FORMULATION DEVELOPMENT AND EVALUATION OF ATORVASTATIN CALCIUM LIQUISOLID TABLETSHTML Full Text
FORMULATION DEVELOPMENT AND EVALUATION OF ATORVASTATIN CALCIUM LIQUISOLID TABLETS
Purushottam R. Patil *, Paresh R. Mahaparale and Khalid U. Shaikh
Department of Pharmacy, Government College of Pharmacy, Osmanpura, Aurangabad - 431005, Maharashtra, India.
ABSTRACT: The solubility and dissolution properties of any drug are vital determinants of its oral bioavailability. The aim of this study was to increase the dissolution rate of poorly soluble drug Atorvastatin calcium by delivering the drug as a liquisolid compact, prepared by using PEG as a solvent, Avicel PH 102 as carrier, silica, and lactose are used as coating materials. Sodium starch glycolate was used as super disintegrants and evaluated for their flow properties, drug excipient compatibility by FT-IR, DSC, respectively. Dissolution studies for liquisolid formulation and directly compressed tablet were carried out at a buffer pH 6.8 and found an increase in drug release of 101.71% and 80.09% at 45 min, respectively.
Liquisolid compacts, Atorvastatin Calcium, Dissolution rate, PEG-400
INTRODUCTION: In most of the pharmaceutical industry, major challenges in drug development is poor water solubility of drugs. New Chemical Entitles (NCE) do not enter the market due to their poor solubility. The liquisolid technique is a new method used to change the dissolution rate of poor soluble drugs. The dissolution is the rate-limiting step for the drug absorption for BCS class II (low solubility and higher permeability) drugs and BCS class IV (low solubility and low permeability) drugs in the biopharmaceutical classification system 1.
Different techniques have been reported in many literatures to improve the dissolution rate are:
- Reduce particle size i.e., nanonization, micronization.
- To increase surface area.
- Use of surfactant
- Use of prodrug and drug derivatization.
- Formulation of solid solution and amorphous form.
TABLE 1: BCS DRUG CLASSIFICATION 2
Among the various techniques are used to overcome the solubility issue. Several researchers reported that the formulation of liquisolid tablet is one of the most promising techniques for drug dissolution 3.
Concept of Liquisolid Formulation: When the drug dissolved in the liquid vehicle is incorporated into a carrier material which has a porous surface and closely matted fibers in its interior as cellulose, both absorption and adsorption take place.
The liquid initially absorbed in the interior of the particle is capture by its internal structure. After saturation, adsorption of the liquid on to the internal-external surface of the porous carrier particle occurs. Then the coating materials having high adsorption properties and a large specific surface area that provides the liquisolid system the desirable flow characteristics 4.
FIG. 1: CONCEPT OF LIQUISOLID SYSTEM
The non-volatile solvent present in the liquisolid system provides wetting of the drug particle by reducing the surface tension between dissolution medium and tablet surface, thus increasing in wettability and effective surface area for dissolution, which enhance the bioavailability of the drugs 5, 6.
Composition of Liquisolid Tablet:
Carrier Materials: Carrier material should possess porous surface and matted fibers in the interior, which are involved in the sorption process and improve the effective surface area for dissolution. Examples, Starch, Lactose, Sorbitol, various grades of cellulose 7.
Coating Materials: Coating material should be a material possessing fine and highly adsorptive particles, which contributes to covering the wet carrier particles and displaying a dry-looking powder by adsorbing any excess liquid. The coating material is required to cover the surface. Coating materials are very fine (10nm - 5000nm) examples colloidal silica, cab-o-sil MS, Aerosil 200, Syloid 244FFP 8.
Non-volatile Solvent: It should be inert, ability to dissolve the amount of drug, high boiling point, water-miscible, and not viscous in organic solvent system. Examples polyethylene glycol, Liquid PEG, polysorbate (Tween 80), fixed oil etc. 9
Disintegrants: Which are used to solubility enhancement of drug. Examples Crospovidone, sodium starch glycolate (pumogel, Explotab).
