See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/275471482 Formulation and Evaluation of Tranexamic acid sustained release Tablets(IJCPS) Article · January 2015 CITATIONS READS 0 1,844 1 author: B. Venkateswara Reddy Santhiram College of Pharmacy 86 PUBLICATIONS 128 CITATIONS SEE PROFILE Some of the authors of this publication are also working on these related projects: bothmebavarine hydrochloride,repaglinide View project All content following this page was uploaded by B. Venkateswara Reddy on 27 April 2015. The user has requested enhancement of the downloaded file. B. Venkateswara Reddy, IJCPS, 2015, 3(2): 1537–1543 ISSN: 2321-3132 International Journal of Chemistry and Pharmaceutical Sciences Journal Home Page: www.pharmaresearchlibrary.com/ijcps Research Article Open Access Formulation and Evaluation of Tranexamic Acid Sustained Release Tablets B. Venkateswara Reddy*, A. Divyasri Department of Industrial Pharmacy, St.Paul’s College of Pharmacy, Turkayamjal (V), Hayathnagar (M), R.R.Dist-501510. ABSTRACT The aim of the current investigation is to design oral sustained release tablets of Tranexamic acid a drug used for the treatment or prevention of menorrhagia, haemorrhage and various bleeding disorders. The tablets were prepared by the Wet granulation method using varying concentrations of sustained release polymers HPMC, cetosteryl alcohol and Ethyl cellulose. The compatibility of the polymers was ruled out by FT-IR studies and found to be compatible. Total 11 formulations were prepared. The Tranexamic acid and the powder-blends of tablets were evaluated for their physical properties like angle of repose, bulk density and compressibility index and found to be good and satisfactory. The prepared tablets were evaluated for in process and finished product quality control tests including appearance, dimensions, weight variation, hardness, friability, drug content, and in vitro drug release. The dissolution medium used was pH 6.8. phosphate buffer. All formulations showed acceptable pharmaco-technical properties and complied with in-house specifications for tested parameters. Among all the formulations (F1-F11), F9 shows good flow properties and physicochemical characteristics of prepared tablets were found within the specification and formulation F9 has shown better drug release over 12 hours of time and it released 98.85% of drug out of 11 formulations. The mechanism of drug release from the optimized formulation follows zero order kinetics and Peppa’s plot. Keywords: Antifibrinolytic, Tranexamic acid, Sustained release, Wet granulation method, Zero order release. ARTICLE INFO CONTENTS 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1538 2. Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1538 3. Results and discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1540 4. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .1543 5. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1543 Article History: Received 21 November 2014, Accepted 18 January 2015, Published Online 27 February 2015 *Corresponding Author Dr. Basu Venkateswara Reddy Department of Industrial Pharmacy, St.Paul’s College of Pharmacy, Turkayamjal (V), Hayathnagar (M), R.R.Dist-501510. Manuscript ID: IJCPS2427 PAPER-QR CODE Citation: B. Venkateswara Reddy, et al. Formulation and Evaluation of Tranexamic Acid Sustained Release Tablets. J. Chem, Pharm, Sci., 2015, 3(2): 1537-1543. Copyright © 2015 B. Venkateswara Reddy, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. International Journal of Chemistry and Pharmaceutical Sciences 1537 B. Venkateswara Reddy, IJCPS, 2015, 3(2): 1537–1543 ISSN: 2321-3132 1. Introduction The oral route of drug administration has been the one used mostly for both conventional as well as novel drug delivery [1]. The reasons for this preference are obvious because of the ease of administration and widespread acceptance by patients. For many drugs, the basic goal of therapy is to achieve a steady-state blood or tissue level that is therapeutically effective and non-toxic for an extended period of time. Nowadays most of the pharmaceutical scientists are involved in developing an ideal DDS. This ideal system should have advantage of single dose for whole duration of the treatment and