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1 2 3 Available online at www.ijtpls.com International Journal of Trends in Pharmacy and Life Sciences Vol. 3, Issue: 4, 2017: 55-66. FORMULATION AND IN VITRO EVALUATION OF LIQUI SOLID 5 COMPACT OF FELODIPINE Donthula Priyanka*, L. Matsyagiri, K.Pavan Kumar Department of Pharmaceutics, RBVRR Women s College of Pharmacy, Affiliated to Osmania University- Hyd, Barkatpura, Hyderabad. Telangana, India E.Mail: pinki.priya14@gmail.com ABSTRACT The main aim of present work, Formulation and in vitro evaluation of liquid solid compact of Felodipine is to increase Bio-availability using different ratios of co solvents. In this technique actual mechanism of increasing solubility is the wetting of drug particle by using cosolvent and increase in surface area of the drug particle by preparing in the form of Liquisolid compact. The study shows that the solubility of Felodipine is very less in water and hence the various non-volatile solvents having more solubility than the water are used among them tween-80, PEG, glycerol, propylene glycol have shows good solubility of Felodipine in water.among them propylene glycol have shown increased solubility of Felodipine, Hence propylene glycol is selected for the preparation of liquisolid compacts. Microcrystalline cellulose and aerosil was selected as carrier and coating material. Then Cros-caramellose sodium was added as the superdisintegrant and magnesium sterate acts as Glidant in the formulation. The FTIR and DSC spectral studies showed no interaction of drug with polymer and excipients. F5 formulation has been selected as the optimized formulation among all the other formulation and percentage drug release for F5 Formulation was 98.36 % at the end of 60 mins. The Optimized formulation F5 was kept in Kinetic release models; it follows Higuchi model and its regression value R2 Was 0.987. Finally the optimized formulation (F5) was kept for stability studies For 15 days, 30 days, 45 days. There is no significant difference in the values obtained before and after stability of final optimized formulation. Key Words: Cosolvents, Felodipine, Free flowing, Liquisolid technique, Wetting *Corresponding Author: D. Priyanka, RBVRR Women s College of Pharmacy, Affiliated to Osmania University-Hyd, Barkatpura, Hyderabad. Telangana, India. Tel.: +91-9966463776; Received: 20/04/2017 Revised: 18/0/5/2017 Accepted: 25/05/2017 INTRODUCTION The solubility is defined as a maximum quantity of solute that can dissolve in a certain quantity of solvent or quantity of solution at a specified temperature. Almost More than 90% drugs are orally administered and their Drug absorption, bioavailability, pharmacokinetic profile highly dependent on solubility of that compound in aqueous medium. More than 90 % of drugs are approved since 1995 have poor solubility. It is estimated that 40 % of active new chemical entities (NCEs) identified in combinatorial screening programs employed by many pharmaceutical companies are poorly water soluble. Low aqueous solubility is the major problem encountered in formulation development of new chemical entities as well a, s for the generic development. The insufficient dissolution rate of the drug is the limiting factor in the oral bioavailability of poorly water soluble compounds. These poorly water soluble drugs are allied with slow drug absorption leading to inadequate and variable bioavailability and gastrointestinal mucosal toxicity of drugs. Poor water soluble drugs belong to BCS class II and class IV. [1-9]. Advantages Increased bioavailability of poorly water soluble drugs. Less production cost compared to soft gelatin capsules. Priyanka D et al. Int J Trends in Pharm & Life Sci. 2017: 3(4); 55-66. 55

