Dissolution Rate Of Simvastatin Research Articles

Formulation for Enhancement of Solubility and Dissolution Rate of Simvastatin using Solid Dispersion

Solid dispersion preliminary solubility analysis was carried out for the selection of the carrier and solid dispersion was prepared with Hydroxy Propyl Methyl Cellulose (HPMC) and Methyl Cellulose (MC). These solid dispersions were analyzed for the solubility and in-vitro dissolution profile solid dispersion of drug with polymer has shown enhanced solubility with improved dissolution rate. Further FTIR, X-Ray studies were carried out. The solubility and dissolution rate of Simvastatin, a drug used for the treatment of hyperlipidaemia. Simvastatin is a selective competitive inhibitor of HMG Co-A reductase. However its absolute bioavailability is 5%. To increase the solubility of drug solid dispersion was prepared. Solid dispersion prepared with polymer in 1:5 ratios shows the presence of amorphous form confirmed by the characterization study. The present investigations showed that solubility of Simvastatin Sodium was markedly increased by its solid dispersion using PVP K30 as carrier. The formulation SDF8 containing (1:8) shows highest dissolution rate. Hence the solid dispersion a way is useful technique in providing fastest onset of action of Simvastatin Sodium as well as enhanced dissolution rate. The study also shows that dissolution rate of Simvastatin can be enhanced to considerable extent by solid dispersion technique with Polymer.

Improvement of Solubility and Dissolution Rate of Simvastatin by Solid Dispersion Technique

The aim of present work is to enhance the solubility and bioavailability of Simvastatin by solid dispersion technique and characterize the same. Preliminary solubility studies were conducted to check the solubility in different polymers. Based on the results 20 formulations prepared by solvent evaporation method with varying ratios of Kleptose HPB, Soluplus, Kolliwax GMS II, Kolliphor P188 and PVPK-30. All the formulations were analyzed for solubility, percentage yield, drug content and in vitro drug release. The formulation SD20 with enhanced solubility of 20.05 ± 0.02μg/mL in Kolliwax GMS II, percentage yield of 99.13% and dissolution rate of 99.2 ± 2.3% within 90 min is chosen as optimized formulation. The formulation is further Characterized for Drug excipient interaction by FTIR, PXRD and SEM studies. The stability studies for 6 months indicated no significant changes in drug content or drug dissolution rate. Hence, improve dissolution characteristics of Simvastatin achieved by increasing its release and solubility through solid dispersion technique.

Synergistic effect of polyethylene glycol and superdisintegrant on dissolution rate enhancement of simvastatin in pellet formulation

Slow dissolution is a major drawback for poorly water-soluble drugs when they are extruded-spheronized with microcrystalline cellulose (MCC). Therefore, the aim of the current study was to explore excipients to enhance the dissolution of simvastatin without compromising the extrudability and sphericity of pellets. Pellets containing simvastatin, MCC and polyethylene glycols (PEGs) or superdisintegrants were prepared by extrusion-spheronization and their micromeritics and mechanical properties, drug release and solid state of simvastatin were studied. All formulations produced pellets with reasonable size and sphericity. Generally, the inclusion of PEG and superdisintegrants decreased crushing strength and elastic modulus of pellets and increased the dissolution rate of simvastatin. A substantial increase in dissolution rate was observed when a combination of PEG and superdisintegrant was used due to the formation of more porous matrix, faster disintegration and remarkable reduction in drug crystallinity. It was interesting to note that the use of PEG and superdisintegrant had a synergistic effect on the dissolution enhancement of simvastatin in pellet formulation. The results of this study confirmed that a simple method of extrusion-spheronization can be employed to enhance the dissolution of simvastatin in multi particulates dosage form which can also be employed for other poorly water-soluble drugs.

