Simvastatin Content Research Articles

Carboxymethyl cellulose/sodium alginate hydrogel with anti-inflammatory capabilities for accelerated wound healing; In vitro and in vivo study

Recently, managing the chronic skin wounds has become increasingly challenging for healthcare professionals due to the intricate orchestration of cellular and molecular processes involved that lead to the uncontrollable inflammatory reactions which hinder the healing process. Therefore, different types of wound dressings with immunomodulatory properties have been developed in recent years to effectively regulate the immune responses, enhance angiogenesis, promote re-epithelialization, and accelerate the wound healing process. This study aims to develop a new type of immunomodulatory wound dressing utilizing carboxymethyl cellulose (CMC)/sodium alginate (Alg)-simvastatin (SIM) to simultaneously enhance the inflammatory responses and the wound healing ratio. The CMC/Alg-SIM hydrogels exhibited appropriate swelling ratio, water vapor transmission rate, and desirable degradation rate, depending on the SIM content. The fabricated dressing showed sustained release of SIM (during 5 days) that improved the proliferation of skin cells. According to the in vitro findings, the CMC/Alg-SIM hydrogel exhibited controlled pro-inflammatory responses (decreased 2.5- and 1.6-times IL-6 and TNF-α, respectively) and improved secretion of anti-inflammatory cytokines (increased 1.5- and 1.3-times IL-10 and TGF-β, respectively) in comparison with CMC/Alg. Furthermore, the CMC/Alg-SIM hydrogel facilitated rapid wound healing in the rat model with a full-thickness skin defect. After 14 days post-surgery, the wound healing ratio in the CMC/Alg hydrogel group (∼93%) was significantly greater than the control group (∼58%). Therefore, the engineered CMC/Alg-SIM hydrogel with desired immunomodulatory properties possesses the potential to enhance and accelerate skin regeneration for the management of chronic wound healing.

Porous and Dense Alginate/Chitosan Composite Films Loaded with Simvastatin for Dressing Applications

Alginate is a biocompatible polysaccharide matrix used for bioactive dressings with inherent healing properties. Most alginate dressings are produced as single-layer dressings. This study explores the potential of bilayer membranes to modulate drug release and enhance antimicrobial properties. We used alginate and chitosan loaded with simvastatin, an anti-inflammatory drug. One membrane comprised dense layers of both alginate and chitosan, while the other featured a dense alginate upper layer and a porous chitosan lower layer. The current study introduces a new approach in which a bilayer membrane is modeled instead of creating a polymeric blend between alginate and chitosan. The upper layer of the membrane contains only alginate loaded with simvastatin, while the bottom layer contains only chitosan. Another innovation is the study of the use of a porous lower layer of chitosan. Therefore, the association of these polymers in a bilayer and porous membrane gives advanced therapeutic dressings (with anti-inflammatory and antimicrobial properties intrinsic to the membrane) that are more efficient in the healing of complex wounds. Comprehensive characterization encompassed physicochemical, thermal, morphological, and mechanical properties. Microbiological tests were conducted using chitosan extract, and cytotoxicity evaluations were performed on fibroblast and keratinocyte cells. The results showed interlayer adhesion due to ionic interactions between alginate and chitosan surfaces. The drying process influenced the morphological and physicochemical features of the membranes. Simvastatin release profiles demonstrated sustained release over an extended period (approximately 60%–70% of the drug after 96 h). Storage assessments revealed that after six months, the membranes maintained around 98% of the initial simvastatin content. The antimicrobial activity test underscored the bacteriostatic efficacy of the chitosan porous layer, making it well-suited for infected wounds. Cell viability tests confirmed the non-cytotoxic nature of the films, highlighting their promising characteristics for treating diverse skin lesion types.

Preformulation Studies of Ezetimibe-Simvastatin Solid Dispersions in the Development of Fixed-Dose Combinations.

Two active pharmaceutical ingredients (APIs) with limited solubility, simvastatin and ezetimibe, prepared as a drug-drug solid dispersion (SD) was evaluated for physicochemical, microstructural, and aqueous dissolution properties. The simvastatin-ezetimibe SD was prepared using the co-grinding method in a wide range of weight fractions and differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) were used to perform the phase composition analysis. DSC studies confirmed that simvastatin and ezetimibe form a simple eutectic phase equilibrium diagram. Analysis of Fourier transform infrared spectroscopy (FTIR) studies excluded strong interactions between the APIs. Our investigations have revealed that all studied dispersions are characterized by substantially improved ezetimibe dissolution regardless of simvastatin content, and are best when the composition oscillates near the eutectic point. Data obtained in our studies provide an opportunity for the development of well-formulated, ezetimibe-simvastatin fixed-dose combinations (for hypercholesterolemia treatment) with reduced ezetimibe dosages based on its dissolution improvement.