Suitable for industrial production. Drug release can be modified by changing suitable ingredients. Rapid release liquisolid tablets (or) capsules exhibit enhanced in vitro & in vivo drug release compared to their commercial products. Sustained released tablets (or) capsules of water insoluble drugs exhibit zero order release. It can be used to formulate liquid medications. Used in controlled drug delivery. Disadvantages Liquisolid system requires low drug loading capacities. Requires more efficient excipients and it should provide faster drug release with smaller tablet size. Higher amounts of carrier and coating materials are required [10]. Limitations Not suitable for formulation of high dose water insoluble drugs. If more amounts of carrier is added it increase the flow properties of powder, it may increases the tablet weight too, hence it is difficult to swallow. It does not require chemical modification of drugs. Acceptable compression may not be achieved because the liquid drug may be squeezed out during compression resulting in unsatisfactory tablet weight Applications This technology is powerful tool to improve the bioavailability of poorly water soluble drugs Rapid release rate Suitable for controlled release Applicable in probiotics. The technique of liquisolid preparation is used to formulate a drug solution in solid dosage forms. Drug solution is generally, prepared by dissolving the drug in non-volatile water- MATERIALS AND METHODS Materials: Felodipine was a gift sample from Dr. Reddy s Lab., Tween 80, PEG 400, Aerosil, Micro crystalline cellulose, cross Carmellose sodium, magnesium Stearate provided by S.D fine chemicals Mumbai. Method of preparation: Preparation of liquicompact tablets prepared by direct compression method. The Felodipine was dissolved in Propylene glycol and a homogenous drug solution was prepared. Next, the calculated Weights (W) of the resulting liquid medicaments were incorporated into the calculated quantities of the carrier material and mixed thoroughly. The resulting wet mixture was then blended with the calculated amount of the coating material using a standard mixing process to forms simple admixture. The prepared Liquisolid powder systems were manually compressed into multi stationary punching machine. Evaluation of tablets: To design tablets and later monitor tablet production quality, quantitative evaluation and assessment of tablet chemical, physical and bioavailability properties must be made.[11-19] Weight variation test: It is desirable that all the tablets of a particular batch should be uniform in weight. If any weight variation is there, that should fall within the prescribed limits: ±10 % for tablets weighing 300 mg or less; ±7.5 % for tablets weighing 300-315 mg; ±5 % for tablets weighing more than 315 mg; Twenty tablets were taken randomly and weighed accurately and the average weight calculated Hardness test: This is the force required to break a tablet in a diametric compression. Hardness of the tablet is determined by Stock s Monsanto hardness tester which consists of a barrel with a compressible spring. The tablet hardness of 4-6 kg/cm 2 is considered as suitable for handing the tablet. Size and Thickness: Control of physical dimensions of the tablets such as size and thickness is essential for consumer acceptance and tablet-tablet uniformity. The thickness of tablet is measured by Vernier Calipers Priyanka D et al. Int J Trends in Pharm & Life Sci. 2017: 3(4); 55-66. 56