Drugs: Drugs should be poorly soluble or insoluble in water especially BCS class II and BCS class IV drugs 10.
MATERIALS AND METHODS:
Materials: Atorvastatin calcium was a gift sample procured from Wockhardt Pvt. Ltd, Aurangabad. Avicel PH 102, Polyethylene glycol, Silica, Lactose, Sodium starch glycolate, Magnesium stearate, cross carmellose sodium are purchased from Deepa chemicals Ltd. Aurangabad.
Calibration Curve of Atorvastatin Calcium: Accurately weigh about 50 mg of Atorvastatin calcium and dissolved in 50 ml of Phosphate buffer pH 6.8 in 50 ml volumetric flask and finally volume is adjusted to 50 ml (µg/ml). The standard solution of Atorvastatin calcium was subsequently diluted with pH 6.8 buffer to obtain a serial dilution containing 10, 20, 30, 40, and 50 µg/ml. The absorbance of the above dilutions measured on a spectrophotometer at 246 nm using pH 6.8 buffer as blank 11. The concentration of Atorvastatin calcium used, and the corresponding absorbance is given in Table 6. The absorbance was plotted against concentration, as shown in Fig. 2.
Determination of λmax of Atorvastatin Calcium: To determine the λ max of the Atorvastatin calcium spectra run in the spectrum by the UV spectroscopy is a must. The highest concentration of the solution i.e., 50µ/ml, is used to determine the λmax in the range of 200-400 nm.
Method of preparation of Liquisolid Compacts: Firstly, BCS class II drug (Atorvastatin calcium) is dispersed in a non-volatile vehicle (PEG 400). Then a binary mixture of carrier coating materials (Microcrystalline cellulose i.e., Avicel 102 as the carrier powder and as the coating material in a ratio of 20:1, 30:1, 40:1) was added to the mixture containing the drug and PEG 400 under continuous triturating in a mortar and pastel. Finally, disintegrant (sodium starch glycolate) was mixed and triturate with the resultants mixture. So that by using this methodology, we get liquisolid compact of Atorvastatin calcium. Then compress the tablets of Atorvastatin calcium by using a Tablet punching machine. This is the general method for the preparation of the liquisolid compact 12, 13.
Formulation of Conventional Tablets of Atorvastatin Calcium: Conventional tablets were prepared by mixing the drug with a micro-crystalline cellulose Silica mixture (ratio MCC: Silica was 20:1) for a period of 10 min. The blend was mixed with (Soduim Starch Glycolate as disintegrants) for 10 min, and compressed using a manual tablet punching machine. Sufficient compression load was applied in order to produce tablets with the hardness 3.5 kg/cm2. This formulation denoted as DCT 14.
Evaluation of Pre-compression Liquisolid Compact:
Angle of Repose: Fixed funnel and the free-standing cone method were employed to measure the angle of repose. A funnel was secured with its tip at a given height (H) above a graph paper placed on a flat horizontal surface. The powders were carefully poured through the tip of the funnel. The mean radius (r) of the base of the conical pile was determined, and measured the height (h) of the pile, after that, the tangent of the angle of repose was determined. The angle of repose of powder (drug) is determined by using the following formula 15.
Tan θ = h/r
θ = tan-1 (h/r)
Where θ = angle of repose; h = height of pile; r = radius of the base of the pile
Bulk Density: The loose bulk density and tapped density were determined by using bulk density apparatus. Apparent bulk density was determined by pouring the blend into a graduated cylinder. The bulk volume (Vb) and the weight of the powder (M) were determined. The bulk density was calculated using the formula
BD = M / Vb
Where M is the mass of powder; Vb is the bulk volume of powder.
Tapped Density: It is the ratio of the mass of the powder to the tapped volume of the powder. Volume determined using a measuring cylinder. Weight quantity of powder-filled in cylinder and volume occupied by measuring cylinder tapped for 500 times and volume occupied by measuring cylinder determined.
TD = M / Vt
Where, M is the mass of powder and Vt is the tapped volume of the powder.
