in construction of mesoporous silica-based delivery system toward poorly water-soluble drugs.

Unraveling the molecular regulation of biofilm underlying effect of chronic disease medications.

A biofilm is a complex microbial structure that promotes the progression of persistent infections, particularly in nosocomial settings via indwelling medical devices. Conventional antibiotics are often ineffective treatments for biofilms; hence, it is crucial to investigate or design non-antibiotic antibiofilm compounds that can successfully reduce and eradicate biofilm-related infections. This study was an attempt to repurpose chronic disease medications of the antihypertensive and antilipidemic drug classes, including candesartan cilexetil (CC) and ursodeoxycholic acid (UDCA), respectively, to be used as antibiofilm agents against the two infectious pathogens Staphylococcus aureus and Enterococcus faecalis. Crystal violet (CV) staining assay was used to evaluate the antibiofilm activity of the drugs. Real-time polymerase chain reaction (RT-PCR) was performed to determine the transcription levels of the biofilm-related genes (icaA and icaR in S. aureus and fsrC and gelE in E. faecalis) following treatment with different concentrations of CC and UDCA. we found that a concentration of greater than 1.5 µg/ml of CC significantly (p < 0.005) inhibited the biofilm formation of both bacterial isolates, and a concentration of greater than 50 µg/ml of UDCA significantly (p < 0.005) inhibited the biofilm formation of both bacterial isolates. Interestingly, the mRNA expression levels of biofilm-related genes were decreased in the two bacterial isolates at concentrations that were lower than the human pharmaceutical daily doses.

THE SIMULTANEOUS SPECTRAL DETERMINATION OF CANDESARTAN CILEXETIL AND HYDROCHLOROTHIAZIDE IN TABLETS USING THE TRIVARIATE CLASSICAL LEAST SQUARES METHOD

Objective: Candesartan cilexetil (CDS) is a member of the sartan group of drugs and is widely used to lower blood pressure. Hydrochlorothiazide (HCT) is the most commonly used diuretic group of drugs and is prescribed together with candesartan cilexetil in cases where blood pressure cannot be reduced. Pharmaceutical preparations containing these two active compounds in combination are preferred today to provide a more effective pharmacological effect. Therefore, it is of great importance to determine the quantities of these combined pharmaceutical preparations with new analytical methods that are fast, easy, and sensitive in quality control and routine analysis. In this study, a new trivariate classical least squares calibration method (TCLS) was developed for the simultaneous quantification of candesartan cilexetil (CDS) and hydrochlorothiazide (HCT) in binary mixtures and commercial tablets without using a preliminary separation step. Material and Method: CDS and HCT compounds were kindly donated by National Pharm Ind., Turkey. HPLC-grade methanol (J.T. Baker, Netherlands) was used as a solvent for the spectrophotometric analysis. In the application of the TCLS method, the determination and quantification of CDS and HCT were carried out using UV spectrophotometric measurements with 1 cm quartz cells in the 200-310 nm spectral region (slit range 2 nm). The newly developed TCLS method was tested using a validation set consisting of eight synthetic mixture solutions within the working ranges of 4.0-20.0 μg/ml for CDS and HCT. Simultaneous quantification analyses of CDS and HCT were performed on ATACAND PLUS® Tablet supplied by Astra Zeneca İlaç Ltd Şti. Result and Discussion: The method is based on the application of TCLS to the absorbance measurements at three different wavelength points (223.5, 240.0, and 268.5 nm). The absorptivity values (µg-1mlcm-1) of pure CDS and pure HCT were 6.67x10-2, 2.76x10-2, 2.33x10-2, and 11.41x10-2, 0.46x10-2, 6.42x10-2 at the selected wavelengths, respectively. Recovery values and relative standard deviation values were calculated as 97.2% and 1.61% for CDS and 99.7% and 3.67% for HCT, respectively. This method was successfully applied to the spectrophotometric quantitative analysis of tablets containing CDS and HCT, and then, a good agreement was reported.

Solid dispersion systems for enhanced dissolution of poorly water-soluble candesartan cilexetil: In vitro evaluation and simulated pharmacokinetics studies

Solid dispersion systems for enhanced dissolution of poorly water-soluble candesartan cilexetil: In vitro evaluation and simulated pharmacokinetics studies

Pharmacokinetics and bioequivalence study of candesartan cilexetil tablet in Chinese volunteers under fasting condition: an open-label, randomized-sequence, 2-period crossover study.