Preparation of Solid Dispersions of Simvastatin and Soluplus Using a Single-Step Organic Solvent-Free Supercritical Fluid Process for the Drug Solubility and Dissolution Rate Enhancement.

The study was designed to investigate the feasibility of supercritical carbon dioxide (scCO2) processing for the preparation of simvastatin (SIM) solid dispersions (SDs) in Soluplus® (SOL) at temperatures below polymer’s glass transition. The SIM content in the SDs experimental design was kept at 10, 20 and 30% to study the effect of the drug–polymer ratio on the successful preparation of SDs. The SIM–SOL formulations, physical mixtures (PMs) and SDs were evaluated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and dissolution studies. The scCO2 processing conditions and drug–polymer ratio were found to influence the physicochemical properties of the drug in formulated SDs. SIM is a highly crystalline drug; however, physicochemical characterisation carried out by SEM, DSC, and XRD demonstrated the presence of SIM in amorphous nature within the SDs. The SIM–SOL SDs showed enhanced drug dissolution rates, with 100% being released within 45 min. Moreover, the drug dissolution from SDs was faster and higher in comparison to PMs. In conclusion, this study shows that SIM–SOL dispersions can be successfully prepared using a solvent-free supercritical fluid process to enhance dissolution rate of the drug.

Particle properties and drug metastable solubility of simvastatin containing PVP matrix particles prepared by electrospraying technique

In this work the preparation of drug loaded polymeric nanoparticles using electrospraying method and their subsequent characterization is presented. Our purpose was to incorporate the drug with extremely low solubility and low oxidative stability into polyvinylpyrolidone nanoparticles in order to improve its solubility and preserve its chemical stability and hence evaluate the ability of the technology to stabilize such systems in nanoparticulate form. Through the initial screening and optimization of process parameters and polymer solution properties, we detected different morphologies of electrosprayed product particles, where the use of lower molecular weight polymer resulted in a higher process instability as well as in a broader particle size distribution. On the other hand, the solution containing polyvinylpyrolidone with higher molecular weight showed sensitivity to different flow rates and electric field changes, which again resulted in differing the particle size and morphology. The electrosprayed products, prepared by sufficient process stability and having adequately narrow size distribution span, showed lower initial simvastatin contents than theoretically expected, which indicated an oxidative drug degradation already during the electrospraying process. The addition of antioxidants improved simvastatin chemical stability in the particles, during the process itself as well as after accelerated stability study. With an addition of butylated hydroxyanisole antioxidant mixture into initial polymer solution more than 95% of the drug content was preserved after one month at accelerated conditions, whereas in formulations without antioxidants simvastatin content was less than 6%. Antioxidants addition however did not influence only simvastatin stability but also simvastatin solubility. Surprisingly, antioxidants addition did decrease drug solubility in buffers (pH=4 and pH=6.8) for more than a half without any solid state changes of simvastatin. Potential hydrophobic interaction between simvastatin and antioxidants are hindering the drug solubility in the respective buffer, despite drug being in amorphous state.

New Validated Analytical Method for Determination of Simvastatin in Tablet Formulations by RP–HPLC

RP–HPLC method has been developed and validated for the determination of simvastatin (SVS) in pure form and in tablets. Fluvastatin sodium was used as internal standard. The determination was performed on Nucleodur column C8 (250×4.6 mm i.d., 5 µm particle size); the mobile phase consisted of a mixture of phosphate buffer solution (KH2PO4 0.05 M, pH 4.83) and methanol (20:80, v/v), pumped at a flow rate 1.0 mL min−1 . Analyte was monitored by UV detection at 230 nm. The mean retention times for fluvastatin and simvastatin were about 4.40 and 9.00 min, respectively. The method was proved linear in the range of 3.5– 550.0 µg mL-1 and exhibited good correlation coefficient (r>0.9998) and excellent mean recovery (100.71– 102.18%). Very good limit of detection of 0.63 µg mL-1 was found for SVS. The method was validated statistically and by recovery studies for linearity, precision, repeatability, and reproducibility. This method was successfully applied to the determination of simvastatin content in four marketed brands from Syria. A good agreement between this method with the pharmacopoeial method for the determination of simvastatin in some real samples demonstrates that the proposed method is suitable to quantify simvastatin in pharmaceutical formulations.