FORMULATION, OPTIMIZATION, AND EVALUATION OF SITAGLIPTIN AND SIMVASTATIN RAPIDLY DISSOLVING TABLETS

Objective: The scope of this work was to formulate sitagliptin and simvastatin rapidly dissolving tablets. However, simvastatin is practically insoluble in water. For improving its poor oral bioavailability and with the aim of facilitating administration to patients facing problems with swallowing rapidly dissolving tablets were preparedMethods: Tablets were prepared using superdisintegrant addition technique using croscarmellose sodium (Ac-di-sol), sodium starch glycolate (explotab) and crospovidone in different percentages. Evaluation tests such as weight variation, thickness, and content variation, and friability, disintegration, wetting time, in vitro dispersion and in vitro dissolution were carried out.Results: The results showed that the presence of crospovidone could enhance the dissolution rate of simvastatin greatly. The best-optimized formulae found were that F8, F9, and F10 which showed good disintegration and the dissolution rate of simvastatin and sitagliptin was more than 90% after 10 min while the dissolution rate for simvastatin and sitagliptin pure standards was 12% and 30%, respectively after 10 min.Conclusion: Some tablet formulae showed acceptable pharmacotechnical properties and complied with compendium requirements. Results of dissolution studies revealed that F8-F10 showed an increase in the dissolved sitagliptin and simvastatin to be more than 90% after 10 min.

ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF SIMVASTATIN BY USING SOLID DISPERSION TECHNIQUE ALONG WITH DIFFERENT COMBINATION OF POLYMERS

The solubility and dissolution rate of simvastatin, a drug used for the treatment of hyperlipidaemia. Simvastatin is a selective competitive inhibitor of HMG Co A reductase. However its absolute bioavailability is 5%. To increase the solubility of drug solid dispersion was prepared. Solid dispersion preliminary solubility analysis was carried out for the selection of the carrier and solid dispersion was prepared with Hydroxy Propyl Methyl Cellulose (HPMC) and Methyl Cellulose (MC). These solid dispersions were analyzed for the solubility and in-vitro dissolution profile solid dispersion of drug with polymer has shown enhanced solubility with improved dissolution rate. Further FTIR, X-Ray studies were carried out. Solid dispersion prepared with polymer in 1:5 ratios shows the presence of amorphous form confirmed by the characterization study. The study also shows that dissolution rate of simvastatin can be enhanced to considerable extent by solid dispersion technique with Polymer. Keywords: Solubility enhancement, Solid dispersion, Low aqueous solubility

Co-crystallization: A Tool to Enhance Solubility and Dissolution Rate of Simvastatin

Objective : The aim of this study was to explore co-crystallization to enhance the solubility of simvastatin (SV) as a drug of choice for hypercholesterolemia using saccharin (Sacch) as co-former. Methods: Molecular modeling of sacch against SV has been conducted by in silico using auto dock 4.2. Preparation of co-crystal has carried out by solvent evaporation (SE) using an equimolar ratio of SV and Sacch. Co-crystal of SV- Sacch was evaluated by the saturated solubility test and intrinsic dissolution test. Afterward, the co-crystal was characterized by infrared spectrophotometry (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), binary phase diagram and stability studies in storage condition 400C and relative humidity (RH) 75% for three months. Results: In silico studies showed that the interaction of SV against sacch has hydrogen bonding as molecular synthon. Evaluations of solubility and intrinsic dissolution have shown an increased in rate properties significantly of co-crystal as compared to pure SV and its physical mixer (PM). Characterizations of a co-crystal SV: sacch (1: 1) has indicated the formation of different new solid crystal phase as compared to SV, sacch, and its PM, and stable for 400C and RH 75% in 3 months. Conclusion: Co-crystallization has been used to increase the solubility and dissolution rate of simvastatin and all characterization has shown the formation of co-crystal SV: sacch (1: 1). Key words: Co-crystal, Simvastatin, Saccharin, Solubility, Dissolution.

Formulation aspects of Solid Dispersions of Simvastatin

The aim of the present work was to improve dissolution rate of Simvastatin, a drug used for the treatment of hyperlipidemia. Simvastatin is a selective competitive inhibitor of HMG CoA reductase. However its absolute bioavailability is 5 % hence to increase it further solid dispersions were prepared. Solid dispersions were prepared with PVP-K30 at different drug: polymer ratios. These solid dispersions were analyzed for in-vitro dissolution profile, and solid dispersions of drug with PVP-K30 at all drug: polymer ratios had shown improved dissolution rate. FTIR studies showed no interactions among drug and polymers. The study shows that the dissolution rate of Simvastatin can be enhanced to considerable extent by solid dispersion technique with PVP-K30. From the above study it can be concluded that solid dispersion of Simvastatin improved the drug dissolution profile. It was found that by varying the drug polymer ratio and by using different methods of preparation of solid dispersion, the dissolution rate of pure drug can be enhanced. The present work concluded that solid dispersion technology can be used successfully to enhance the dissolution rate of poorly soluble drugs.