scale. Tablet thickness should be controlled within a ±5%. In addition thickness must be controlled to facilitate packaging. Friability test: It is performed to evaluate the ability of tablets to withstand abrasion in packing, handling and transporting. Initial weight of 20 tablets is taken and these are placed in the roche friabilator, rotating at 25 rpm for 4min. The difference in the weight is noted and expressed as percentage. It should be preferably between 0.5 to 1.0 %. In vitro Disintegration test: For most tablets the first important step toward solution is break down of tablet into smaller particles or granules, a process known as disintegration. This is one of the important quality control tests for disintegrating type tablets. Six tablets are tested for disintegration time using USP XXII apparatus. Disintegration type conventional release tablets are tested for disintegrating time. Drug excipients compatibility study FTIR: Completely dried potassium bromide was transferred into a mortar. About 2 % of pure drug or with excipients was weighed in digital balance, mixed and grinded to a fine powder. Two stainless steel disks were taken out of the desiccators. A piece of the pre-cut cardboard (in the tin can next to the oven) on top of one disk was placed and cut out hole was filled with the finely ground mixture. The second stainless steel disk was kept on top and transfers the sandwich onto the pistil in the hydraulic press. With a pumping movement, hydraulic pump handle moved downward. The pistil will start to move upward until it reaches the top of the pump chamber. Then, the pump handle moved upwards and continued pumping until the pressure reaches 20,000 prf. Rest for a few seconds and with the small lever on the left side, the pressure was released. Removing of the disks and pulling apart. Obtained film was homogenous and transparent in appearance. Than inserted into the IR sample holder and attach with scotch tape and run the spectrum.[20] Differential scanning calorimeter: The physical nature of the prepared LS optimized mixture and SD optimized mixture was studied by DSC. The conversion of crystalline drug into amorphous form was studied. DSC analysis was performed using TA Instruments Perkin-Elmer pyris differential scanning calorimeter (DSC). The instrument was calibrated with indium standard. 3-5 mg samples were weighed and placed in a closed, hermetic sample pans with pin hole. Thermograms were obtained by heating the sample at a constant rate 10 C /min. A dry purge of nitrogen gas (50 ml/min) was used for all runs. Samples were heated from 0 C to 250.0 C. The melting point, heat of fusion, disappearance of the crystalline sharp peak of the drug and appearance of any new peak and peak shape were noted. The pure drug and Aerosil were analyzed by DSC in same manner and the melting point and heat of fusion values were noted. The thermogram of the LS optimized formulation was superimposed with that of pure drug and Aerosil.[21] In-vitro dissolution study: Dissolution studies were carried out for all the formulations combinations in triplicate, employing USP XXVII paddle method and 900ml of ph 6.8 phosphate buffer as the dissolution medium. The medium was allowed to equilibrate to temp of 37+ 0.5 C. Tablet was placed in the vessel and the vessel was covered the apparatus was operated for 1 hr in ph 6.8 phosphate buffer at 50 rpm. At definite time intervals of 5 ml of the aliquot of sample was withdrawn periodically and the volume replaced with equivalent amount of the fresh dissolution medium. The samples were analyzed spectrophotometrically at 230 nm using UV-Spectrophotometer. [22] Release Kinetics [23-26] The analysis of drug release mechanism from a pharmaceutical dosage form is an important. As a modeldependent approach, the dissolution data was fitted to five popular release models such as zero-order, firstorder, diffusion and exponential equations. Zero Order Release Kinetics: It defines a linear relationship between the fraction of drug released versus time. Q = k o t Where, Q is the fraction of drug released at time t and k o is the zero order release rate constant. A plot of the % of drug released against time will be linear if the release obeys zero order release kinetics. First Order Release Kinetics: Wagner assuming that the exposed surface area of a tablet decreased exponentially with time during dissolution process suggested that drug release from most of the slow release Priyanka D et al. Int J Trends in Pharm & Life Sci. 2017: 3(4); 55-66. 57

