Search Results (24)

Stability assessments of drug substances and the detection of crystalline forms are critical for ensuring drug quality and medication safety. Atorvastatin calcium drug substance samples were characterized using powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). DSC results demonstrated a precise discrimination of the stability of samples. An analysis of PXRD characteristic peaks and DSC melting data suggested that instability likely stems from the presence of the amorphous phase. To validate this hypothesis, blended samples containing controlled ratios of amorphous phase and crystalline Form I were prepared. Quantitative models based on PXRD, DSC, and near-infrared spectroscopy (NIRS) data were developed to predict amorphous content, and classification accuracy was evaluated. Experimental results confirmed that all three models achieved classification accuracy values exceeding 70% in the stability prediction of the two groups of samples, which included “stable” and “unstable” samples, substantiating the hypothesis. Among them, the modeling method based on NIRS data was not only non-destructive and rapid but also demonstrates a superior discrimination accuracy value reaching 100% (n = 11), showing potential for promotion and application in industrial sample detection. The quantitative correlation between amorphous content and stability was successfully established in this study, offering a novel method for a quality stability assessment of atorvastatin calcium drug substances. Full article

Atorvastatin calcium, an antifungal agent, has the potential to be repositioned/repurposed to combat the increasing antimicrobial resistance. However, one of the most crucial issues in developing atorvastatin calcium-loaded products with a topical antifungal effect is achieving the optimal release and dissolution rates of this statin to produce the desired therapeutic effect. In this paper, we report on the development and pharmaceutical assessment of hydrogels composed of low-molecular-weight chitosan, tragacanth, and xanthan gum/pectin/κ-carrageenan as potential drug carriers for atorvastatin calcium for buccal delivery. Multidirectional analysis of the carriers with regard to their drug-release profiles and mucoadhesive, antimicrobial, and cytotoxic properties was accompanied by an evaluation of the freeze-drying process used to improve the hydrogels’ applicability. Using differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy techniques, the role of lyophilization in enhancing atorvastatin calcium delivery from polyelectrolyte complex-based matrices via drug amorphization was demonstrated. The freeze-dried hydrogels had significantly improved release and dissolution rates for the amorphic statin. Therefore, there is great potential for the use of lyophilization in the design of polyelectrolyte complex-based semi-solids in usable dosage forms for numerous crystalline and poorly water-soluble active substances. Full article

Background/Objectives: The gold standard in the non-surgical treatment of periodontitis is scaling and root planning (SRP). In recent years, studies have emerged suggesting additional clinical benefits from the use of statins as an adjunct to classical periodontal disease treatment. The aim of the present study was to review the relevant literature relating to the subgingival use of statins as an adjunctive treatment to the classical, non-surgical treatment of periodontitis, with a particular focus on groups with general factors that may affect the outcome of treatment. Methods: The authors conducted a systematic review following the PRISMA 2020 guidelines. The electronic literature search conducted included the MEDLINE (PubMed) database, Web of Science, Scopus, and Google Scholar from 1 January 2012 to 14 June 2024. The keywords used for the PubMed search were determined with the help of the MeSH Browser Tool and were as follows: Periodontitis [Mesh] AND Statin [Mesh] OR Simvastatin [Mesh] OR Atorvastatin [Mesh] or Rosuvastatin Calcium [Mesh]. Based on the authors’ inclusion and exclusion criteria, 20 results were included in the review, out of 937. Results: The improvement was more pronounced in patients without systematic diseases compared to those with type II diabetes and in non-smokers compared to smoking patients. Greater improvements in clinical and radiological parameters were seen in patients diagnosed with aggressive periodontitis compared to patients with chronic periodontitis. Conclusions: This literature review led the authors to the conclusion that statins applied locally might be competent agents for improving the therapeutic outcomes of SRP. Full article