Candesartan is an antihypertensive agent that acts on an angiotensin II receptor. Candesartan cilexetil is a prodrug that is converted into the active form of candesartan during intestinal absorption. This study aimed to assess the pharmacokinetics and bioequivalence of a reference and a test formulation of candesartan cilexetil tablets in healthy Chinese volunteers. A randomized, open-label, single-dose, crossover study was conducted with two treatment periods. Forty-eight healthy Chinese volunteers participated under fasted conditions. Qualified subjects were randomly divided into two groups (1:1 ratio) to receive either the test or reference formulation first. A washout period of 14 days separated the administration of the two formulations. Blood samples were collected at specific time points and analyzed for candesartan concentration using Ultra High-Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). The maximum concentration (Cmax), the AUC from time zero to the last measured time point (AUC0-t) and the AUC from time zero to infinity (AUC0-∞) fell within the bioequivalence range of 80% to 125%. These results suggest that the test and reference formulations of candesartan cilexetil tablets are bioequivalent, meaning they have similar rates and extents of absorption in healthy Chinese volunteers. No serious adverse events or side effects were reported throughout the study.

Enhancing simultaneous determination of some angiotensin II receptor antagonists and amlodipine in plasma using HPTLC with fluorescence densitometry: Independent fluorescence detection of the co-administrative drugs in the mixture across various pH conditions

A novel and highly sensitive high-performance thin-layer chromatographic (HPTLC) method was developed and validated to quantify a combination of five pharmaceutical mixtures spiked to human plasma. The compounds comprised Amlodipine (AML) along with five angiotensin II receptor antagonist drugs (AIIRAs), namely Olmesartan (OLM), Telmisartan (TLM), Candesartan (CAN), Losartan (LOS), and Irbesartan (IRB). HPTLC was performed on silica gel 60 F254 plates using a mobile phase of Toluene: ethyl acetate: methanol: acetone: acetic acid (6:1.5:1:0.5:1, v/v/v/v/v). In a pioneering move, a reflectance/fluorescence detection mode was employed to identify two concurrently administered drugs at different pH levels for the first time. This method utilized the same chromatographic system, incorporating a specific measurement for AML at a neutral medium to achieve its maximum fluorescence at a 360 nm excitation wavelength, and measuring emission using a 540 nm optical filter. The process involved obtaining a very low fluorescence response from AIIRA. Subsequently, to enhance AIIRA’s fluorescence, the plate was sprayed with perchloric acid to transition to a strong acidic medium, ultimately attaining the maximum fluorescence of AIIRA using various excitation wavelengths and a 400 nm emission filter. Through this strategic process, we could optimize the fluorescence signals of both drugs, thereby elevating the sensitivity of detection for this drug combination. AML demonstrated a linear range of 18–300 ng/band, while AIIRAs drugs exhibited a linear range of 6–150 ng/band. The method satisfied the International Conference on Harmonization (ICH) criteria for recovery, precision, repeatability, and robustness, showcasing exceptional sensitivity. The approach was successfully applied to quantify AML and AIIRAs drugs in both bulk drug and plasma samples, achieving high recovery percentages and minimal standard deviations.

Pharmacokinetic Comparison of a Fixed-Dose Combination of Candesartan Cilexetil/Amlodipine/Atorvastatin Versus Co-administration of Individual Formulations in Healthy Participants.

Fixed-dose combinations (FDCs) of angiotensinII receptor blockers, calcium channel blockers, and statins are conventional therapeutic interventions prescribed for cardiovascular diseases. This study aimed at drawing a comparison between the pharmacokinetics and safety of an FDC and the corresponding individual formulations in healthy subjects. A randomized, open-label, single-dose, three-sequence, three-period, partially repeated crossover study was conducted with a cohort of healthy volunteers. A 14-day washout period was maintained between each of the three periods. In this study, candesartan cilexetil, amlodipine, and atorvastatin was administered orally as FDCs of 16/10/40mg in study1 and 16/5/20mg in study2. The maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of candesartan, amlodipine, and atorvastatin were estimated as the geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the FDC to individual formulations. If the within-subject coefficient of variation (CVwr) of Cmax was greater than 0.3, the bioequivalence (BE) range calculated using the reference-scaled average bioequivalence was used to assess whether the 90%CI was within the BE range. The GMRs (90%CIs) for the AUClast for candesartan and amlodipine were 0.9612 (0.9158-1.0089)/0.9965 (0.9550-1.0397) and 1.0033 (0.9800-1.0271)/1.0067 (0.9798-1.0344), and the GMRs (90%CIs) for Cmax were 0.9600 (0.8953-1.0294)/0.9851 (0.9368-1.0359) and 1.0198 (0.9950-1.0453)/1.0003 (0.9694-1.0321) in studies1 and 2, respectively. The extended BE ranges calculated from the CVwr of the Cmax of atorvastatin were 0.7814-1.2797 and 0.7415-1.3485, respectively. The GMRs (90%CIs) for the AUClast of atorvastatin were 1.0532 (1.0082-1.1003)/1.0252 (0.9841-1.0680), and the GMRs (90%CIs) for Cmax were 1.0630 (0.9418-1.1997)/0.9888 (0.8792-1.1120) in studies1 and 2, respectively. The Cmax and AUClast values of candesartan cilexetil/amlodipine/atorvastatin 16/10/40mg and 16/5/20mg, respectively, were within the BE ranges. There were no clinically significant differences in safety between the two formulations. ClinicalTrials.gov identifier, study1: NCT04478097; study2: NCT04627207.