it should deliver the drug directly at specific site [2-4]. The design of oral sustain drug delivery system (DDS) should be primarily aimed to achieve the more predictability and reproducibility to control the drug release, drug concentration in the target tissue and optimization of the therapeutic effect of a drug by controlling its release in the body with lower and less frequent dose [6,7]. The design of proper dosage regimens is an important element in accomplishing this goal. The idealized objective points to the two aspects most important to drug delivery, namely, spatial placement and temporal delivery of a drug. Spatial placement relates to targeting a drug to a specific organ of tissue, while temporal delivery refers to controlling the rate of drug delivery to the target tissue [8]. An appropriately designed sustained release drug delivery system can be a major advance toward solving these two problems. Tranexamic acid formulated in an oral dosage form must contain atleast one agent that decreases tranexamic acid release in the stomach. Such formulations minimize nausea, vomiting, and other adverse gastric effects that may accompany tranexamic acid therapy. One embodiment is an extended release formulation with waxes, polymers, etc. that prevent a bolus release of tranexamic acid in the stomach. An alternative embodiment is a delayed release formulation with polymers that prevent release of tranexamic acid in the acid environment of the stomach and delay its release until the formulation reaches the less acid environment of the intestines. Such formulations enhance patient compliance with therapy because adverse effects of tranexamic acid therapy are reduced [9, 10]. Hence, in the present work an attempt will be made to formulate and evaluate tranexamic acid sustained release tablets. 2. Materials and Methods Tranexamic Acid was obtained as a gift sample from Drawin formulation Pvt.Ltd. Hydroxy propyl methyl cellulose (15cps), Ethyl cellulose, Cetostearyl alcohol, Carbomer, Cellulose Acetate Phthalate, Lactose, Magnesium Stearate and Talc were purchased from SD fine chemicals, Mumbai. Drug excipient compatibility studies by FTIR: It was carried out by taking FT-IR Infrared spectra of pure drug, and drug-polymer by KBr pellet technique and was recorded in the range of 4000–400 cm-1 using FT-IR Spectrophotometer. Formulation of sustained release tablets: All the ingredients were weighed accurately as mentioned in the table 1. Tranexamic Acid, Cetostearyl alcohol, Ethyl cellulose, Cellulose Acetate Phthalate and H.P.M.C-15cps, was passed through #40 mesh sieve &collected in a poly bag. Above sifted materials was Loaded in a planetary mixer and mixed for 15min at slow speed. Binder solution (0.5gm of Placidone S-630 was added in a 55ml of IPA) was added to the contents of planetary mixer and obtained the wet dough mass. Wet mass was dried at 50ºC-55ºC by using tray dryer for 2 to 3hr. Dried granules was passed through #16 mesh sieve and over sized granules passed through 2.0mm multi mill at medium speed in forward direction. Finally milled granules was passed through #16 mesh sieve and loaded in a double cone blender. Magnesium stearate was passed through #40 mesh and it was added to the contents of double cone blender and mixed for 10 min. Blended material was loaded in a hopper and compressed into tablets by using (cad mach) compression machine with (19/8.5mm) mm caplet shaped punches. Table 1: Composition of sustained release tablets of tranexamic acid In mg F1 F2 F3 F4 F5 F6 F7 F8 650 650 650 650 650 650 650 650 Tranexamic Acid 150 100 100 50 --50 -Ethyl cellulose --50 -100 -50 100 Cetostearyl alcohol 150 100 -100 -100 50 100 Carbomer -100 50 100 100 100 100 -HPMC k15m --100 50 100 100 50 100 Cellulose Acetate Phthalate 35 35 35 35 35 35 35 35 DCP granules Qs Qs Qs Qs Qs Qs Qs Qs IsoPropyl Alcohol 10 10 10 10 10 10 10 10 Magnesium stearate 5 5 5 5 5 5 5 5 Talc 1000 1000 1000 1000 1000 1000 1000 1000 Total weight(mg) F9 650 100 50 100 -50 35 Qs 10 5 1000 F10 650 -150 100 50 -35 Qs 10 5 1000 F11 650 100 --100 100 35 Qs 10 5 1000 Evaluation of the granules:[11,12] The prepared granules were evaluated for various precompression parameters such as bulk density, tapped International Journal of