The objective of this work was to develop a supersaturated gel formulation (SGF) loaded with the maximum atorvastatin calcium trihydrate (ATR) dose. The maximum dose strength of ATR needs to be reduced through improving solubility and dissolution rate to mitigate side effects due to the necessity of taking high doses. ATR has highly pH-dependent solubility at 37 °C, leading to poor solubility (<10 μg/mL) in stomach acid (pH 1.2). Among the various molecular weights of polyethylene glycols (PEGs) and surfactants, PEG 200 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were selected as the solubilizer and precipitation inhibitor for ATR, respectively. PEG 200 demonstrated very high solubility for ATR (>60%, w/w), and the combined use of TPGS and PEG 200 formed an organogel state and suppressed ATR precipitation, showing 15-fold higher dispersion solubility in buffer solution at pH 1.2 compared to the formulation with PEG 200 alone. The optimal SGF composition (ATR/PEG 200/TPGS = 10/60/30, w/w) exhibited an over 95% dissolution rate within 2 h at pH 1.2, compared to less than 50% for the original commercial product. In a transmission electron microscope analysis, the SGF suppressed ATR precipitation and revealed smaller precipitated particles (<300 nm) compared to the control samples. In the XRD analysis, the SGF was physically stable for 100 days at room temperature without the recrystallization of ATR. In conclusion, the SGF suggested in this work would be an alternative formulation for the treatment of dyslipidemia with enhanced solubility, dissolution, and physical stability. Full article

Objectives: Isostrictiniin (ITN), a natural polyphenol extracted from Nymphaea candida (snow-white waterlily), has antioxidant and hepatoprotective activities that may be beneficial in treating metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to investigate the protective effects of ITN on high-fat, high-sugar diet (HFSD)-induced steatosis in MASLD mice and its mechanisms. Methods: Kunming mice were randomly divided into normal control and HFSD groups. After being fed for 4 weeks, the HFSD group was randomly divided into model, atorvastatin calcium (ATC; 10 mg/kg), and ITN (25, 50, and 100 mg/kg) groups. After continued feeding for 4 weeks, the biochemical indexes in the mice were determined. Results: Compared with the model group, the liver index; FBG; HOMA-IR; serum AST, ALT, TG, TC, and LDL-C; and liver MDA, IL-6, TNF-α, and IL-1β levels in the ITN (25, 50, and 100 mg/kg) and ATC (10 mg/kg) groups were significantly decreased (p < 0.05), while serum HDL-C and liver SOD and GSH-Px levels were increased (p < 0.05). Pathological observation showed that ITN treatment mitigated the lipid liver deposition in the HFSD mice. Moreover, ITN could upregulate liver-tissue p-AMPK/AMPK protein expression in the HFSD-induced MASLD mice and downregulate SREBP-1c and ACC levels (p < 0.05). Conclusions: ITN can significantly improve MASLD mice, and its mechanism may be related to the regulation of the AMPK/SREBP-1c/ACC pathway. Full article

Little is known about the effects of statins, which are cholesterol-lowering drugs, on the bioenergetic functions of mitochondria in the brain. This study aimed to elucidate the direct effects of atorvastatin and simvastatin on the bioenergetics of isolated rat brain mitochondria by measuring the statin-induced changes in respiratory chain activity, ATP synthesis efficiency, and the production of reactive oxygen species (ROS). Our results in isolated brain mitochondria are the first to demonstrate that atorvastatin and simvastatin dose-dependently significantly inhibit the activity of the mitochondrial respiratory chain, resulting in a decreased respiratory rate, a decreased membrane potential, and increased ROS formation. Moreover, the tested statins reduced mitochondrial coupling parameters, the ADP/O ratio, the respiratory control ratio, and thus, the oxidative phosphorylation efficiency in brain mitochondria. Among the oxidative phosphorylation complexes, statin-induced mitochondrial impairment concerned complex I, complex III, and ATP synthase activity. The calcium-containing atorvastatin had a significantly more substantial effect on isolated brain mitochondria than simvastatin. The higher inhibitory effect of atorvastatin was dependent on calcium ions, which may lead to the disruption of calcium homeostasis in mitochondria. These findings suggest that while statins are effective in their primary role as cholesterol-lowering agents, their use may impair mitochondrial function, which may have consequences for brain health, particularly when mitochondrial energy efficiency is critical. Full article