Antibacterial Activity and Mechanism of Candesartan Cilexetil against Enterococcus faecalis.

Enterococcus faecalis infections pose a significant clinical challenge due to their multidrug resistance and propensity for biofilm formation. Exploring alternative treatment options, such as repurposing existing drugs, is crucial in addressing this issue. This study investigates the antibacterial activity of candesartan cilexetil against E. faecalis and elucidates its mechanism of action. Candesartan cilexetil exhibited notable antibacterial activity against both E. faecalis and Enterococcus faecium, with minimum inhibitory concentration (MIC) of ≤25 μM. Time-kill curves demonstrated concentration-dependent bactericidal effects. Candesartan cilexetil could significantly inhibited biofilm formation at the concentration of 1/4× MIC and induced alterations in biofilm structure. Permeability assays revealed compromised bacterial membranes, accompanied by the dissipation of membrane potential in E. faecalis cells after treatment with candesartan cilexetil. Checkerboard analysis showed that bacterial membrane phospholipids phosphatidylglycerol and cardiolipin could neutralize the antibacterial activity of candesartan cilexetil in a dose-dependent manner. Biolayer interferometry (BLI) assay indicated specific interactions between candesartan cilexetil and phosphatidylglycerol or cardiolipin. This study demonstrates the promising antibacterial and antibiofilm activities of candesartan cilexetil against multidrug-resistant E. faecalis. The mechanism of action involves disruption of bacterial membranes, possibly by interacting with membrane phospholipids. These findings underscore the potential utility of candesartan cilexetil as an effective therapeutic agent for combating E. faecalis infections, offering a valuable strategy in the battle against antibiotic-resistant pathogens.

Comparison of the Efficacy and Tolerability of Candesartan Cilexetil between Hypertension patients of Muna and Tolaki Ethnicity

There are differences in the efficacy of a drug between ethnicities. Hypertension Treatment Guidelines of JNC 8 recommend not using angiotensin receptor blockers (ARBs) and ACE inhibitors in the black population for first-line therapy. The Tolaki and Muna ethnicities are two indigenous ethnic groups of the Southeast Sulawesi Province of Indonesia. The very different physical characteristics between these two ethnic groups raise the possibility that there are differences in the body's response to antihypertensive ARBs, including candesartan. The study aimed to compare the efficacy and tolerability of candesartan cilexetil monotherapy for one month in hypertensive patients of the Tolaki and Muna ethnicities. Assessment of therapy efficacy includes the proportion of patients achieving the therapeutic target according to JNC 8 and the reduction of blood pressure. Tolerability is assessed based on side effects and adverse drug reactions (ADR) reported by patients. Patients who met the criteria for this study were those who had recently been diagnosed with essential hypertension or hypertension with type 2 diabetes mellitus, were taking candesartan cilexetil (8 mg orally once a day), and had blood pressure values after one month of treatment. Sixty-eight Tolaki ethnic patients and 51 Muna ethnic patients who met the inclusion criteria were included in this study. The results showed that the decrease in systolic and diastolic blood pressure was greater in the Tolaki than those in the Muna ethnicity. The median value of the systolic decrease was -33 ((-10)–(-60)) mmHg for the Tolaki ethnic group and -10 (0–(-20)) mmHg for the Muna ethnic group. The median value of diastolic decline for the Tolaki and Muna ethnicities was -10 (0–(-37)) mmHg and -5 (5–(-20)) mmHg, respectively. The MAP value of the Tolaki ethnic group is 93.30 (80–110), and that of the Muna ethnic group is 110 (96.69–130). The achievement of the target of reducing blood pressure was also significantly higher for the Tolaki than the Muna ethnicities. Complaints felt by some people in both ethnic groups were dizziness, headaches, and feeling weak. Six people in the Muna ethnic group with diabetes mellitus with type 2 experienced hyperkalemia. There was a significant difference in the efficacy of candesartan for one month between Muna and Tolaki ethnic hypertension patients. There was no difference in tolerability between the two ethnic groups.

