Drug Release and Stability Study of Innovated Losartan Potassium and Rosuvastatin Calcium Fixed-dose Combination Tablet.

BACKGROUND: Patient adherence to therapy and compliance is always a challenge for care providers in the management of chronic disorders with multiple medications. OBJECTIVE: Our study focused on formulating concurrently prescribed ARB (Angiotensin Receptor Blocker), i.e., losartan potassium, and a cholesterol-lowering statin derivative, i.e., rosuvastatin calcium, in a fixed-dose combination tablet. METHODS: The drugs were selected based on the presence of synergism and variation in solubility characteristics. Trial batches with fixed concentrations of both active pharmaceutical ingredients (APIs) and varying quantities of different excipients were prepared by dry granulation technique and subjected to different quality control tests for tablets. Batch F5 was selected on the basis of in-process quality control data for the development of a drug release protocol. Experimental conditions were optimized. Based on the sink condition, phosphate buffer (pH 6.8) was selected as the dissolution medium. Simultaneous determination of both APIs in samples collected at predetermined time intervals was carried out using the RP-HPLC technique with acetonitrile, methanol, and water (20:25:55 v/v/v) as mobile phase. RESULTS: Complete dissolution of both APIs in the FDC tablet was achieved in 45 min in 900 mL of the selected medium. The in vitro drug release protocol was validated for accuracy and precision without interference with sample analysis. CONCLUSION: In this study, a validated, accurate, and robust dissolution testing method was developed for the newly formulated FDC tablet.

PLGA and PDMS-based in situ forming implants loaded with rosuvastatin and copper-selenium nanoparticles: a promising dual-effect formulation with augmented antimicrobial and cytotoxic activity in breast cancer cells.

Breast cancer is among the most prevalent tumors worldwide. In this study, in-situ forming implants (ISFIs) containing rosuvastatin calcium were prepared using three types of poly (D, L-lactic-co-glycolic acid) (PLGA), namely, PLGA 50/50 with ester terminal and PLGA 75/25 with ester or acid terminal. Additionally, polydimethylsiloxane (PDMS) was added in concentrations of 0, 10, 20, and 30% w/v to accelerate matrix formation. The prepared ISFIs were characterized for their rheological behaviors, rate of matrix formation, and in-vitro drug release. All the prepared formulations revealed a Newtonian flow with a matrix formation rate between 0.017 and 0.059 mm/min. Generally, increasing the concentration of PDMS increased the matrix formation rate. The prepared implants' release efficiency values ranged between 46.39 and 89.75%. The ISFI containing PLGA 50/50 with 30% PDMS was selected for further testing, as it has the highest matrix formation rate and a promising release efficiency value. Copper-selenium nanoparticles were prepared with two different particle sizes (560 and 383 nm for CS1 and CS2, respectively) and loaded into the selected formulation to enhance its anticancer activity. The unloaded and loaded implants with rosuvastatin and copper-selenium nanoparticles were evaluated for their antibacterial activity, against Gram-positive and negative microorganisms, and anticancer efficacy, against MCF-7 and MDA-MB-231 cell lines. The results confirmed the potency of rosuvastatin calcium against cancer cells and the synergistic effect when loaded with smaller particle sizes of copper-selenium nanoparticles. This formulation holds a considerable potential for efficient breast cancer therapy.

Comparative Efficacy of Rosuvastatin Monotherapy and Rosuvastatin/Ezetimibe Combination Therapy on Insulin Sensitivity and Vascular Inflammatory Response in Patients with Type 2 Diabetes Mellitus.

BACKGRUOUND: Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM. METHODS: A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment. RESULTS: The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups. CONCLUSION: Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Degradation Mechanism Study for Secondary Degradants in Rosuvastatin Calcium and Determination of Degradant Acetaldehyde Using Static Headspace Gas Chromatography Coupled with Matrix Precipitation.

During the development of headspace gas chromatography (HSGC) method for assessing residual solvents in rosuvastatin calcium (RSV) drug substance, acetaldehyde (AA) was detected in obtained chromatograms, with a calculated concentration of up to 226 ppm. After a series of experiments, it was established that acetaldehyde originates from matrix interference due to direct degradation of Imp-C, which is accompanied by the formation of impurity at relative retention time (RRT) 2.18, without the involvement of impurity at RRT 2.31. The thermal instability of Imp-C also results in the formation of impurity at RRT 2.31 through dehydration and decarboxylation. In addition, cyclization reaction of degradant at RRT 2.18 further resulted in the generation of impurity at RRT 2.22. The structure of these three degradants, were confirmed by liquid chromatography-mass spectrometry (LC-MS), 1D and 2D nuclear magnetic resonance (NMR) measurement. In order to minimize the said matrix interference, a simple precipitation procedure was proposed as a pretreatment to mitigate the impact of Imp-C. Subsequently, an HSGC method was developed for the simultaneous determination of the degradant AA and the other five residual solvents used in RSV synthetic process. The final method was validated concerning precision, limit of detection (LOD) and limit of quantitation (LOQ), linearity, and accuracy.