The aim of this study was to investigate the effects of aflatoxin B₁ (AFB₁) on cholestasis in duck liver and its nutritional regulation. Three hundred sixty 1-day-old ducks were randomly divided into six groups and fed for 4 weeks. The control group was fed a basic diet, while the experimental group diet contained 90 μg/kg of AFB₁. Cholestyramine, atorvastatin calcium, taurine, and emodin were added to the diets of four experimental groups. The results show that in the AFB₁ group, the growth properties, total bile acid (TBA) serum levels and total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) liver levels decreased, while the malondialdehyde (MDA) and TBA liver levels increased (p < 0.05). Moreover, AFB₁ caused cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin could reduce the TBA serum and liver levels (p < 0.05), alleviating the symptoms of cholestasis. The qPCR results show that AFB₁ upregulated cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and cytochrome P450 family 8 subfamily B member 1 (CYP8B1) gene expression and downregulated ATP binding cassette subfamily B member 11 (BSEP) gene expression in the liver, and taurine and emodin downregulated CYP7A1 and CYP8B1 gene expression (p < 0.05). In summary, AFB₁ negatively affects health and alters the expression of genes related to liver bile acid metabolism, leading to cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin can alleviate AFB₁-induced cholestasis. Full article

Atorvastatin (ATV) is a well-established lipid-lowering agent. ATV has two stereogenic centers, and of the four possible stereoisomers, only the (3R,5R) form is used therapeutically. The European Pharmacopoeia (EP) monograph 2022 for ATV calcium salt describes a normal-phase high-performance liquid chromatography (HPLC) method for the determination of enantiomeric purity in both drug substance and working standard samples, based on a 150 mm × 4.6 mm Chiralpak AD-H column. The main problems with this method are the very long analysis time and the high solvent consumption. Here, an alternative chromatographic protocol was developed using the Chiralpak AD-3 column (250 mm × 4.6 mm) packed with 3 μm silica particles instead of the 5 μm silica particles of the Chiralpak AD-H chiral stationary phase and characterized by the same polysaccharide selector, amylose-tris(3,5-dimethylphenylcarbamate). Using a mobile phase consisting of a mixture of n-hexane-ethanol-formic acid 90:10:0.1 (v/v/v) as the mobile phase and setting the flow rate and column temperature to 1.0 mL min⁻¹ and 35 °C, respectively, a simultaneous stereo-selective separation was achieved within 35 min without observing any overlap between the enantiomeric impurity peak and peaks related to other ATV impurities. Compared to HPLC EP conditions, the analysis time to elute all the potentially related substances was faster and significantly less mobile phase volume was required. The linearity of the method has been demonstrated in the range of 4.4 μg mL⁻¹ to 1000 μg mL⁻¹ (R² > 0.999). At a concentration of 4.4 μg mL⁻¹, which is 0.075% of the test solution (5.8 mg mL⁻¹, as ATV free acid), the signal-to-noise ratio was found to be 20. Full article

The objective of this study was to develop a versatile lipid core for the ‘brick-dust type of drugs’ (poorly water-soluble and poorly lipid-soluble drugs). In the first step, excipients of different polarities were classified according to their behavior in aqueous solutions. Subsequently, binary mixtures were prepared with cetyl palmitate (Crodamol™ CP pharma, Campinas, São Paulo, Brazil) as the solid lipid, and its miscibility with other excipients was evaluated using Raman mapping and classical least squares (CLS). Based on the results, the excipients Crodamol™ CP pharma (hydrophobic), Super Refined™ DMI (dimethyl isosorbide; hydrophilic, Mill Hall, PA, USA), and Super Refined™ Lauryl Lactate (lauryl lactate, medium polarity, Mill Hall, PA, USA) were chosen to compose the lipid core. The ideal proportion of these excipients was determined using a mixture design and the standard deviation (STD) of image histograms as the response variables. After statistical evaluation of the DoE results, the final composition was determined, and drugs with different logP (0 to 10) and physicochemical characteristics were evaluated in the optimized mixture. The drugs butamben (Sigma-Aldrich Co., Spruce Street, St. Louis, MO, USA), tacrolimus (NutriFarm, São Paulo, Brazil), atorvastatin calcium, and resveratrol (Botica da Terra, Campinas, Brazil) presented a homogeneous distribution in the optimized lipid core, indicating that this is a promising system to be used in nanostructured lipid carrier (NLC) formulations of such types of drugs. Full article