TABLE 2: RELATIONSHIP BETWEEN ANGLE OF REPOSE AND FLOW PROPERTY
|Angle of repose (°)||Flow Property|
|3 0- 40||Passable|
|˃ 40||Very Poor|
Carr’s Index: The compressibility index (Carr’s index) is a measure of the propensity of a powder to be compressed. It is determined from the bulk and tapped densities and is calculated using the formula.
Carr’s index (%) = (TD – BD) × 100 / TD
Hausner’s Ratio: A Flow property of powder mixture can be determined by Hauser’s ratio. It is determined from the bulk and tapped densities and is calculated using the formula. The relationship between Hauser’s ratio and flow behavior was reported in table 15.
Hauser’s Ratio =TD/BD
Where, TD is the tapped density, and BD is the bulk density
TABLE 3: RELATIONSHIP BETWEEN CARR’S INDEX, FLOW CHARACTER AND HAUSER’S RATIO
|Consolidation Index (%) (Carr’s index)||Flow
|Hauser’s ratio (%)|
|11 – 15||Good||1.12-1.18|
|16 – 25||Fair to passable||1.19-1.34|
|26 – 31||Poor||1.35-1.45|
|32 – 37||Very poor||1.46-1.59|
|>38||Very very poor||>1.60|
Evaluation of Liquisolid Tablets:
Appearance and Shape: The general appearance of the tablets includes morphological characteristics like size, shape, color, odor, etc. Also, tablets may have lines, break-marks, and many symbols on the surface of tablets.
Uniformity and Thickness and Diameter: The uniformity of diameter and thickness was measured by using Vernier caliper. The average diameter and thickness of the tablets were calculated. The test passed if none of the individual diameter and thickness values deviated by >5% of the average.
Weight Variation Test: To study the weight variation, twenty tablets were taken, and their weight was determined individually and collectively on a digital weighing balance. The average weight of one tablet was determined from the collective weight. The weight variation test would be a satisfactory method of determining the drug content uniformity. The percent deviation was calculated using the following formula 15.
% Deviation = (Individual weight /Average weight) × 100
Hardness Test: The hardness of formulated liquisolid tablets was assessed using a Pfizer hardness tester, and the mean hardness of three tablets was determined.
Friability Test: The friability of the prepared liquisolid tablets was measured in a Roche type apparatus, and the percentage loss in weight was calculated 1.
% Friability = (Loss in weight / Initial weight) × 100
Maximum weight loss = Less than 1%
Drug Content: Five tablets were crushed, and powder equivalent to the weight of one tablet was dissolved in solvent SLS-water (40mg/ml), and volume is made up to 100ml. The solution was filtered through Whatman filter paper no. 41. The filtrate was analyzed for drug contended at λmax 246 nm by using UV spectroscopy 16.
Instrumental Analysis of Drug:
FT-IR Spectra of the Drug: FT-IR spectrometer IR 200 Thermo Electron Corporation used in Attenuated total reflectance (ATR) mode for collecting FT-IR spectra of samples. By using IR study the functional group of drug and excipients may be identified. The spectra’s were collected over the range of 4000-400 cm-1. 17
Differential Scanning Calorimetry Studies: DSC thermogram of the optimized Liquisolid Compacts (10mg sample) was recorded using automatic thermal analyzer. The DSC is used to evaluate drug-excipient interaction 18.
Disintegration Test: Six tablets were taken randomly from each batch and placed in USP disintegration apparatus baskets Apparatus was run for 10 min, and the basket was lifted from the fluid, observe whether all of the tablets have disintegrated.
Dissolution Study: Dissolution is the process by which a solid solute enters a solution. Pharmaceutically, it may be defined as the amount of drug substance that goes into solution per unit time under standardized conditions of liquid/solid interface, temperature, and solvent composition. Dissolution kinetics is important in determining the bioavailability of a drug. The dissolution study of Atorvastatin calcium compact was performed. Dissolution study of Atorvastatin calcium is carried out in the buffer pH 6.8 by the paddle type apparatus 19.
