Formulation, in vitro evaluation and characterization of atorvastatin solid dispersion (original) (raw)
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Egyptian Pharmaceutical Journal, 2023
The goal of this study was to evaluate different proportions of solid dispersions and formulations by employing various carriers in order to improve solubility of poorly soluble atorvastatin calcium. Materials and methods Solid dispersions can be created using the Solvent Evaporation technique. In comparison to pure drug, (Hydroxy propyl methyl cellulose) HPMC (1:1) indicated as (Solid dispersion) SD1, HPMC E5 (1:2), HPMC E5 (1:4), HPMC (1:1.5) designated as SD2, SD3, SD4, drug caffeine (1:0.5) and caffeine (1:1), denoted as SD5, SD6. The Design Expert software used to 2 level factorial design, the three independent components of X1: are ratios of solid dispersion equivalent (drug: HPMC:soluplus), X2:Superdisintegrant (Primellose), and X3:Surfactant (Sodium lauryl sulphate) was used to do analysis of variance (ANOVA), 3D surface plots, counter plots, optimization, and desirability. Fourier-transform infrared spectroscopy was used to investigate drug-excipient compatibility. Marketed tablets (uncoated tablets manufactured by 'Revat Laboratories limited) with optimized tablet composition were used in the comparative trials (A2) and Pharmacokinetics. Results and discussion The solid dispersion approach greatly increased the amount of atorvastatin calcium released. The values of f1 and f2 were determined to be 1.89 and 77.78, respectively, and the dissolution profiles of the optimized formulation (A2) and the market tablet were found to be significance. The optimized formula did better on the desirability level (0.975), indicating that it was a good fit. To determine dose bioavailability and to see if there is an in-vitro-in-vivo link. Conclusion The formulations were successfully developed using factorial design, and can be further used for oral delivery of antilipidemic agents is atorvastatin calcium. The model's predictability and validity were demonstrated when the experimental values matched the expected values. The in vitro-in vivo correlation was good in pharmacokinetic experiments, indicating a significant improvement.
Formulation and evaluation studies of Atorvastatin calcium sustained release tablet
Atorvastatin calcium is a poorly water soluble compound marketed in Bangladesh under bio-waiver conditions. The present study aimed to develop formulation and drug excipients compatibility study of Atorvastatin calcium (50 mg) sustain release tablet and optimize the final formula. The tablets were formulated by direct compression method and the results obtained were extrapolated. Solid dispersion of Atorvastatin calcium was prepared by using Hydroxypropyl methyl cellulose, Methyl cellulose, Lactose, Guar gum, Xanthan gum & Magnesium Stearate .The in vitro equivalence test was carried out in three different media. Test results were subjected to statistical analysis to compare the dissolution profiles. Other general quality parameters of these tablets such as weight variation, friability, thickness, hardness and disintegration time were also determined according to established protocols. Final formulation of solid dispersed Atorvastatin calcium revealed that successfully improvement of solubility as well as dissolution of Atorvastatin calcium in long time. This study could be very much helpful for better bioavailability of poorly water soluble drug avoiding first pass metabolism. Finally, we can claim that prepared tablets are proved to be promising dosage form for sustained drug delivery of Atorvastatin calcium by reducing dosing frequency and increasing the patient compliance.
Enhancement of dissolution rate of atorvastatin calcium using solid dispersions by dropping method
The objective of the present investigation was to study the effect of polyethylene glycol 4000 (PEG 4000) and polyethylene glycol 6000 (PEG 6000) on in vitro dissolution of Atorvastatin Calcium (ATC) from solid dispersions. Initial studies were carried out using physical mixtures of the drug and carrier. Solid dispersions were prepared by the dropping method. Atorvastatin was formulated as physical mixtures and solid dispersions (dropping method) using 1:1, 1:2 and 1:3 ratios of drug and carriers (PEG 4000 & PEG 6000). Saturation solubility study for pure drug, physical mixtures and solid dispersions were carried out in water and pH 6.8 phosphate buffer solutions (PBS). The In vitro dissolution studies were carried in pH 6.8, higher in vitro dissolution of solid dispersions was recorded compared to their corresponding physical mixtures and the pure drug. The prepared solid dispersions showed marked increase in the saturation solubility and dissolution rate of Atorvastatin than that of pure drug. PEG 6000 in 1: 3 drug to carrier ratio exhibited the highest drug release (89.65%) followed by PEG 4000 (80.03%) in the same ratio formulated as solid dispersions using dropping method. The FT-IR shows the complexation and there were no interactions. Finally solid dispersion of Atorvastatin: PEG 6000 prepared as 1:3 ratio by dropping method showed excellent physicochemical characteristics and was found to be described by dissolution release kinetics and was selected as the best formulation.