Formulation and Evaluation of Nanosuspension of Simvastatin

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.

Influence of process variables on the properties of simvastatin self-emulsifying granules obtained through high shear wet granulation

Improvements of the oral bioavailability of lipophilic drugs can be obtained using lipidic formulations such as the self-emulsifying drug delivery systems. The high shear wet granulation (HSWG), using microemulsions as binder, is a viable process to produce self-emulsifying granules. However only few information are present in the literature on the effect of process variables on the properties of the granules obtained with these binders. Consequently, this article compares the effects of some relevant experimental variables (impeller speed and massing time) on the final technological and pharmaceutical properties of the granules produced using simple water, or alternatively, a microemulsion as binder and containing simvastatin (SV) as model drug. The effects of the variables were determined by evaluating the granule median diameter, their particle size distribution, roundness, disintegration time and dissolution rate of SV. Results clearly demonstrated that the microemulsion-based process was less sensitive to operating conditions than the water-based process. With microemulsion the nucleation process and growth regimes were more difficult to control, resulting in products with broader PSDs. At the same operating conditions microemulsion-based granules were more brittle but rounder and showed smaller median diameter compared to water-based granules. The dissolution rate of simvastatin was not significantly affected by the operating conditions.

Formulation and Evaluation of Nanosuspension Formulation for Drug Delivery of Simvastatin

Poor water solubility and slow dissolution rate are issues drug content and polydispersity index. The obtained for the majority of upcoming and existing biologically results showed that particle size (nm) and rate of active compounds. Simvastatin is poorly water-soluble dissolution has been improved when nanosuspension drug and its bioavailability is very low from its crystalline prepared with the higher concentration of PVPK-30 and form. The purpose of the present investigation was to Poloxamer-188 and lower concentration of SLS. The increase the solubility and dissolution rate of simvastatin by particle size and zeta potential of optimized formulation the preparation of nanosuspension by Emulsification was found to be 258.3 nm and 23.43. The rate of Solvent Diffusion Method at laboratory scale. Prepared dissolution of the optimized nanosuspension was nanosuspension was evaluated for its particle size and enhanced (90.02% in 60min), relative to plain simvastatin in vitro dissolution study and characterized by zeta (21% in 60 min), mainly due to the formation of nanosized potential, differential scanning calorimetry (DSC) and particles. These results indicate the suitability of 23 factorial X-Ray diffractometry (XRD), Motic digital microscopy, design for preparation of simvastatin loaded nanosus- entrapment efficiency, total drug content, saturated pension significantly improved in vitro dissolution rate, solubility study and in vivo study. A 23 factorial design was and thus possibly enhance fast onset of therapeutic drug employed to study the effect of independent variables, effect. In vivo study shows increase in bioavailability in amount of SLS (X1), amount of PVPK-30 (X2) and nanosuspension formulation than the plain simvastatin Poloxamer-188 (X3) and dependent variables are Total drug.

Synthesis of novel core-shell structured dual-mesoporous silica nanospheres and their application for enhancing the dissolution rate of poorly water-soluble drugs

Novel core-shell dual-mesoporous silica nanospheres (DMSS) with a tunable pore size were synthesized successfully using a styrene monomer as a channel template for the core and cetyltrimethyl ammonium bromide (CTAB) as a channel template for the shell in order to improve the dissolution rate of poorly water-soluble drugs. Simvastatin was used as a model drug and loaded into DMSS and the mesoporous core without the shell (MSC) by the solvent evaporation method. The drug loading efficiency of DMSS and MSC were determined by thermogravimetric analysis (TGA) and ultraviolet spectroscopy (UV). Characterization, using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR) showed that simvastatin adsorbed in DMSS and MSC was in an amorphous state, and in vitro release test results demonstrated that both DMSS and MSC increased the water solubility and dissolution rate of simvastatin. The shell structure of DMSS was able to regulate the release of simvastatin compared with MSC. It is worth noting that DMSS has significant potential as a carrier for improving the dissolution of poorly water-soluble drugs and reducing the rapid release.