TABLE 4: DISSOLUTION PARAMETERS
|Dissolution Apparatus||USP-type ІІ Apparatus (Paddle)|
|Agitation speed||50 rpm|
|Dissolution medium||Buffer PH 6.8|
|Volume of dissolution medium||900ml|
|Temperature||37± 0.5º C|
Comparison with Marketed Product: The developed product was quantitatively evaluated and assessed for a tablet's properties, and product quality was monitored for the various specification. The following standards and quality control tests were carried out on marketed tablets for comparative evaluation of developed and marketed product, and observation was reported in Table 5 and comparative dissolution profile of developed and marketed product was presented in Table 5.
Details of Marketed Product:
Manufacturer: Sun Pharma
Brand Name: Aztor 40 mg
Batch no.: EMP230Mfg. Date: 11/2015
Exp. Date: 10/2018
RESULTS AND DISCUSSION:
TABLE 5: COMPOSITION OF DIFFERENT FORMULATION OF LIQUISOLID COMPACTS
|Avicel PH 102||300||280||280||260||300||260||300||280||260|
|PEG 400 (ul)||81||92||70||92||92||81||70||81||70|
|Sodium starch glycolate||20
|Total wt of tablets (mg)||400
Determination of λmax by UV Spectrophotometer: Solution containing 10 µg/ml of Atorvastatin calcium was prepared and scanned over a range of 2000-400 nm against buffer pH 6.8 as blank using UV Spectrophotometer 20. The λmax was obtained at 246 nm. The plot of absorbance against wavelength is shown in Fig. 2.
FIG. 2: SPECTRUM OF ATORVASTATIN CALCIUM DRUG
TABLE 6: CALIBRATION CURVE OF ATORVASTATIN CALCIUM IN BUFFER PH 6.8 AT λmax 246 nm
|S. no.||Concentration (µ/ml)||Absorbance|
TABLE 7: STANDARD CALIBRATION CURVE STATISTIC
|1||Absorbance maximum||246 nm|
|4||Correlation coefficient (r2)||0.998|
|5||Equation||Y=0.02971 X + 002924|
FIG. 3: CALIBRATION CURVE OF ATORVASTATIN CALCIUM IN pH 6.8 BUFFER AT λmax 246 nm
Instrumental Analysis of Drug Excipients and the Liquisolid Compact:
IR Spectra of Drug Atorvastatin Calcium: The IR spectrum of Atorvastatin calcium was recorded over a range of 4000 cm-1 to 400 cm-1. The spectrum obtained was concordant with the reference as depicted in Fig 4.
The assignments as shown in Table 8 for Atorvastatin calcium. The graph shows all the ranges of the functional groups of Atorvastatin Calcium. Hence, it can be concluded that the drug was Atorvastatin calcium.
FT-IR spectroscopy of Liquisolid Compact: FT-IR spectroscopy was performed on the pure drug, and a Physical mixture of the formulations was prepared. The characteristic peak in drug and excipients vanished IR spectra Liquisolid system that which may be due to complete solubilization or amorphization of the drug in the non-volatile liquid vehicle. From the comparison of both IR spectra, that is, IR spectra of drug & IR spectra of Liquisolid compact, results were obtained that intensity of peak decreased, so that peak of functional was shifted towards lower ranges. Results were reported in Fig. 5.
FIG. 4: IR SPECTRA OF ATORVASTATIN CALCIUM
FIG. 5: IR SPECTRA OF THELIQUISOLID COMPACT
As shown in Fig. 5 the ranges of the functional group are not changes in liquisolid compact. Therefore, the drug and excipients are compatible to each other. The IR spectra show that the excipients and drug compatible with each other. According to the following table. It proves that excipients do not interact with each other.