tablets could be described adequately by apparent first-order kinetics. The equation that describes first order kinetics is In (1-Q) = - K 1 t Where, Q is the fraction of drug released at time t and k 1 is the first order release rate constant. Thus, a plot of the logarithm of the fraction of drug remained against time will be linear if the release obeys first order release kinetics. Higuchi s equation: It defines a linear dependence of the active fraction released per unit of surface (Q) on the square root of time. Q=K 2 t ½ Where, K2 is the release rate constant. A plot of the fraction of drug released against square root of time will be linear if the release obeys Higuchi equation. This equation describes drug release as a diffusion process based on the Fick s law, square root time dependant. Power Law: In order to define a model, which would represent a better fit for the formulation, dissolution data was further analyzed by Peppas and Korsemeyer equation (Power Law). M t /M = K.t n Where, M t is the amount of drug released at time t and M is the amount released at time, thus the M t /M is the fraction of drug released at time t,k is the kinetic constant and n is the diffusional exponent. A plot between log of M t /M against log of time will be linear if the release obeys Peppas and Korsemeyer equation and the slope of this plot represents n value. Table 1: Diffusion exponent and solute release mechanism for cylindrical shape Sl. No Diffusion Exponent Overall solute diffusion mechanism 01 0.45 Fickian diffusion 02 0.45<n<0.89 Anomalous (non-fickian) diffusion 03 0.89 Case II transport 04 n>0.89 Super Case II transport Stability studies: The purpose of stability testing is to provide evidence on how the quality of an active substance or pharmaceutical product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light. Also, the stability of excipients that may contain or form reactive degradation products, have to be considered. [27-30] Table 2: Objectives of Stability Testing Objective Type of study Use To select adequate (from the viewpoint of stability) formulations and containerclosure systems Accelerated Development of the product To determine shelf-life and storage conditions Accelerated and realtime Development of the product and of the registration dossier To substantiate the claimed shelf-life Real-time Registration dossier To verify that no changes have been introduced in the formulation or manufacturing process that can adversely affect the stability of the product Accelerated and realtime Quality assurance in general, including quality control. Priyanka D et al. Int J Trends in Pharm & Life Sci. 2017: 3(4); 55-66. 58

Abosorbance RESEARCH ARTICLE e-issn: 2454-7867 RESULTS AND DISCUSSION Table 3: Standard calibration curve of Felodipine in ph 6.8 phosphate solution Sl. No Concentration (µg/ml) Absorbance 0 00 0 1 10 0.0575 2 20 0.1222 3 30 0.1756 4 40 0.2356 5 50 0.2948 0.5 Standard graph of felodipine y = 0.0059x + 0.00 S 0 e 4 ries1 R² = 0.9996 0 10 20 30 40 50 60 Concentration ( mcg/ml) Linear (Series1) Fig.1: Standard calibration curve of Felodipine 1.0 0.9 1991.00 1891.04 1316.29 934.34 1080. 01 4 0 6 5.39 698.48 2475.95 2599.44 0.8 2857.38 1166.69 3925.37 3565.24 3300.74 1944.481794.16 1867.97 Singl 0 e.7 channel 3699.97 2927.10 1284.81 3894.25 1726.18 3809.97 1917.18 1626.52 0.6 3844.51367 3 8 6. 2 8 0 6.47 183 1 5 7.8 7 1 0.55 1676.34 1426.56 1243.03 1706.40 1477.61 3874.28 1614.95 0.5 1740.86 3829.05 3648.97 1646.7 1 9 532.5 1 8 395.91 0.4 3743.64 1694.07 1464.98 3861.02 1564.15 977.44 1046.01 857.46 781.16868.40 617.07 645.09 572.83 0.3 1515.85 1548.29 2362.99 3500 3000 2500 Wave number cm-1 2000 1500 1000 Fig. 2: Infrared spectrum of pure Felodipine Priyanka D et al. Int J Trends in Pharm & Life Sci. 2017: 3(4); 55-66. 59