Nowadays, smoking and tobacco-related habits (chewing tobacco) are recognized as the most frequent environmental risk factor for periodontal disorders. Atorvastatin calcium (ATV) is a well-known lipid-lowering drug, but recent studies have discussed its pleiotropic effects, including anti-inflammatory properties, anti-bacterial properties, etc. This anti-inflammatory effect can be studied as an adjunct for scaling and root planing (a non-surgical process to remove dental tartar and smooth root surfaces) for periodontic problems. The goal of the study is to formulate and evaluate ATV-niosomes, introduce them in a gel-based formulation by utilizing an appropriate gelling agent, and evaluate them for various parameters. The niosomal vesicles were prepared using the thin-film hydration method. Gel was prepared using the dispersion method, and an in vitro drug release study was conducted using a Franz diffusion cell. According to the results evaluated, ATV niosomal gels loaded with different concentrations of Carbopol 934 were effectively produced utilizing ATV-niosomes that were formulated through the thin-film hydration process using cholesterol and Span 60. The ATV-niosomes showed the highest entrapment efficiency, up to 84%, and the zeta potential (−18 mV) and PDI (0.106) showed stable and homogenous behavior in the vesicles formed. The performance of the optimized gel containing 1% Carbopol 934 showed in vitro release of up to 8 h following zero-order release. The gel also proved to have antimicrobial activity against S. aureus and P. aeruginosa. Therefore, we conclude that 1% Carbopol 934 gel comprising ATV-niosomes showed a prolonged effect compared to plain ATV and can effectively work to improve the periodontal condition as an adjunct to scaling and root planing. Full article

Background and Objectives: We have recently reported that Fluvastatin, Atorvastatin, Simvastatin and Rosuvastatin have calcium channel antagonistic activities using rabbits’ intestinal preparations. The current study is focused on the effects of Pitavastatin and Lovastatin for possible inhibition of vascular L-Type calcium channels, which may have vasorelaxant effect(s). Combined effects of Pitavastatin and Lovastatin in the presence of Amlodipine were also tested for vasorelaxation. Materials and Methods: Possible relaxing effects of Pitavastatin and Lovastatin on 80 mM Potassium chloride (KCL)-induced contractions and on 1 µM norepinephrine (N.E)-induced contractions were studied in isolated rabbit’s aortic strips preparations. Relaxing effects on 80 mM KCL-induced vascular contractions were further verified by constructing Calcium Concentration Response Curves (CCRCs), in the absence and presence of three different concentrations of Pitavastatin and Lovastatin using CCRCs as negative control. Verapamil was used as a standard drug that has L-Type calcium channel binding activity. In other series of experiments, we studied drug interaction(s) among Pitavastatin, Lovastatin, and amlodipine. Results: The results of this study imply that Lovastatin is more potent than Pitavastatin for having comparatively lower EC₅₀ (7.44 × 10⁻⁵ ± 0.16 M) in intact and (4.55 × 10⁻⁵ ± 0.10 M) in denuded aortae for KCL-induced contractions. Lovastatin amplitudes in intact and denuded aortae for KCL-induced contractions were, respectively, 24% and 35.5%; whereas amplitudes for Pitavastatin in intact and denuded aortae for KCL-induced contractions were 34% and 40%, respectively. A left shift in the EC₅₀ values for the statins was seen when we added amlodipine in EC₅₀ (Log Ca⁺⁺ M). Right shift for CCRCs state that Pitavastatin and Lovastatin have calcium channel antagonistic effects. Lovastatin in test concentration (6.74 × 10⁻⁷ M) produced a right shift in relatively lower EC₅₀ (−2.5 ± 0.10) Log Ca⁺⁺ M as compared to Pitavastatin, which further confirms that lovastatin is relatively more potent. The right shift in EC₅₀ resembles the right shift of Verapamil. Additive effect of Pitavastatin and Lovastatin was noted in presence of amlodipine (p < 0.05). Conclusions: KCL (80 mM)-induced vascular contractions were relaxed by Pitavastatin and Lovastatin via inhibitory effects on L-Type voltage-gated calcium channels. Lovastatin and Pitavastatin also relaxed Norepinephrine (1 µM)-induced contractions giving an insight for involvement of dual mode of action of Pitavastatin and Lovastatin. Full article