The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study.

BACKGRUOUND: To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM). METHODS: This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints. RESULTS: A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (-63.90±6.89 vs. -55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, -8.47; 95% confidence interval, -16.44 to -0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of ß-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185). CONCLUSION: In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Lipid-Lowering Efficacy of Combination Therapy With Moderate-Intensity Statin and Ezetimibe Versus High-Intensity Statin Monotherapy: A Randomized, Open-Label, Non-Inferiority Trial From Korea.

Objective: This phase IV, multicenter, randomized controlled, open-label, and parallel clinical trial aimed to compare the efficacy and safety of ezetimibe and moderate intensity rosuvastatin combination therapy to that of high intensity rosuvastatin monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). Methods: This study enrolled patients with ASCVD and after a four-week screening period, patients were randomly assigned to receive either rosuvastatin and ezetimibe (RE 10/10 group) or high-intensity rosuvastatin (R20 group) only in a 1:1 ratio. The primary outcome was the difference in the percent change in the mean low-density lipoprotein cholesterol (LDL-C) level from baseline to 12 weeks between two groups after treatment. Results: The study found that after 12 and 24 weeks of treatment, the RE10/10 group had a greater reduction in LDL-C level compared to the R20 group (-22.9±2.6% vs. -15.6 ± 2.5% [p=0.041] and -24.2±2.5% vs. -12.9±2.4% [p=0.001] at 12 and 24 weeks, respectively). Moreover, a greater number of patients achieved the target LDL-C level of ≤70 mg/dL after the treatment period in the combination group (74.6% vs. 59.9% [p=0.012] and 76.2% vs. 50.8% [p<0.001] at 12 and 24 weeks, respectively). Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between two groups. Conclusion: Moderate-intensity rosuvastatin and ezetimibe combination therapy had better efficacy in lowering LDL-C levels without increasing adverse effects in patients with ASCVD than high-intensity rosuvastatin monotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03494270.

Utilization of response surface design for development and optimization of rosuvastatin calcium-loaded nano-squarticles for hair growth stimulating VEGF and IGF production: in-vitro and in-vivo evaluation.

INTRODUCTION: Countless individuals experience negative emotions as hair loss pattern affects their self-esteem and well-being. Rosuvastatin calcium (Ca-RUV) was reported to stimulate the growth of the hair in the applied area, hence, it was selected as a potential hair loss treatment drug. SIGNIFICANCE: This study aims to develop and optimize (Ca-RUV) loaded squarticles (SQRs) and assess their ability to deliver and release Ca-RUV in the hair follicle for the promotion of hair growth. METHODS: A response surface design was utilized to study the effect of varying Pluronic® F68 (PF68) and the percentage of liquid lipids within the core of the SQRs and the effects of particle size, entrapment efficiency, and drug released percentage after 24 h (%Q24) were assessed. The optimized formula was subjected to DSC, XRD, and in-vivo evaluation in rats. RESULTS: SQRs stabilized by 0.8% PF68 and contained 37.5% liquid lipids showed an acceptable particle size (250 nm), drug entrapment efficiency (75%), and %Q24 (100%). The in-vivo studies illustrated the ability of the formula to regrow hair in animals after 10 days due to the elevation of the vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) to their normal values and by 9% and 54%, respectively, relative to standard therapy minoxidil (5%). CONCLUSION: Thus, it can be concluded that the optimized formula of Ca-RUV loaded SQRs showed superior in-vivo results in the promotion of hair growth in a shorter period relative to the marketed product. Therefore, the formula can offer a viable option for the treatment of hair loss.

The Effects of 3-Month Rosuvastatin Adjuvant Therapy on Post Thrombotic Syndrome following Deep Vein Thrombosis; a Randomized Clinical Trial.