2350.17 1649.014511.89 3522.79 1200.27 [%] ttance 3643.93 2897.24 2977.94 2312.36 1.22 1166.14 898.15 1138.03 874.48 670.36 1090.19 629. 01 1069.13 601.36 350 300 250 200 150 100 0 0 0Wavenumber cm0-0 0 1 Fig. 3: Infrared spectrum of pure felodipine drug with tween 80 90 2312.12 85 2956.62 934.60 T s tt [ ] 3396.62 1492.90 1169.18 893.16 75 1223.88 731.79 1460.20 70 65 1421.87 1283.82 60 1642.59 3500 3000 2500 2000 1500 1000 Wavenumber cm-1 Fig. 4: Infrared spectrum of pure felodipine drug with propylene glycol From the above figure2-6, it can be seen that, the major functional group peaks observed in spectras of Drug with all the polymers remains unchanged as compared with spectra of Felodipine. So from the above IR spectra it can be observed that there is no interaction between Felodipine and Polymers used in the formulations. Priyanka D et al. Int J Trends in Pharm & Life Sci. 2017: 3(4); 55-66. 60

Fig. 5: Differential Scanning Calorimetry of Felodipine Liquisolid compact formulation Formulation design Table 4: Formulation of Felodipine tablets (F1-F7) Ingredients (mg) F1 F2 F3 F4 F5 F6 F7 Felodipine 5 5 5 5 5 5 5 Propylene glycol 40 80 PEG-400 40 80 Tween- 80 40 80 Micro crystalline cellulose 300 400 300 400 300 400 440 Aerosil (Coating material) 60 80 60 80 60 80 60 Cros Caramellose sodium 30 30 30 30 30 30 30 Magnesium Stearate 5 5 5 5 5 5 5 Loading Factor: Liquid load factor and is defined as the Weight ratio of the liquid formulation(w) and the Carrier material (q) in the system Lf = W/Q,,R`` represents the ratio between the Weights of the Carrier (Q) and Coating (q) material present in the formulation R= Q/q The liquid load factor that ensures acceptable flowability (Lf) can be determined by Lf= Φ + Ψ (1/R. Loading factor was calculated for the formulations. Table 5: Loading Factor Sl. No Formulation Loading Factor R Value 1 F1 0.15 5 2 F2 0.21 5 3 F3 0.15 5 4 F4 0.21 5 5 F5 0.15 5 6 F6 0.21 5 7 F7 0.01 7.3 Factor: =Liquid medication (W)/ Carrier material (Q) Ratio (R):- Q/q Where, Q- Carrier material, q- Coating material Priyanka D et al. Int J Trends in Pharm & Life Sci. 2017: 3(4); 55-66. 61

Evaluation of felodipine tablets Table 6: Bulk density, Compressibility index, Hauser s ratio, Angle of repose of Batch Bulk density Tapped density Compressibility Hausner (gm/cm 3 )* (gm/cm 3 Angle of repose )* Index Ratio* (θ )* (%)* F1 0.4130 0.4738 12.8205 1.1470 26.33 F2 0.4027 0.4149 2.9411 1.0302 22.29 F3 0.4027 0.4149 2.9411 1.0302 24.15 F4 0.4972 0.5424 8.3333 1.0.909 23.48 F5 0.5704 0.6560 13.0434 1.1500 25.26 F6 0.5943 0.6538 9.0909 1.1000 28.78 F7 0.5418 0.5587 3.0303 1.0312 22.48 Discussion: Evaluation of Felodipine tablets is given in table 6.The pure drug Felodipine pre-formulation was found to be limits. The bulk density of various powder mixed blends prepared with different super disintegrates. Effervescent was measured by graduated cylinder. The bulk density was found in the range 0.4027 0.5943kg/cm 3. The tapped density was found in the range 0.4149 0.6560 gm/cm 3. The compressibility index was found in the range 2.9411-13.0434%. The Hausner ratio was found in the range 1.03-1.15. The angle of repose was found in the range 22.29-28.78. The variation of results is due to different concentration