TABLE 8: COMPARISON OF THE PEAKS OF FUNCTIONAL GROUPS OBSERVED IN IR SPECTRA
|Atorvastatin Calcium (Pure)||Liquisolid compact|
Differential Scanning Calorimetry Study (DSC) of Drug and Liquisolid Compact:
DSC Study for the Atorvastatin Calcium: DSC thermogram of Atorvastatin calcium as shown in the thermogram in Fig. 6. It can be seen that endothermic peak with onset at 145.31 ºC and end set 172.87 ºC and also show the sharp peak at 161.06 ºC which corresponds to the melting point of Atorvastatin calcium (159.5 -160.5 ºC).
Fig. 6 shows that the DSC results show the appropriate melting point in the standard melting point range. Therefore, it confirms that the drug was Atorvastatin calcium.
FIG. 6: DSC OF ATORVASTATIN CALCIUM
FIG. 7: DSC OF LIQUISOLID COMPACT
DSC thermogram of Atorvastatin calcium as shown in the thermogram in Fig 6. It can be seen from DSC thermogram of liquisolid compact shown in Fig. 7 that endothermic peak of the pure drug at 161.06 ºC was vanished. According to the DSC results, we can conclude that there may in complete solubilization of drug in liquisolid complex.
Hence, we can conclude that there may be compatibility of the drug with excipients in liquisolid compact.
TABLE 9: AMOUNT OF VARIABLES IN 32 FACTORIAL DESIGN BATCHES
|Coded Value||Actual Value|
|X1 (µl)||X2 (mg)|
TABLE 10: FACTORIAL BATCHES EXPERIMENTAL DESIGN
|Formulation Code||Coded Value||Total Weight of Tablet (mg)|
Flow Properties of Liquisolid Compacts: Bulk density may influence the compressibility, tablet porosity, dissolution, and other properties and depends on the particle size, shape, and tendency to particle adhere together. The bulk density of granules was found to be between 0.35-0.46 gm/cm3. The values indicate the good packing capacity of granules. The tap density of the granules of factorial batches was found in the range of 0.43-0.56 gm/cm3; the bulk density and tap density was used to calculate the percent compressibility of the granules.
The carr’s index of the granules observed between 13.67-17.97, indicating good compressibility of the granules. The value of the Hausner’s ratio was found to be between 1.16-1.22, indicating good flowability.
TABLE 11: EVALUATION OF PRE-COMPRESSION LIQUISOLID COMPACT
|Formulation code||Bulk density mg/cm3||Tapped density gm/cm3||Carr’s index (%)||Angle of
Response Surface Plot for % Drug Release:
FIG. 8: RESPONSE SURFACE PLOTS
ANOVA for Response Surface Linearity Model:
TABLE12: ANOVA MODEL PREDICTION
|Partial Sum of Squares Type III|
|Source||Sum of Squares||Df||Mean Square||F Value||P-Value Prob > F||Prediction|
TABLE 13: EVALUATION OF TABLET PROPERTIES OF FACTORIAL BATCHES
|Weight Variation# (mg±SD)||Friability# (%)||Drug Content* (%)||D.T. (sec)|
|F1||Off white, circular, 10mm, flat faced||3.63±0.07||3.4±0.04||245±1.14||0.532±0.15||96.54±1.10||92|
|F2||Off white, circular, 10mm, flat faced||3.60±0.08||3.7±0.11||248±1.45||0.410±0.23||98.34±0.94||85|
|F3||Off white, circular, 10mm, flat faced||4.12±0.12||3.1±0.5||233± 1.17||0.429±0.24||100.64±0.28||87|
|F4||Off white, circular, 10mm, flat faced||4.05±0.45||3.9±0.08||258±1.4||0.560±0.36||99.51±1.14||90|
|F5||Off white, circular, 10mm,flat faced||3.39±0.48||4.3±0.13||279±1.8||0.601±0.64||99.92±0.78||94|
|F6||Off white, circular, 10mm, flat faced||3.35±0.69||3.3±0.58||281±1.6||0.589±0.27||102.45±0.84||88|
|F7||Off white, circular, 10mm, flat faced||4.08±0.58||3.7±0.12||253±1.7||0.572±0.38||97.21±0.69||91|
|F8||Off white, circular, 10mm, flat faced||4.42±0.46||3.8±0.19||288±1.3||0.583±0.91||98.14±0.49||87|
|F9||Off white, circular, 10mm, flat faced||4.23±0.71||3.6±0.07||254±1.1||0.581±0.04||100.35±1.14||92|
*All values are expressed as mean ± SD, n=3; # All values are expressed as mean ± SD, n=10; # All values are expressed as mean ± SD, n=10
TABLE 14: ASSAY VALUES OF DIFFERENT FORMULATIONS (N=3±SD)
|Formulation||% Drug content|
The in-vitro Dissolution Study of Atorvastatin Calcium Liquisolid Tablets: The result of in-vitro percentage drug amount of drug released at different time intervals plotted against time to obtain the release profile.