Introduction: Statins are known to have anticoagulation and anti-inflammatory effects. This study aimed to investigate the effect of Rosuvastatin in reduction of post thrombotic syndrome (PTS) following deep vein thrombosis (DVT). Methods: In this randomized clinical trial, patients who were diagnosed with DVT of lower extremity were randomly assigned to 4 treatment groups: group 1: Warfarin, group 2: Warfarin + Rosuvastatin, group 3: Rivaroxaban, and group 4: Rivaroxaban + Rosuvastatin. The treatments were followed for 3 months and prevalence of PTS (as primary outcome), as well as the changes in serum levels of D-dimer and C reactive protein (CRP), and the extent of thrombosis before and after the intervention (as secondary outcomes) were compared between groups. Results: 182 patients with the mean age of 55.22 ± 4.1 years finished the trial period (51.64% male). There was no significant difference between the groups regarding the baseline characteristics. Based on the Brandjes score, 31 (17.03%) patients had PTS at the end of the study. The occurrence of PTS was significantly lower in the groups taking statins (p<0.0001). Although the change in the mean difference of legs circumference before and after intervention, were significant in all groups (p < 0.05), the differences was more prominent in groups 2 and 4 (p < 0.0001). After 3 months of taking medication, decrease of CRP was more prominent in the statin groups (p = 0.001), and most cases with normal CRP were in statin groups. Among the patients with the serum D-dimer level above 10000 ng/mL, patients in the statin groups experienced significantly more reduction in D-dimer levels than the other groups (p<0.001). Conclusion: Rosuvastatin administration in combination with rivaroxaban or warfarin significantly reduces the level of inflammatory factors including CRP and D-dimer, compared to patients receiving anticoagulants alone. Rosuvastatin administration can significantly reduce the incidence of PTS and cause a difference in the size of the lower limbs within 3 months.

Comparison of the Efficacy of Atorvastatin and Rosuvastatin in Preventing Atrial Fibrillation after Coronary Artery Bypass Grafting: A Double-Blind Randomized Comparative Trial.

Background: Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by disorganized atrial activity and subsequent mechanical atrial failure. Postoperative AF is a frequent complication of coronary artery bypass grafting (CABG). Although there is evidence of decreased AF after CABG with statin usage, information is scarce regarding a direct comparison between atorvastatin and rosuvastatin. The present study was conducted to compare the efficacy of rosuvastatin and atorvastatin in preventing post-CABG AF. Methods: The present double-blind randomized comparative clinical trial selected CABG candidates with stable ischemic heart disease or acute coronary syndromes. Atorvastatin (40 mg per day) or rosuvastatin (20 mg per day) was prescribed 1 week before surgery, and the outcomes were compared. Results: Two-hundred patients, 100 cases in each group, completed the study. Twenty-five patients in each group were female, and the mean age was 59.30±8.42 years in the rosuvastatin group and 60.13±9.40 years in the atorvastatin group (P=0.513). The frequency of AF was 31% in the atorvastatin group and 27% in the rosuvastatin group (P=0.534). No significant differences existed between the groups concerning the length of hospital and ICU stay (P=0.333 and P=0.161) and in-hospital and 3-month mortality (P=0.315 and P=0.648). A subgroup analysis of only patients with stable ischemic heart disease could not detect a significant difference between the study groups in any of the investigated outcomes. Our logistic regression analysis showed an association only between age and the incidence of AF after CABG (OR, 1.12; 95% CI, 1.05 to 1.20; P<0.01). Conclusion: Rosuvastatin and atorvastatin are similar concerning the prevention of post-CABG AF, but there is a need for future well-designed multicenter studies on this topic.

Rosuvastatin treatment alone cannot alleviate lupus in murine model: a pilot study.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by the production of autoantibodies and high cholesterol levels. HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors have exhibited anti-inflammatory effects in several clinical trials. We conducted this study to evaluate the effect of rosuvastatin on inflammatory responses in lupus-prone mice. Methods: MRL/lpr mice were intraperitoneally injected with rosuvastatin (10 mg/kg, n=4) or vehicle (2% dimethyl sulfoxide, n=4) five times a week from 13 to 17 weeks of age. The serum levels of low-density lipoprotein (LDL) cholesterol and autoantibodies were measured, as well as the urine levels of albumin. Renal tissues were stained for histopathological analysis. Concentrations of key inflammatory cytokines were measured in the serum, and messenger RNA (mRNA) levels in target organs (kidney, spleen, and lymph nodes) were evaluated. Results: Rosuvastatin treatment significantly decreased serum LDL cholesterol concentration in MRL/lpr mice. However, the clinical manifestations and autoantibody titres did not improve with rosuvastatin treatment. In addition, serum inflammatory cytokines and proteinuria did not change. Histopathological analysis of the kidneys revealed no improvement. When assessing the expression of mRNA, treatment with rosuvastatin decreased tumor necrosis alpha and interleukin-17 concentration in spleen and kidney tissue and in the kidneys and lymph nodes of MRL/lpr mice, respectively. Conclusion: Although it can decrease inflammatory cytokines in the lymphoid organs and kidneys of MRL/lpr mice, treatment with rosuvastatin is insufficient to alleviate SLE.