of excipients with drug in each formulation. Table 7: Evaluation tests for Felodipine liquid solid compact tablets Batch Hardness (kg/m 3 ) Thickness (mm) Friability (%) Disintegration time (min) F1 4.18 3.45 0.28 19 F2 4.28 3.24 0.06 21 F3 4.35 3.44 0.11 13 F4 4.42 3.27 0.20 16 F5 4.90 3.44 0.16 17 F6 5.76 3.69 0.44 09 F7 6.48 3.05 0.18 12 Table 8: Evaluation tests for Felodipine liquid solid compact tablets Batch Weight Variation (mg) Drug Content (%) Wetting time (min) F1 460±0.2 99 1.3 F2 584±0.4 98 2.3 F3 485±0.1 100 1.4 F4 610±0.3 99 1.6 F5 430±0.5 100 2.1 F6 658±1.0 100 1.3 F7 553±1.4 99 1.4 Discussion: Tablets were prepared using direct compression technique. Since the material was free flowing, tablets were obtained of uniform weight due to uniform die fill tablets were obtained in the range with acceptable weight variations as per pharmacopoeia specifications. The Hardness of the tablets was found in the range 4.18-6.48 Kg/cm 2 The thickness of the tablets was found in the range 3.05 3.53 mother friability of tablets was observed in the range 0.06-0.44. The disintegration time was found in the range 09-23mins.The wetting time was found in the range 1.3-2.6mins. Tablets are evaluated for the content uniformity test all the formulations are under the IP specifications. Table 9: In vitro dissolution profile of different formulations in ph 6.8 phosphate buffer Time (Min) F1 F2 F3 F4 F5 F6 F7 (C.T) 0 0 0 0 0 0 0 0 10 35.62 32.41 38.14 37.26 38.27 35.13 32.08 Priyanka D et al. Int J Trends in Pharm & Life Sci. 2017: 3(4); 55-66. 62

% drug release Log % drug remeaining % of Drug Release RESEARCH ARTICLE e-issn: 2454-7867 2)0 48.16 46.17 46.31 44.25 48.26 46.40 44.21 30 57.85 61.68 62.45 60.46 65.23 61.24 59.18 40 68.70 67.09 70.73 69.13 77.45 74.07 65.37 50 79.19 78.32 85.56 78.81 88.64 82.46 79.28 60 82.45 80.17 92.14 88.05 98.36 93.24 91.38 150 100 50 Dissolution Profile f1 10 20 30 40 50 60 Time in (mins) f6 f7 Fig. 6: In-vitro Dissolution profile of Felodipine Liquisolid compact formulations F1-F7 Discussion: In vitro drug release studies were conducted for the formulation using USP dissolution apparatus type- II (paddle), at 50 rpm. The percentage drug release at the end of 60mins was found in the range 80.17-98-36%. Kinetic analysis of dissolution data Table 10: Drug Release Kinetics of Batch (F5) Liquisolid compact Time Square root of % drug Log % drug % drug Log % drug Log time (min) time released released remaining remaining 0 0-0 - 100 2 10 3.162278 1 38.27 1.5828585 61.73 1.790496277 20 4.472136 1.30103 48.26 1.6835873 51.74 1.713826424 30 5.477226 1.477121 65.23 1.8144474 34.77 1.541204691 40 6.324555 1.60206 77.45 1.8890214 22.55 1.353146546 50 7.071068 1.69897 88.64 1.9476297 11.36 1.055378331 60 7.745967 1.778151 98.36 1.9928185 1.64 0.214843848 150 10²0= 0.9443 50 0 Zero order plot 0 50 time(min) 100 Fig. 7: Zero order kinetics of optimized batch (F5) 2 1.5 1 0.5 0 First order plot R² = 0.8563 0 20 40 60 80 Time (min) Fig. 8: First order kinetics of optimized batch (F5) Priyanka D et al. Int J Trends in Pharm & Life Sci. 2017: 3(4); 55-66. 63

% drug release Log % drug release RESEARCH ARTICLE e-issn: 2454-7867 120 100 80 60 40 20 0 R² = 0.9874 Higuchi plot 0 5 10 Square root time Korsemeyer peppa's plot Priyanka D et al. Int J Trends in Pharm & Life Sci. 2017: 3(4); 55-66. 