TABLE 15: % OF CUMULATIVE DRUG RELEASE OF FORMULATION F1-F3
|Time (min)||Cumulative drug release %|
|F1 F2 F3|
FIG. 9: % OF CUMULATIVE DRUG RELEASE OF FORMULATION F1- F3
TABLE 16: % OF CUMULATIVE DRUG RELEASE OF FORMULATION F4- F6
|Time (min)||Cumulative Drug Release %|
All the liquisolid tablets show thee higher drug release than the (DCT) Direct compressed tablets due to the fact that the drug is already in a solution of PEG 400 while at the same time it is carried by the powder particles (microcrystalline cellulose and silica), thus its release is accelerated due to its increased wettability and surface availability to the dissolution medium.
FIG. 10: % OF CUMULATIVE DRUG RELEASE OF FORMULATION F4- F6
TABLE 17: % OF CUMULATIVE DRUG RELEASE OF FORMULATION F7-F9
|Time (min)||Cumulative Drug Release %|
FIG. 11: % CUMULATIVE DRUG RELEASE OF FORMULATION OF F7-F9
TABLE 18: COMPARATIVE EVALUATION OF DEVELOPED AND MARKETED PRODUCT
|Evaluation parameter||Developed product||Marketed
|Appearance||409.7mg, white coloured,10 mm, round flat faced||275 mg off white coloured, 8mm, round biconvex faced|
|Hardness (Kg/cm2 )||3.1±0.5||2.5± 0.06|
|Drug Content (%)||101.64 %||102.21%|
|In-vitro DT (sec)||87 sec||85 sec.|
|Cumulative % drug release||101.71±0.37||103.16±1.03|
TABLE 19: COMPARATIVE DISSOLUTION PROFILE OF DEVELOPED AND MARKETED PRODUCT
|Cumulative % drug release|
|Developed Product (F3)||Marketed Product|
All values are mean ± SD, N=3
FIG. 12: DISSOLUTION PROFILE OF F3, CONVENTIONAL TABLET, AND MARKETED FORMULATION
CONCLUSION: In this present work, nine formulations of Atorvastatin calcium tablets were successfully prepared by using liquisolid compact technique. Cumulative percentage drug release of Atorvastatin calcium liquisolid tablets is faster than conventional tablets. Liquisolid technique changes the properties of Atorvastatin calcium particle by simply dispersing the drug particles in non-volatile solvent PEG 400, which increases the wetting property and surface area of the drug particle to improve the dissolution profile and might be oral bioavailability of the drug.
ACKNOWLEDGEMENT: Authors are thankful to Dr. V. K. Mourya, Principal Government College of Pharmacy, Aurangabad, for providing the necessary facilities to carry out this work.
CONFLICTS OF INTEREST: There is no conflict of interest amongst the authors and coauthors.
- Hamsanandini J, Parthiban S and Vikneswari A: Dissolution enhancement techniques of poorly soluble drugs by liquisolid compacts. Int J Res Pharm Nano Sci 2014; 3(3): 177-85.
- Korni R: Liquisolid technique: an approach to enhance the dissolution rate of olanzapine. Indian J Pharm Sci 2018; 80(6): 1003-10.
- Cherukuri S, Chappidi SR, Dindigala A and Vadla A: Liquisolid Technique : A novel approach to enhance solubility and bioavailability of BCS-II drugs. Int J Pharm Res Sch 2012; 3(7): 108-15.