Dose study of rosuvastatin calcium in the treatment of coronary heart disease and hyperlipidemia.

OBJECTIVE: To study the clinical efficacy of different doses of rosuvastatin to treat elderly patients with senile coronary heart disease and hyperlipidemia. METHODS: By means of retrospective analysis, 150 elderly patients with coronary heart disease and hyperlipidemia who were treated in Zhangjiakou First Hospital from January 2020 to December 2020 were selected as the study subjects. They were divided into three groups (50 patients in each group) according to the different treatment methods. All patients were given routine treatment for coronary heart disease and hyperlipidemia. At the same time, group A got 5 mg of rosuvastatin calcium per day, group B got 10 mg and group C got C, 20 mg. After 4 months of continuous treatment, changes of blood lipid level, inflammatory factors, and cardiac function in the three groups were compared before and after treatment. Finally, the incidence of adverse reactions in the three groups was statistically compared. RESULTS: After 4 months of treatment, the levels of TC, LDL, and TG in group B were significantly lower than those of group A, and the levels of HDL were significantly higher than those in group A (P<0.05). There was no significant difference of the above indicators between groups B and C after 4 months of treatment (P>0.05). Using 2 months, 3 months, and 4 months of therapy as time points, the blood lipid levels of the B and C groups was lower than in group A (P<0.05); Serum hs-CRP and TNF of patients in group B and group C after 4 months of treatment were significantly lower than those of group A (P<0.05); The LVEF comparison between groups showed that C was higher than A (P<0.05); The occurrence rate between adverse reactions during the 4 months of medication did not have statistical significance (P>0.05). CONCLUSION: Rosuvastatin calcium canimprove the clinical symptoms of elderly patients with coronary heart disease complicated by hyperlipidemia, and can improve the blood lipid level, cardiac function and the level of inflammatory factors in the body, but the clinical effect is not significantly improved by increasing the application dose. This suggests that the daily application dose should be 10 mg.

The Use of Calcium Phosphate-Based Starter Pellets for the Preparation of Sprinkle IR MUPS Formulation of Rosuvastatin Calcium.

Sprinkle formulations represent an interesting concept of medicinal products aimed at the steadily growing population of patients suffering from swallowing difficulties (dysphagia). In the present work, immediate-release sprinkle MUPS (multiple-unit pellet system) containing rosuvastatin calcium as a model drug substance was successfully developed. The formulation was prepared by drug layering technique using novel calcium phosphate-based starting pellets (PharSQ® Spheres CM) of three different particle sizes. The study showed that the developed multiparticulates were characterized by uniform distribution of coating layers thickness, as well as fast dissolution rate (more than 85% of rosuvastatin calcium dissolved within 30 min, as required by the relevant USP/NF monograph). Rosuvastatin calcium, like other statins, has a bitter, unpleasant taste. Investigations conducted with an electronic tongue suggested that the developed formulation achieved the desired taste-masking efficiency. The effect was found to be particle size-dependent, improving as the size of the multiparticulates increased.

Green-assisted spectrophotometric techniques utilizing mathematical and ratio spectra manipulations to resolve severely overlapped spectra of a cardiovascular pharmaceutical mixture.