64 2 1 0 0 1 2 Log time Fig. 9: HIGUCHI model of optimized batch (F5) Fig. 10: Korsemeyer peppa s model of optimized batch (F5) Discussion: The release rate kinetic data for the F5 was given in table 9. The Optimized formulation F5 was kept in Kinetic release models; it follows Higuchi model and its regression value R2 Was 0.987 Stability results: R² = 0.9817 Table 11: Percentage Cumulative release of stability studies of optimized Studies Parameters After 15 days After 30 days After 45 days Physical appearance No change No change No change Weight variation (mg) 435.0±0.34 434.0±0.55 433.0±0.23 Thickness (mm) 3.69 3.53 3.74 Hardness (kg/cm 3 ) 5.76 5.55 5.45 Friability (%) 0.44 0.43 0.43 Drug content (%/ tablet) 100 99.81 99.0 Wetting time (min) 1.3 2 2 Disintegration time (min) 09 19.13 21.05 Percentage drug release 98.32 97.97 97.73 Discussion: According to ICH guidelines, 45 days stability study at 4 0 C ±2 0 C, 27 0 C ±2 0 C and 45 0 C ±2 0 C for 45 days at RH 75±5% of optimized formulation (F5) was carried out. It showed negligible change over time for parameters like appearance, drug content, dissolution and assay etc., No significant difference in the drug content between initial and formulations stored at 4 0 C ±2 0 C, 27 0 C ±2 0 C and 45 0 C ±2 0 C for 45 days at RH 75±5% for 45 days. CONCLUSIONS In this technique actual mechanism of increasing in solubility is the wetting of drug particle and increase in surface area of the drug due to that the solubility of drug get increased. The study shows that the solubility of Felodipine is very less in water and hence the various non-volatile solvents having more solubility than the water hence among tween-80, PEG, glycerol, propylene glycol shows more solubility of Felodipine. Hence propylene glycol is selected for the preparation of liquisolid compacts. The microcrystalline cellulose and aerosil was selected as carrier and coating material, Cros-caramellose sodium as the superdisintegrant and magnesium sterate acts as Glidant in the formulation. The evaluation of the liquisolid compacts was done pre-compression study like flow properties bulk density, tap density, angle of repose, Hausner s ratio and Carr s index was performed and shows the significant results. In post compression evaluation like size and thickness, hardness test, weight variation test, in vitro disintegration time, friability was done. The FTIR and DSC spectral studies show no interaction of drug with polymer and excipients. F5 formulation has been selected as the optimized formulation among all the other formulation and percentage drug release was 98.36 % at the end of 60 mins. Optimized formulation The Optimized formulation F5 was kept in Kinetic release models; it follows Higuchi model and its regression value R2 Was 0.987. Finally the optimized formulation.was compared with marketed formulations the results was satisfactory. Optimized formulation (F5) was kept for stability studies For 15 days, 30 days, 45 days. There is no significant difference in the values obtained before and after stability of final optimized formulation.

ACKNOWLEDGEMENT The authors wish to thank our respectful Prof. Mrs. Sumakanth, Principal, RBVRR Women s College of Pharmacy, Affiliated to Osmania University-Hyd, Barkatpura, Hyderabad, Telangana, India, for providing constant support to write this research article. REFERENCES 1. Agrawal N. Single and multiple-dose pharmacokinetics of Etoricoxib, a selective inhibitor of cyclooxygenase-2 in man. Journal of Clinical Pharmacology. 2003: 43; 268-276. 2. Ali N. The effect of type and concentration of vehicles on the dissolution rate of a poorly soluble drug from liquisolid compacts. Journal of Pharmacy & Pharmaceutical Sciences 2005: 8(1); 18-25. 3. Ansel HC. Pharmaceutical Dosage Form and Drug Delivery Systems, Tablets, New Delhi, B.i.waverly publication, eight edition 2005. 4. Aulton M E. Hand Book of pharmaceutics, modified release dosage form, London, Harcourt publishers, second edition 2002. 5. Aulton ME. Pharmaceutics: The science of dosage form design, Churchill/livingstone, English Language Book Society, third edition 1990. 