- Panda S, Varaprasad R, Priyanka K and Swain RP: Liquisolid technique: a novel approach for dosage form design. Int J Appl Pharm 2017; 9(3): 8-14.
- Derle DV: Solubility enhancement of nifedipine by using liquisolid compact technique. Indo American Journal of Pharmaceutical Research 2017: 7(02): 7740-55.
- Pravala K and Nagabandi VK: Solubility enhancement of poorly soluble drugs by using novel technique: a comprehensive review. International Journal of PharmTech Research 2020; 13(2): 80-93.
- Sinkar NB and Gondkar SB: Liquisolid systems: solubility enhancement of poor soluble drugs. World J Pharm Res 2015; 4(3): 1748-65.
- Vadlamudi MK and Dhanaraj S: Disparate practical way of doing solubility enhancement study to improve the bioavailability of poorly soluble drugs, Journal of Chemical and Pharmaceutical Res 2016; 8(1): 208-35.
- Nash RA: Suspensions. In: J Swarbrick, JC Boylan (ed). Encyclopedia of pharmaceutical technology, Marcel Dekker, 2002 Second ed Vol. 3 New York; 2045-3032.
- Kumar JK, Kumar GYS and Kumar PS: Liquisolid compacts : an effective approach towards enhancement of dissolution rate of poorly soluble drugs. Int J Pharma Chem Res 2015; 1(1): 38-45.
- Koteswari P, Sunium S, Srinivasababu P, Babu GK and Nithya PD: Formulation development and evaluation of fast disintegrating tablets of lamotrigine using liqui-solid. Int J Pharm Investig 2014; 4(4): 207-14.
- Mohammed AM and Al- Akkam EJ: preparation and in-vitro evaluation of clopidogrel bisulfate liquisolid compact. Iraqi J Pharm Sci 2018; 27(2): 135-49.
- Sravana M, Srivalli P and Rajeev T: A novel approach for improvement of solubility and bioavailability of poorly soluble drugs : liquisolid compact technique. Int J Res Pharm Biomed Sci 2012; 3(4): 1621-32.
- Wang D, Xing H, Jiang J, Chen X, Yang T and Wang D: Liquisolid technique and its applications in pharmaceutics. Asian J Pharm Sci 2017; 12(2): 115-23.
- Indian Pharmacopoeia Commission, Ministry of Health & Family Welfare, Government of India. The Indian Pharmacopoeia 2010; 138.
- Rajesh K: Formulation and evaluation of bilayer liquisolid tablets of atorvastatin calcium and felodipine. Int Res J Pharm 2013; 4(1): 138-45.
- Savkare AD and Bhavsar MR: Liquisolid techniques: a review. Int J Pharma Sci Res 2017; 8(7): 2768-75.
- Jabbar ASA and Hussein AA: Formulation and evaluation of piroxicam liquisolid compacts. Int J Pharm Pharm Sci 2013; 5(1): 132-41.
- Shah D and Patel MM: Formulation and evaluation of liquisolid compacts of olanzepine. Journal of Drug Delivery and Therapeutics 2019, 9(4): 189-02.
- Wankhede NB, Walekar SS and Sadgir PS: Liquisolid: A novel technique for dissolution enhancement of poorly water soluble drugs. Asian J Pharm Technol Innov 2014; 2(8): 77-90.
How to cite this article:
Patil PR, Mahaparale PR and Shaikh KU: Formulation development and evaluation of atorvastatin calcium liquisolid tablets. Int J Pharm Sci & Res 2021; 12(3): 1849-59. doi: 10.13040/IJPSR.0975-8232.12(3).1849-59.
All © 2013 are reserved by the International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
P. R. Patil *, P. R. Mahaparale and K. U. Shaikh
Department of Pharmacy, Government College of Pharmacy, Osmanpura, Aurangabad, Maharashtra, India.
08 January 2020
18 May 2020
21 May 2020
01 March 2021