Cardiovascular diseases, in particular hypertension and hypercholesterolemia, are two of the main causes of death worldwide. These conditions are silent killer syndromes that need a variety of pharmacological treatments to be effectively controlled. This study introduces novel, environmentally friendly spectrophotometric techniques for the simultaneous determination of telmisartan (TMS) and rosuvastatin calcium (RVS) in their pharmaceutical dosage forms. For the simultaneous determination of the binary mixture, the suggested methods included the dual wavelength method (DWM) which utilizes mainly the absorbance difference at 233 nm and 253 for TMS determination and, the absorbance difference at 274 nm and 310 for RVS determination as the selected wavelengths for each drug is directly proportional to the drug of interest independent on the other interfering component. The Fourier-self deconvolutions method (FSDM) depends on compressing their bandwidth to resolve the overlap. Ratio difference spectrophotometric method (RDSM) that utilizes TMS 35 µg.mL-1 and RVS 20 µg.mL-1, respectively as divisors to produce the ratio spectra for each drug. Further manipulation of the produced ratio spectra was applied for the determination of the two drugs. Mean centering method (MCM) where a suitable wavelength range was chosen to exclusively use the informative portions and prevent experimental spectrum noises. The investigated methods showed good levels of detection and quantification together with excellent linearity. The suggested methods' greenness was evaluated using two different greenness evaluation tools, which showed that the methods were green in terms of several factors, including the safety of the chemicals, instruments, and waste. The validity of the methodologieswas investigated by resolving prepared laboratory mixtureswith varying TMS and RVS ratios. The standard addition method also assured the newly added methods. Finally, statistical analysis using the reported method did not reveal any appreciable differences in terms of accuracy and precision. The developed methods can be employed in quality control laboratories to ascertain the binary mixture due to their high precision and affordability.

Influence of rosuvastatin on apolipoproteins and coagulation factor levels: Results from the STAtin Reduce Thrombophilia trial.

Background: The STAtins Reduce Thrombophilia trial showed that, in patients with prior venous thrombosis, rosuvastatin decreased various coagulation factor levels. Objectives: Here, we investigated the hypothesis that statins decrease coagulation factor levels through shared mechanisms of synthesis or regulatory pathways with apolipoproteins. Methods: We measured the levels of apolipoprotein (Apo)A-I, A-II, A-IV, (a), B-100, B-total, C-I, C-II, C-III, and E in patients (n = 126) randomized to 28 days of rosuvastatin use. We assessed the association between apolipoproteins and coagulation factors at baseline using linear regression. The mean difference in apolipoprotein levels between baseline and after 28 days of rosuvastatin use was determined through linear regression, adjusting for age, sex, and body mass index. Coagulation factors were added to this model to determine if the lowering of apolipoproteins by rosuvastatin was linked with coagulation factor levels. Results: At baseline, levels of all apolipoproteins, except Apo(a), were positively associated with FVII, FIX, and FXI. Apolipoproteins levels, except for ApoA-I, A-IV, and Apo(a), were decreased after 28 days of rosuvastatin. ApoB-100 showed the largest mean decrease of -0.43 g/L (95% CI = -0.46 to -0.40). The decrease in ApoC-I and C-III levels was associated with a decrease in FVII, whereas the decrease in apoA-II, B-100, and B-total was associated with a decrease in FXI. The decrease in apolipoproteins was neither associated with FVIII or vWF decrease nor with endogenous thrombin potential changes. Conclusions: Rosuvastatin decreases the level of several apolipoproteins, but this decrease was associated only with a decrease in FVII and XI and not with FVIII/vWF.

Fabrication and characterization of orodispersible films loaded with solid dispersion to enhance Rosuvastatin calcium bioavailability.

The present study was aimed to formulate and evaluate fast dissolving oral film of Rosuvastatin calcium to improve its bioavailability in comparison to typical solid oral dosage forms. The drug was formulated as solid dispersion with hydrophilic polymers and assessed for different constraints such as drug content, saturated solubility, and drug-polymer interaction. Best formula was selected and prepared in the form of orodispersible film. The films were developed by solvent casting method and examined for weight variations, drug content, folding endurance, pH, swelling profile, disintegration time, and in vitro dissolution. Further pharmacokinetic study was also performed on rabbit and compared with that of the marketed oral formulation. The drug and the polymers were found to be compatible with each other by FTIR study. Maximum solubility was found at drug polymer ratio of 1:4 and that was 54.53 ± 2.05 µg/mL. The disintegration time of the developed film was observed to be 10 ± 2.01 s, while release of the Rosuvastatin from the film was found to be 99.06 ± 0.40 in 10 min. Stability study shown that developed film was stable for three months. Further pharmacokinetic study revealed that developed orodispersible film had enhance oral bioavailability as compared to marketed product (Crestor® tablets). Conclusively, the study backs the development of a viable ODF of Rosuvastatin with better bioavailability.

Chemo- and enantio-selective reversed-phase HPLC analysis of rosuvastatin using a cellulose-based chiral stationary phase in gradient elution mode.