A Robust and Reliable UPLC Method for the Simultaneous Quantification of Rosuvastatin Calcium, Glibenclamide, and Candesartan Cilexetil

Metabolic syndrome is an associated condition that occurs together and increases the risk of heart disease and diabetes. These conditions include high blood pressure, high blood sugar, and high body mass index (BMI) in terms of cholesterol and triglyceride levels. Most of the elderly population may administer three drugs to control the above conditions. Therefore, this study aims to develop an analytical assay for the precise analysis of three components and to formulate a Self-Nanoemulsifying Drug-Delivery System (SNEDDS) loaded with three drugs: Rosuvastatin Calcium (RC; antilipidemic), Glibenclamide (GB; antidiabetic), and Candesartan Cilexetil (CC; antihypertensive). A design of the experiment was developed at a level of 32, and the influence of column temperature and flow rate was studied in terms of retention time, peak area, peak asymmetry, and resolution. The assay was subjected to several studies to ensure its validation. Under the optimized conditions—column temperature at 50 °C and flow rate at 0.25 mL/min—the three drugs, RC, GB, and CC, are separated. Their retention times are 0.840, 1.800, and 5.803 min, respectively. The assay was valid in terms of linearity, accuracy, and precision. Moreover, the developed assay shows a good tolerance against any change in the condition. The assay was tested also to separate the drugs in a pharmaceutical formulation as SNEDDs. The assay successfully separates the drug with a good resolution.

Management of Xerostomia and Hyposalivation in Hypertensive Patient's Using Candesartan Cilexetil

Saliva’s disorder and dry mouth (xerostomia) are related to routine medication as antihypertensives. Candrsartan cilexetil is an angiotensin receptor blocker (ARB) hypertension drug that indirectly affects saliva by changing fluid and electrolyte balance. To examine the management of xerostomia and hyposalivation in hypertensive patients due to use of candesartan cilexetil. A 70 year old female patient complained her mouth felt dry since 1 year ago when she was diagnosed with hypertension. The patient consumes candesartan cilexetil once daily, 8 mg. Intra oral showed were edentulous areas on the entire upper and lower jaw with the patient's oral mucosa being dry, saliva thick, sticky and frothy. In this case, saliva’s rate measurement showed a result of 0.16 mL/minute. After intervention using dry mouth gel for two weeks, a saliva rate of 0.38 mL/minute. During the control, patient didn’t complaining dry mouth. This is accordance with the literature, dry mouth gel can improve signs and symptoms of dry mouth and increase the patient's ability to swallow. Patient’s take antihypertensive drugs have manifestations in form of xerostomia. The treatment carried out to improve the condition of patient's oral cavity is providing education on maintaining healthy teeth and mouth as well as using dry mouth gel applied to the entire oral mucosa. In this case, an increase salivary rate from 0.16 mL/minute to 0.38 mL/minute. The concluded, use of dry mouth gel is effective in treating xerostomia and can increase the rate of saliva in the oral cavity

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

Formulation and validation of Candesartan cilexetil-loaded nanosuspension to enhance solubility

The following research aimed to enhance solubility by loading candesartan cilexetil into nanosuspension. Candesartan cilexetil-loaded nanosuspension was prepared with the aid of Design-Expert® software. A technique of solvent evaporation was employed to produce nanosuspensions from hydroxyl propyl methyl cellulose (HPMC E5), polyvinyl pyrrolidone (PVP K-30), and poloxamer (PXM 188). The optimised nanosuspensions’ particle size and polydispersity index (PDI) were 64.65 nm and 0.059, respectively. The entrapment efficacy (EE %) and drug loading (DL %) were 86.75 and 10.17%, respectively. The atomic force microscopy (AFM) revealed spherical and smooth nanoparticles. The Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) revealed pure, crystalline and conjugated drugs inside the nanosuspension. The release study confirmed 90% release within 10 min. No significant changes in particle sizes over three months were found, indicating stable nanoparticles. Saturated solubility of the candesartan cilexetil powder and loaded nanosuspension was 63.3 ± 6 and 344.7 ± 16 µg.ml-1, respectively, revealing more than five times increase in solubility. Candesartan cilexetil-loaded nanosuspensions were successfully prepared using different combinations of PVP K-30, HPMC E-5 and PXM 188 in various concentrations. Solubility was enhanced by loading the payload into nanosuspensions.