Quality evaluation of simvastatin compounded capsules

Simvastatin is commercially available as tablets and compounded capsules in Brazil. Very few reports regarding these capsules' quality, and consequently their efficacy, are available. The pharmaceutical quality of 30 batches of 20 mg simvastatin capsules from the market was evaluated by weight determination, content uniformity, disintegration (Brazilian Pharmacopeia), assay and dissolution test (USP32 tablet monograph). A HPLC method was developed for assay, content uniformity and dissolution test, and specifications were also established. Out of the 30 batches evaluated, 29 showed capsule disintegration within 45 min and individual weight variation was within ±10% or ±7.5% relative to average weight, for < or > 300 mg, respectively. Only 27 batches met dissolution test criteria with values >80% of the labeled amount in 45 min; 21 batches showed simvastatin content between 90.0-110.0% of the labeled amount and 19 batches had at least 9 out of 10 capsules with content uniformity values between 85.0-115.0% of the labeled amount with RSD<6.0%. Only 14 of all (30) batches fully met pharmacopeial quality standards. The establishment of test conditions and specification parameters for simvastatin capsules showed that there are relevant pharmacopeial quality differences between batches compounded by different pharmacies. For 53.33% of the tested products hypercholesterolemic treatment efficacy may be compromised.

Sensitive spectrophotometric assay of simvastatin in pharmaceuticals using permanganate

Two simple, sensitive, selective and inexpensive spectrophotometric methods are described for the determination of simvastatin (SMT) in bulk drug and in tablets using permanganate as the oxidimetric reagent. In method A, SMT is treated with a measured excess of permanganate in acetic acid medium and the unreacted oxidant is measured at 550 nm, whereas in method B the reaction is carried out in alkaline medium and the resulting manganate is measured at 610 nm. In method A, the amount of permanganate reacted corresponds to the SMT content and the absorbance is found to decrease linearly with the concentration; and in method B, the absorbance increases with concentration. The working conditions of assays were optimized, and the methods were validated according to the current ICH guidelines. Under optimum conditions, SMT could be assayed in the concentration ranges, 1.47 - 17.67x10-5 and 2.27 - 27.18 x10-6 mol/L by method A and method B, respectively. The calculated molar absorptivities are 3.2 x 10³ and 2.5 x 10(4) L/mol/cm for method A and method B, respectively with corresponding Sandell sensitivity values of 0.0387 and 0.0178 μg/cm². The limits of detection (LOD) and quantification (LOQ) have also been reported. Accuracy and precision for the assay were determined by calculating the intra-day and inter-day at three concentrations; the intra-day RSD was < 2% and the accuracy was better than 2.15 % (RE). The methods were applied successfully for the determination of SMT in tablet dosage form with a high percentage of recovery, good accuracy and precision, and without measurable interference by the excipients. The accuracy was further ascertained from placebo and synthetic mixture analysis and also from the spike-recovery method.

Bromatometric assay of simvastatin in pharmaceuticals

Titrimetric and spectrophotometric methods are proposed for the determination of simvastatin (SMT) in bulk drug and in tablets. The methods employ bromate-bromide mixture in acid medium as the brominating agent and iron (III) and thiocyanate as auxiliary regents. In titrimetry, SMT is treated with a measured excess of bromate-bromide mixture in HCl medium, and after a definite time, the unreacted bromine is determined iodometrically. In spectrophotometric method, the residual bromine is reduced by iron (II) and the resulting iron (III) is complexed with thiocyanate, and the absorbance is measured at 470 nm. In both methods, the amount of in situ generated bromine corresponds to the SMT content. The experimental conditions are optimized. Titrimetry is applicable over 1–10 mg range and the calculations are based on the molar ratio of 1: 0.666 (SMT: KBrO3). In spectrophotometric method, Beer’s law is obeyed over the concentration range 1–10 µg/mL. The calculated molar absorptivity is 3.02 × 104 L/mol cm and the corresponding sandel sensitivity being 0.0081 µg/cm2. The limit of detection (LOD) and limit of quantification (LOQ) are calculated to be 0.10 and 0.31 µg/mL, respectively. The intra-day and inter-day precision calculated from the analysis of pure SMT were less than 2 and 2.7%, respectively. The methods were satisfactorily applied to the determination of SMT in tablets, and no interferences from common tablet excipients were observed. The validity of the methods was further ascertained by parallel assay by an established technique and by recovery studies.