6. Banker GS, Lachman L, Libermann HA. The theory and practice of Industrial Pharmacy, Tablets. Bombay Varghese Publishing house, third edition 1991. 7. Buckingham, E. On physically similar systems: Illustrations of the use of dimensional equations. Phys. Rev., 1914, 4(4):345 376. 8. Carter SJ. Cooper and Gunn s Tutorial pharmacy, Powder flow and Compaction, New Delhi CBS publishers & distributors, sixth edition 2000. 9. Chien YW. Novel drug delivery system, Oral drug delivery& delivery systems. New York Marcel dekker inc, second edition 1992, 139-140. 10. Costa P. Modeling and comparison of dissolution profiles. European Journal of Pharmaceutical Sciences. 2001; 13: 123 133. 11. Edgar B. Pharmacokinetics of Felodipine in patients with impaired renal function. British Journal of Clinical Pharmacology. 1989: 27(1); 67-74. 12. Fincher JH. Particle size of drugs and its relationship to absorption and activity. J. Pharm. Sci. 1968: 57(11); 1825-1835. 13. Fricker G. Relevance of p-glycoprotein for the enteral absorption of cyclosporin A: in vitro in vivo correlation. Br J. Pharmacol. 1996: 118; 1841 1846. 14. Gardner D. The InteliSite capsule: a new easy to use approach for assessing regional drug absorption from the gastrointestinal tract. Pharm Technol Eur. 1997: 9; 46 53. 15. Gurnasinghani ML. Indomethacin delivery from matrix controlled releases Indomethacin tablets. J. Control. Rel 1989: 8(3); 211-222. 16. Horsthuis GJB. Studies on up scaling parameters of the Gral high shear granulation process. Int J. Pharm.1993: 92(1); 143-150. 17. ICH Draft Guidelines on Validation of Analytical Procedures: Text and methodology (Q2R1), IFPMA, Switzerland, 1995. http://www.ich.org/lob/media/media417.pdf 18. ICH stability testing of new drug substances and products (Q1AR2), International Conference on Harmonization, IFPMA, Switzerland, 1995.http://www.ich.org/LOB/media/MEDIA419.pdf 19. Yadav AV. Formulation and Evaluation of Orodispersible LiquisolidCompacts of Aceclofenac. Indian J.Pharm. Educ. Res. 2010: 44(3). 20. Lakshmi PK. Preparation and comparative evaluation of liquisolid compacts and solid dispersions of Valsartan. S. J. Pharm. Sci. 2011: 4(2); 48-57. 21. Mokale V. Enhancement of solubility with formulation & in-vitro evaluation of oral nateglinide compacts by liquisolid technique advances in diabetes and metabolism.2013: 1(3); 57-64. 22. Sambasiva Rao A. Liquisolid Technology: An Overview, International Journal of Research in Pharmaceutical and Biomedical Sciences. 2011: 2(2): 409. 23. Shailesh T. Prajapati. Formulation and Evaluation of Liquisolid Compacts for Olmesartan Medoxomil Hindawi Publishing Corporation Journal of Drug Delivery. 2013, 870579, 1-9. 24. Abdul J. Formulation and evaluation of Piroxicam liquisolid compacts. International Journal of Pharmacy & Pharmaceutical Sciences. 2013: 5(1); 132. Priyanka D et al. Int J Trends in Pharm & Life Sci. 2017: 3(4); 55-66. 65

25. Kapure VJ. Dissolution Enhancement of Rosuvastatin Calcium by Liquisolid Compact Technique. Journal of Pharmaceutics. 2013: 315902, 1-9. 26. Dinesh MP. Liquisolid Technique for Enhancement of Dissolution Properties of Carvedilol. Scholars Research Library Der Pharmacia Lettre. 2010: 2(5); 412-427. 27. Kiran T. Enhancement of Dissolution Rate of Nimesulide by Liquisolid Compaction Technique. International Journal of PharmTech Research.2012: 4(3); 1294-1302. 28. Ruddick JA. = Toxicology, metabolism, and biochemistry of 1,2-propanediol. Toxicol App Pharmacol. 1972: 21; 102-111. 29. Nelien NFM.Propylene glycol pharmacokinetics and effects after intravenous infusion in humans. Ther Drug Monit.1987: 9; 225-258. 30. Bazzano G. Propanediol metabolism and its relation to lactic acid metabolism. Ann NY Acad Aci. 1965: 119; 957-973. Priyanka D et al. Int J Trends in Pharm & Life Sci. 2017: 3(4); 55-66. 66