2016
E-mail: sanju1980dey@gmail.com The objective of the present study was to prepare solid dispersion (SD) and inclusion complexes of atorvastatin (ATV) using different hydrophilic carriers (polyethylene glycol (PEG 4000 and PEG 6000), polyvinyl pyrrolidone (PVP K30), and D-mannitol) and β-cyclodextrin (β-CD), respectively to improve the aqueous solubility and dissolution rate. Different drug: carrier ratios (1:1, 1:2, and 1:3) were used and their effects on the dissolution performance were studied. The physical state and drug-carrier interaction in solid state were analyzed by infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. The dissolution rate of ATV from tablets containing β-CD inclusion complex was compared with conventional tablets without β-CD. In vivo pharmacokinetic studies were performed on rabbits to compare the in vivo performance between tablets with or without inclusion complex. Improvement in the drug dissolution rate was observed in SDs an...
Acta Pharmaceutica Sinica B, 2012
Atorvastatin has low aqueous solubility resulting in low oral bioavailability (12%) and thus presents a challenge in formulating a suitable dosage form. To improve the aqueous solubility, a solid dispersion formulation of atorvastatin was prepared by lyophilization utilising skimmed milk as a carrier. Six different formulations were prepared with varying ratios of drug and carrier and the corresponding physical mixtures were also prepared. The formation of a solid dispersion formulation was confirmed by differential scanning calorimetry and X-ray diffraction studies. The optimum drugto-carrier ratio of 1:9 enhanced solubility nearly 33-fold as compared to pure drug. In vitro drug release studies exhibited a cumulative release of 83.69% as compared to 22.7% for the pure drug. Additionally, scanning electron microscopy studies suggested the conversion of crystalline atorvastatin to an amorphous form. In a Triton-induced hyperlipidemia model, a 3-fold increase in the lipid lowering potential was obtained with the reformulated drug as compared to pure drug. These results suggest that solid dispersion of atorvastatin using skimmed milk as carrier is a promising approach for oral delivery of atorvastatin.
Formulation development and in vitro evaluation of nanosuspensions loaded with Atorvastatin calcium
Asian Journal of Pharmaceutics, 2010
The purpose of this investigation is to develop extended release matrix tablets of propranolol hydrochloride (PPH), which were designed to improve the patient compliance and prolong the drug release after oral administration. Different viscosity grades of hydroxypropyl methylcellulose (HPMC) polymers such as HPMC K4 M, HPMC K15 M and HPMC K100 M were used. The prepared formulations were characterized and all formulations exhibited satisfactory physical parameters such as thickness (mm), weight variation (mg), friability (%) and hardness (kg/cm 2). After evaluation of physical properties, the in vitro release study was performed in 0.1 N Hydrochloric Acid (HCl), pH 1.2 for 2 hours followed by release in phosphate buffer pH 6.8 up to 12 hours. The effects of polymer concentration and polymer blend concentration were studied. Among all the formulations, formulation F3 which contains 40% HPMC K4M followed zero order kinetics via, swelling, diffusion and erosion. This study gives the preliminary idea about the development of extended release drug delivery systems of PPH. The in-vitro drug release exponent of the peppas equation suggests the drug release mechanism was super case II transport mechanism. Based on compatibility studies such as differential scanning calorimetry (DSC) and fourier transform infrared spectrophotometry (FT-IR), there was no interaction between the drug and excipients.