Background and Objectives: We have recently reported that stains have calcium channel blocking activity in isolated jejunal preparations. In this study, we examined the effects of atorvastatin and fluvastatin on blood vessels for a possible vasorelaxant effect. We also studied the possible additional vasorelaxant effect of atorvastatin and fluvastatin, in the presence of amlodipine, to quantify its effects on the systolic blood pressure of experimental animals. Materials and Methods: Atorvastatin and fluvastatin were tested in isolated rabbits’ aortic strip preparations using 80mM Potassium Chloride (KCl) induced contractions and 1 micro molar Norepinephrine (NE) induced contractions. A positive relaxing effect on 80 mM KCl induced contractions were further confirmed in the absence and presence of atorvastatin and fluvastatin by constructing calcium concentration response curves (CCRCs) while using verapamil as a standard calcium channel blocker. In another series of experiments, hypertension was induced in Wistar rats and different test concentrations of atorvastatin and fluvastatin were administered in their respective EC₅₀ values to the test animals. A fall in their systolic blood pressure was noted using amlodipine as a standard vasorelaxant drug. Results: The results show that fluvastatin is more potent than amlodipine as it relaxed NE induced contractions where the amplitude reached 10% of its control in denuded aortae. Atorvastatin relaxed KCL induced contractions with an amplitude reaching 34.4% of control response as compared to the amlodipine response, i.e., 39.1%. A right shift in the EC₅₀ (Log Ca++ M) of Calcium Concentration Response Curves (CCRCs) implies that statins have calcium channel blocking activity. A right shift in the EC₅₀ of fluvastatin with relatively less EC₅₀ value (−2.8 Log Ca++ M) in the presence of test concentration (1.2 × 10⁻⁷ M) of fluvastatin implies that fluvastatin is more potent than atorvastatin. The shift in EC₅₀ resembles the shift of Verapamil, a standard calcium channel blocker (−1.41 Log Ca++ M). Conclusions: Atorvastatin and fluvastatin relax the aortic strip preparations predominantly through the inhibition of voltage gated calcium channels in high molar KCL induced contractions. These statins also inhibit the effects of NE induced contractions. The study also confirms that atorvastatin and fluvastatin potentiate blood pressure lowering effects in hypertensive rats. Full article

