Formulation and Characterization of Gastroretentive Floating Tablets of Atorvastatin Calcium Using Central Composite Design (original) (raw)
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Preparation and Evaluation of Gastro Retentive Floating Tablets of Atorvastatin Calcium
This investigation describes the preparation and in vitro evaluation of gastro retentive floating tablets of atorvastatin calcium. Two hydrophilic cellulose derivatives, Methocel K4M and Methocel K15M CR were used in floating tablets as gel forming agents to control drug release. Sodium bicarbonate and citric acid were incorporated as gas generating agents. The tablets prepared by direct compression technique were evaluated by various quality parameters including weight variation, hardness and buoyancy studies. In vitro drug release was determined for eight hours using USP XXII paddle-type dissolution apparatus in 0.1N HCl solution containing 1% sodium lauryl sulphate. The release mechanisms were explored and explained with zero order, first order, Higuchi and Korsmeyer equations. The release rates, extent and mechanisms, were found to be governed by polymer loading. It was also found that the polymer content significantly affected the mean dissolution time, percentage of drug release, release rate constant and diffusion exponent. Based on the dissolution data and floating time, formulation F-3 containing Methocel K4M and F-9 containing Methocel K15M CR may be considered as the best formulation. So an effective floating tablet of atorvastatin calcium can be prepared by using both the grades of HPMC. INTRODUCTION Most of the orally administered dosage forms have several physiological limitations, such as GI transit time, impaired drug absorption due to incomplete release of drug from the dosage forms and too short residence time of the dosage forms in the absorption region of GI tract. Gastro-retentive systems can remain in the gastric region for several hours and hence can significantly prolong the gastric residence time of drugs. Prolonged gastro retention of the therapeutic moiety may offer numerous advantages: better bioavailability, reduced drug waste and improved solubility of drugs that are less soluble in a high pH environment of small intestine. 1 It can also be used for local drug delivery to the stomach and proximal small intestine.
ENHANCEMENT OF BIOAVAILABILITY OF ATORVASTATIN CALCIUM THROUGH GASTRIC RESIDENT FORMULATION APPROACH
Atorvastatin calcium (ATC), a lipid-lowering drug, is much less bioavailable because of insufficient time for absorption in the GI tract. The real issue in the development of oral drug delivery systems is to prolong the residence time of the dosage form in the stomach or upper GI tract until the drug is completely released and absorbed. Several approaches are currently used to retain the dosage form in the stomach. The principle of ATC floating tablets offers a simple and practical approach to achieve increased GRT to enhance the bioavailability and to obtain CR/SR. ATC Floating tablets are designed based on gas generating principle. Design of ATC floating tablets needs a strong matrix former. All the floating tablets prepared were evaluated for hardness, friability, floating characteristics, swelling index, in vitro drug release characteristics, stability and in vivo radiographic studies and were subjected to FTIR, DSC and p-XRD studies. Formulation TF15 obtained the desired drug release profile and floated with a lag time of 48 sec, for these reasons it was considered as the best formulation among all the formulations. Olibanum might be a promising polymer for Gastroretentive floating drug delivery systems in combination with synthetic hydrophilic polymer i.e., PEO enhanced the floating duration and help to maintain the dimensional stability at initial stage. The bioavailability studies were carried out for the optimized formulation and compared with that of reference formulation in twelve rabbits. Based on in vivo performance significant difference was observed between C max, tmax, t1/2, AUC0-∞ and MRT of TF15 and control formulation. The increased relative oral bioavailability (fr) of test formulation (TF15) was 1.94 folds when compared to control formulation. The increased relative oral bioavailability may be due to floating (Gastroretentive) of dosage form, which is desirable for the drugs absorbed in the upper part of GIT. The developed floating tablets of ATC may be used for prolonged drug release, thereby improving the bioavailability and patient compliance.