Formulation and Evaluation of Nanosuspension Delivery System for Simvastatin

Poor water solubility and slow dissolution rate are issues polydispersity index. The obtained results showed that for the majority of upcoming and existing biologically active 
 particlesize (nm) and rate of dissolution has been improved compounds. Simvastatin is poorly water-soluble drug and when nanosuspension prepared with the higher its bioavailability is very low from its crystalline form. The concentration of PVPK-30 with the higher concentration of purpose of the present investigation was to increase the 
 PVP K-30 and Poloxamer-188 and lower concentration of solubility and dissolution rate of simvastatin by the SLS. The partical size and zeta potential of optimized preparation of nanosuspension by Emulsification Solvent formulation was found to be 258.3 nm and 23.43. The rate Diffusion Method at laboratory scale. Prepared nanosus- of dissolution of the optimized nanosuspension was pension was evaluated for its particle size and in vitro enhanced (90.02% in 60 min), relative to plain simvastatin dissolution study and characterized by zeta potential, (21% in 60 min), mainly due to the formation of nanosized differential scanning calorimetry (DSC) and X-Ray particles. These results indicate the suitability of 23 factorial diffractometry (XRD), motic digital microscopy, entrapment design for preparation of simvastatin loaded efficiency, total drug content, saturated solubility study and nanosuspension significantly improved in vitro dissolution in vivo study. A 23 factorial design was employed to study rate, and thus possibly enhance fast onset of therapeutic the effect of independent variables, amount of SLS (X1), drug effect. In vivo study shows increase in bioavailability in amount of PVPK-30 (X2) and Poloxamer-188 (X3) and nanosuspension formulation than the plain simvastatin dependent variables are total drug content and drug.

Formulation and Optimization of Nanosuspensions for Enhancing Simvastatin Dissolution Using Central Composite Design

Simvastatin is a poorly water-soluble drug, and bioavailability from its crystalline form is very low. The purpose of this investigation was to increase the solubility and dissolution rate of simvastatin by the preparation of nanosuspensions with Pluronic F127 and zirconium oxide (ZrO2) beads using a wet-milling technique at the laboratory scale. Prepared nanosuspensions were evaluated for particle size and in vitro dissolution. A 3 2 central composite design was employed to study the effect of the independent variables (i.e., amount of Pluronic F127, X1, and amount of ZrO2, X2) on the dependent variables (i.e., particle size [nm] and percentage of drug released after 10 min, Q10). The relationship between the dependent and independent variables was further elucidated using multiple liner regression analysis (MLRA) and contour plots. The results show that nanosuspensions prepared with the higher concentrations of Pluronic F127 and the higher quantities of ZrO2 (up to 8 g) reduced the particle size and enhanced the dissolution rate of the formulation. The dissolution rate of the optimized nanosuspension was enhanced (64% in 10 min) relative to that of a micronized suspension of simvastatin (3.5% in 10 min), mainly because of the formation of nanosized particles. These results show that the preparation of simvastatin-loaded nanosuspensions significantly improved the in vitro dissolution rate, thus possibly enhancing the fast onset of therapeutic drug effect.

Preparation, Characterization, and Dissolution Behavior of a Solid Dispersion of Simvastatin with Polyethylene Glycol 4000 and Polyvinylpyrrolidone K30

The aim of the present study was to improve the solubility and dissolution rate of a poorly water‐soluble drug, Simvastatin, by a solid dispersion technique. Solid dispersions were prepared with polyethylene glycol 4000 (PEG 4000) by fusion‐cooling and solvent evaporation techniques whereas with polyvinylpyrrolidone K30 (PVP K30) by solvent evaporation technique in different drug‐to‐carrier ratios. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, x‐ray powder diffraction, and FTIR spectroscopy. The aqueous solubility of Simvastatin was favored by the presence of both polymers. Solid state characterization indicated Simvastatin was present as amorphous material and entrapped in polymer matrix. Solid dispersion prepared with PVP showed highest improvement in wettability and dissolution rate of Simvastatin. Tablets containing solid dispersion prepared with PEG and PVP showed significant improvement in the release profile of Simvastatin as compared to tablet containing Simvastatin without PEG or PVP.