Calcium oxalate (CaOx) is the major constituent of kidney stones. Growing evidence shows a close connection between hyperlipidemia, cardiovascular disease (CVD), and the formation of kidney stones. Owing to their antioxidant properties, statins control hyperlipidemia and may ameliorate CaOx stone formation. The present study was designed to investigate the suppressive effects of statins on CaOx urolithiasis and their potential mechanism. We used rats fed a high-fat diet (HFD) to achieve hyperlipidemia (HL) and hydroxyproline (HP) water to establish a hyperoxaluric CaOx nephrolithiasis model; the animals were administered statins (A) for 28 days. The rats were divided into eight groups treated or not with A, i.e., Control, HP, HL, HL + HP. HL aggravated urinary calcium crystallization compared to the control. Due to increased expression of renal osteopontin (OPN), a key anti-lithic protein, and reduced free radical production, the calcium crystals in the urinary bladder increased as renal calcium deposition decreased. The levels of the ion activity product of CaOx (AP(CaOx)) decreased after statins administration, and AP(Calcium phosphate) (CaP) increased, which suggested the dominant calcium crystal composition changed from CaOx to CaP after statin administration. In conclusion, atorvastatin decreases renal CaOx stone deposits by restoring OPN expression in hyperoxaluric rats fed a HFD. Full article

Geriatric patients are more likely to suffer from multiple chronic diseases that require using several drugs, which are commonly ingested. However, to enhance geriatric patients’ convenience, the electrospun nanofiber system was previously proven to be a successful alternative for the existing oral dosage forms, i.e., tablets and capsules. These nanofibers prepared either as single- or multi-layered fibers could hold at least one active compound in each layer. They might also be fabricated as ultra-disintegrated fibrous films for oral cavity administration, i.e., buccal or sublingual, to improve the bioavailability and intake of the administered drugs. Therefore, in this work, a combination of nifedipine and atorvastatin calcium, which are frequently prescribed for hypertension and hyperlipidemia patients, respectively, was prepared in a coaxial electrospinning system for buccal administration. Scanning electron microscopy image showed the successful preparation of smooth, non-beaded, and non-porous surfaces of the drug-loaded nanofibers with an average fiber diameter of 968 ± 198 nm. In contrast, transmission electron microscopy distinguished the inner and outer layers of those nanofibers. The disintegration of the drug-loaded nanofibers was ≤12 s, allowing the rapid release of nifedipine and atorvastatin calcium to 61% and 47%, respectively, after 10 min, while a complete drug release was achieved after 120 min. In vitro, a drug permeation study using Franz diffusion showed that the permeation of both drugs from the core–shell nanofibers was enhanced significantly (p < 0.05) compared to the drugs in a solution form. In conclusion, the development of drug-loaded nanofibers containing nifedipine and atorvastatin calcium can be a potential buccal delivery system. Full article

Electroporation is influenced by the features of the targeted cell membranes, e.g., the cholesterol content and the surface tension of the membrane. The latter is eventually affected by the organization of actin fibers. Atorvastatin is a statin known to influence both the cholesterol content and the organization of actin. This work analyzes the effects of the latter on the efficacy of electroporation of cancer cells. In addition, herein, electroporation was combined with calcium chloride (CaEP) to assess as well the effects of the statin on the efficacy of electrochemotherapy. Cholesterol-rich cell lines MDA-MB231, DU 145, and A375 underwent (1) 48 h preincubation or (2) direct treatment with 50 nM atorvastatin. We studied the impact of the statin on cholesterol and actin fiber organization and analyzed the cells’ membrane permeability. The viability of cells subjected to PEF (pulsed electric field) treatments and CaEP with 5 mM CaCl₂ was examined. Finally, to assess the safety of the therapy, we analyzed the N-and E-cadherin localization using confocal laser microscopy. The results of our investigation revealed that depending on the cell line, atorvastatin preincubation decreases the total cholesterol in the steroidogenic cells and induces reorganization of actin nearby the cell membrane. Under low voltage PEFs, actin reorganization is responsible for the increase in the electroporation threshold. However, when subject to high voltage PEF, the lipid composition of the cell membrane becomes the regulatory factor. Namely, preincubation with atorvastatin reduces the cytotoxic effect of low voltage pulses and enhances the cytotoxicity and cellular changes induced by high voltage pulses. The study confirms that the surface tension regulates of membrane permeability under low voltage PEF treatment. Accordingly, to reduce the unfavorable effects of preincubation with atorvastatin, electroporation of steroidogenic cells should be performed at high voltage and combined with a calcium supply. Full article