Formulation, Development and Evaluation of Floating Matrix Tablets of Atorvastatin Calcium
The present study was aimed to prepare a Floating Matrix drug delivery system for the Atorvastatin calcium, andevaluating the various processing parameters including the buoyancy studies and in vitro drug release studies. Fifteen formulations containing varying proportions of polymers like HPMC K100M, HPMC K15M, Ethyl Cellulose and Carbopol 934P and fixed amount of gasgenerating agent such as Sodium bi carbonate and Citric Acid and also MCC in varying concentration as a bulking agent. The tablets were prepared by direct compression technique and the prepared tablets remained buoyant for more than 12 hrs in therelease medium. Batch F15 prepared with different proportions of HPMC K4M, HPMC K100 M and Carbopol 934P showed significant difference in 105 secs, Floating lag time, Total floating time more than 18 hrs and 62.11% releaseupto 12 hrs of the drug which shows extended release may be more than 15 hrs. All theformulations exhibited diffusion dominant drug release. F15 batch also showed stable in means of % Drug Content as it shows no significant change performed as per ICH guidelines for 60 Days.
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.
LATIN AMERICAN JOURNAL OF PHARMACY
The objective of this study was to improve the availability of atorvastatin calcium (ATC) and evaluate the effect of formulation variables on the buoyancy lag time (BLT), total floating time (TFT), and the release properties, when developed as gastro retentive floating tablets by the statistical optimization technique based on the simplex lattice design. The tablets were prepared by direct compression technique and were evaluated for weight variation, content uniformity, hardness, friability, and floating property. The floating behavior and in vitro dissolution studies were carried out. It was noted that, all the prepared tablets had desired BLT and constantly floated on dissolution medium. The optimized formulation released approximately 75% drug in 12 h and followed the Higuchi release model, while the BLT was 2 s and the tablet remained floatable thoughout the test. The results demonstrate the feasibility of the model in the development of gastro retentive floating tablets containing ATC.
Formulation and Evaluation of Rosuvastatin Calcium Oral Floating Tablets
Research Journal of Pharmacy and Technology
The present study was aimed at preparing a Floating drug delivery system for the model drug Rosuvastatin calcium, and evaluating the various processing parameters including the buoyancy studies and in vitro drug release studies. Four formulations containing varying proportions of polymers like HPMC K4M and Ethyl cellulose and fixed amount of gas generating agent such as Sodium bi carbonate and hydrophobic meltable material like bees wax were prepared. The tablets were prepared by melt granulation technique and the prepared tablets remained buoyant for more than 8hrs in the release medium. The proportions of the polymers showed significant difference in the release of the drug. All the formulations exhibited diffusion dominant drug release and were found to be stable.
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, in vitro evaluation and characterization of atorvastatin solid dispersion
Tropical Journal of Pharmaceutical Research
Purpose: To formulate a polymer-incorporated solid dispersion preparation for enhancing the dissolution and bioavailability of atorvastatin calcium trihydrate (ATV), while maintaining oral compatibility.Method: Four different methods, i.e., physical mixing (PM), fusion (F), solvent evaporation (SE) and kneading (K), as well as three different excipients i.e. croscarmellose sodium (CCS), microcrystalline cellulose (MCC) and lactose (LAC) were used to formulate various drug-carrier combinations.Results: In SE method, the rank order of magnitude of drug release was CCS > LAC > MCC, while in fusion and kneading methods, the rank order of release was MCC > CCS > LAC and MCC > CCS > LAC, respectively. Drug release of atorvastatin was maximum (103 %) in FM2 formulation. However,this formulation was non-compatible based on spectroscopic analysis. In contrast, SC2 formulations at 1:2 ratio were compatible in terms of cumulative drug release (99 %), and based on spectroscopi...
BioMed research international, 2014
The objective of the present study was to develop bilayer tablets of atorvastatin and atenolol that are characterized by initial fast-release of atorvastatin in the stomach and comply with the release requirements of sustained-release of atenolol. An amorphous, solvent evaporation inclusion complex of atorvastatin with β -cyclodextrin, present in 1 : 3 (drug/cyclodextrin) molar ratio, was employed in the fast-release layer to enhance the dissolution of atorvastatin. Xanthan gum and guar gum were integrated in the sustained-release layer. Bilayer tablets composed of sustained-release layer (10% w/w of xanthan gum and guar gum) and fast-release layer [1 : 3 (drug/cyclodextrin)] showed the desired release profile. The atorvastatin contained in the fast-release layer showed an initial fast-release of more than 60% of its drug content within 2 h, followed by sustained release of the atenolol for a period of 12 h. The pharmacokinetic study illustrated that the fast absorption and increase...
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.