A direct reversed-phase high-performance liquid chromatographic (HPLC) method was developed for determining the content of the enantiomeric impurity of the chiral statin rosuvastatin calcium salt (RSV) in commercial tablets. The baseline enantioseparation was achieved using the Lux Cellulose-2 column and a binary linear gradient of acetonitrile and trifluoroacetic acid 0.05% in an aqueous solution. The flow rate of the mobile phases and column temperature were set at 1.0 mL min- 1 and 40 °C, respectively. In comparison with the isocratic HPLC method reported in the European Pharmacopoeia (EP) monograph for RSV, the gradient elution method offered improved chemo-and enantio-selectivity and reduced analysis times. The limits of quantitation and detection of the enantiomeric impurity were found to be 0.15 and 0.05 µg mL-1.

A Novel Validated UHPLC Method for the Estimation of Rosuvastatin and Its Complete Impurity Profile in Tablet Formulations.

A key step in the development of medicinal products is the research and validation of selective and sensitive analytical methods for the control of impurities from synthesis and degradation. As most impurities are similar in structure to the drug substance, the achievement of chemo-selective conditions is usually challenging. Herein, a direct and highly selective ultra-high-performance liquid chromatographic method for determining the assay and related substances content in medicinal products containing rosuvastatin calcium salt (RSV) is presented. RSV is used to treat high cholesterol levels and prevent heart attacks and strokes. The most engaging feature of this method was the baseline separation of all organic related substances listed in the European Pharmacopoeia (EP) monograph for the RSV tablets, achieved for the first time in less than 15 min using the Acquity BEH C18 (100 mm × 2.1 mm, 1.7 µm) column under reversed-phase isocratic conditions. The mobile phase adopted for the chemo-selective analysis does not contain buffers but instead contains trifluoroacetic as an acid additive. The chromatographic method was validated according to the guidelines of the International Conference on Harmonization (ICH) and proved to be linear, precise and accurate for determining the content of RSV and related chiral substances in tablet formulations.

Is rosuvastatin protective against sepsis-associated encephalopathy? A secondary analysis of the SAILS trial.

BACKGROUND: Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy (SAE) is a major complication. Rosuvastatin may play a neuroprotective role due to its protective effects on the vascular endothelium and its anti-inflammatory functions. Our study aimed to explore the potential protective function of rosuvastatin against SAE. METHODS: Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the "Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome" study (SAILS trial, ClinicalTrials.gov number: NCT00979121). Patients were divided into rosuvastatin and placebo groups. This is a secondary analysis of the SAILS dataset. Baseline characteristics, therapy outcomes, and adverse drug events were compared between groups. RESULTS: A total of 86 patients were eligible for our study. Of these patients, 51 were treated with rosuvastatin. There were significantly fewer cases of SAE in the rosuvastatin group than in the placebo group (32.1% vs. 57.1%, P=0.028). However, creatine kinase levels were significantly higher in the rosuvastatin group than in the placebo group (233 [22-689] U/L vs. 79 [12-206] U/L, P=0.034). CONCLUSION: Rosuvastatin appears to have a protective role against SAE but may result in a higher incidence of adverse events.

Tailoring of Rosuvastatin Calcium and Atenolol Bilayer Tablets for the Management of Hyperlipidemia Associated with Hypertension: A Preclinical Study.

Hyperlipidemia is still the leading cause of heart disease in patients with hypertension. The purpose of this study is to make rosuvastatin calcium (ROS) and atenolol (AT) bilayer tablets to treat coexisting dyslipidemia and hypertension with a single product. ROS was chosen for the immediate-release layer of the constructed tablets, whereas AT was chosen for the sustained-release layer. The solid dispersion of ROS with sorbitol (1:3 w/w) was utilized in the immediate-release layer while hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC), and sodium bicarbonate were incorporated into the floating sustained-release layer. The concentrations of HPMC and EC were optimized by employing 32 full factorial designs to sustain AT release. The bilayer tablets were prepared by the direct compression method. The immediate-release layer revealed that 92.34 ± 2.27% of ROS was released within 60 min at a pH of 1.2. The second sustained-release layer of the bilayer tablets exhibited delayed release of AT (96.65 ± 3.36% within 12 h) under the same conditions. The release of ROS and AT from the prepared tablets was found to obey the non-Fickian diffusion and mixed models (zero-order, Higuchi and Korsmeyer-Peppas), respectively. Preclinical studies using rabbit models investigated the impact of ROS/AT tablets on lipid profiles and blood pressure. A high-fat diet was used to induce obesity in rabbits. Bilayer ROS/AT tablets had a remarkable effect on decreasing the lipid profiles, slowing weight gain, and lowering blood pressure to normal levels when compared to the control group.