In vitro dissolution study of atorvastatin binary solid dispersion
Journal of Advanced Pharmaceutical Technology & Research, 2013
The aim of the present study was to improve the solubility and dissolution rate of atorvastatin (ATV), a slight water-soluble drug, by solid dispersion (SD) technique using a hydrophilic carrier Poloxamer 188 (POL188). Physical mixing (PM) and solvent evaporation (SE) method were used to prepare ATV-SD where different drug-carrier ratios were used. Prepared formulations were characterized in their solid state by solubility study; differential scanning calorimetry, scanning electron microscopy, and Fourier transform infrared spectroscopy which demonstrated changes in the formulations supporting the improved solubility. Percent content of POL188 in the SD matrix was found to play the pivotal role in the improvement of dissolution property of ATV. In case of PM, highest enhancement in drug release was found for 1:3 ratio (P < 0.05, ANOVA Single factor) whereas in case of SE, 3:0.5 ratio of ATV-POL188 resulted the maximum enhancement in ATV release (P < 0.05, ANOVA Single factor). Analysis of dissolution data of optimized formula indicated the best fitting with Peppas-Korsmeyer model and the drug release kinetics was fickian diffusion. In conclusion, binary SD prepared by both PM and SE technique using POL188 could be considered as a simple, efficient method to prepare ATV solid dispersions with significant improvement in the dissolution rate.
Approaches to Improve Atorvastatin Calcium Bioavailability : A Review H Review
2020
Poor bioavailability is one among major challenges faced by the pharmaceutical drugs in the dosage form development. Atorvastatin (AST) is one among such challenging drugs facing poor bioavailability due to poor solubility. The objective of this article is to review the literature published in the selected search engines about the solubility / bioavailability enhancement of AST. Literature was searched in the four databases Science direct, PubMed, Google scholar, and BASE engine. Seventy-one articles related to atorvastatin formulations were selected from which 26 articles related to bioavailability enhancement were discussed. Further, various method of estimation of AST alone and in formulations were also compiled. Results: researches that the bioavailability could be improved by several methods including solid-dispersion co-crystallization, Microspheres, solid lipid nanoparticles, co-solvency, and nanosuspension, self-nano emulsifying drug delivery system (SNEEDS). Further, simple...
BioMed Research International, 2014
The objective of this investigation was to improve the solubility of the poorly water soluble drug atorvastatin (ATR), using solid dispersion (SD) techniques, with Neem Gum (NG) as a hydrophilic carrier. The effects of the polymer concentration and method of preparation on the solubility and dissolution rate were studied. The results showed that the solubility of ATR increases with increasing NG concentration. However, dissolution rate of ATR from its SD was dependent on the method used to prepare SD. Anin vitrodrug release study revealed that the solvent evaporation technique is a more convenient and effective method of preparing SD than kneading method. The SD was characterized using DSC, SEM, and XRD study. Anin vivostudy was performed in which the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibition activity was measured. A significant reduction in HMG CoA reductase activity was observed with SD of ATR compared with the plain drug. Anex vivoabsorption study was ...
FORMULATION DEVELOPMENT AND EVALUATION OF FAST DISSOLVING ORAL FILM OF ATORVASTATIN CALCIUM
Fast dissolving oral films (FDOFs) are the most advanced form of oral solid dosage form due to more flexibility and comfort. It improve the efficacy of APIs by dissolving within minute in oral cavity after the contact with less saliva as compared to fast dissolving tablets, without chewing and no need of water for administration. Atorvastatin is a lipid lowering agent and widely used to treat hypercholestermia. However following oral administration, the bioavailability of the drug is only 12% due to extensive first pass metabolism. The aim of present work is to formulate and evaluate fast dissolving oral films of atorvastatin calcium to improve water solubility, dissolution rate, oral bioavailability and reduction of first pass metabolism and increase patient’s compliance. Oral fast dissolving films prepared by solvent casting method using water and 95% ethanol as solvents and HPMC as film forming polymer. PEG 400 was the selected plasticizers, Superdisintegrants such as croscarmellose sodium (CCS), crospovidone (CP) and sodium starch glycolate (SSG) alone and also in combinations was incorporated to achieve the aim. The prepared films were evaluated for the drug content, weight variation, film thickness and disintegration time, folding endurance, percentage of moisture content and in vitro dissolution studies and taste mask studies on healthy human volunteers. Among all, the formulation F4 was found to be best formulation which releases 98.95 % of the drug within 15 min and disintegration time is 168sec. which was significantly high when compared to other formulation. The results revealed that, atorvastatin fast dissolving oral films could be considered as promising drug delivery system for hyperlipidemic patients. Keywords: Atorvastatin, Hypercholestermia, Fast dissolving films, Solvent casting method, Superdisintegrants.