Chemistry and Pharmaceutical Sciences 1538 B. Venkateswara Reddy, IJCPS, 2015, 3(2): 1537–1543 density, angle of repose, hausner’s ratio, compressibility index to determine the flow properties of the prepared granules. Evaluation of tablets: [11, 12] The tablets were evaluated for Appearance, Weight variation, Thickness, Diameter, Hardness and Friability to meet the Pharmacopoeial standards. Determination of Weight Variation of the tablets Ten tablets were selected at random from each batch and were weighed accurately and average weights were calculated. Then the deviations of individual weights from the average weight and the standard deviation were calculated by using the formula, − ∗ = × Where, X → Actual weight of the tablet; X*→ Average weight of the tablet. Limit for weight variation is ± 10% Determination of Thickness of the tablets: Thickness of ten randomly selected tablets from each batch was measured with a Slide Calipers. Then the average thickness and standard deviation were calculated. Determination of Hardness of the tablets: Five tablets were sampled randomly from each batch and the hardness was determined by using Monsanto Hardness Tester. Then average hardness and standard deviation was calculated. Determination of Friability of the tablets: Ten tablets were sampled randomly from each batch and the friability was determined using Roche type Friabilator. A pre-weighed tablet sample was placed in Friabilator which was then operated for 100 revolutions (25 rpm). The tablets were then dusted and reweighed. Then percentage friability was calculated by using the formula, − = × Where, I→ Initial weight, F→ Final weight. Limit not more than 1% Drug content: [13,14] Three tablets were selected randomly from each batch and taken separately into three 100 ml volumetric flasks. In each flask 100 ml of Phosphate buffer pH 6.8 was poured and kept for 24 hrs. After filtering the solutions, the absorbance of the filtrate was measured at 350 nm. From these absorbance, drug content was determined and average and standard deviation was calculated Drug content = concentration × di. Factor × conversion factor × amt. of stock sol. In-vitro drug release studies: [15, 16] In-vitro dissolution study of tranexamic acid was carried out using USP Type-II (Paddle). Dissolution was carried out for first two hours in 0.1N Hcl and then in 6.8 pH phosphate buffer upto 10 hours. 5 ml samples were withdrawn at predetermined time intervals and replaced with fresh media. Samples withdrawn were analyzed by UV spectrophotometerically and the amount of drug released is calculated. Drug release kinetics for prepared sustained release tablets:[17] International Journal of Chemistry and Pharmaceutical Sciences ISSN: 2321-3132 To study the release kinetics, data obtained from in vitro release were plotted in various kinetic models. a) Zero order equation The graph was plotted as % drug release Vs time in hours. C=K0 t Where, K0 -Zero order rate constant in conc/time and T Time in hours. The graph would yield a straight line with a slope equal to K0 and intercept the origin of the axis. The results were tabulated and graph was shown. b) First order equation The graph was plotted as log cumulative % drug remaining Vs time in hours. Log C=log CO-Kt/2.303 Where, CO-Initial concentration of drug, K – First order constant and T – Time. C) Higuchi kinetics The graph was plotted as cumulative % drug release Vs square root of time Q=Kt1/2 Where, K- Constant reflecting design variable of system. (Differential rate constant), t-time in hours. Hence drug release rate is proportional to the reciprocal of square root of time. If the plot yields a straight line, and the slope is one, then the particular dosage form is considered to follow Higuchi kinetics of drug release. The results were tabulated. e) Korsmeyer – Peppas equation To evaluate the mechanism of drug release, it was further plotted in Peppas equation as log cumulative % of drug released Vs time. Mt /Mα = Ktn Log Mt /Mα = log K + n logt Where, Mt/Mα-fraction of drug released at time t, t – Release time, K – Kinetic constant (incorporating structural and geometric characteristics of Preparation) and n – Diffusional exponent indicative of the mechanism drug release. If n value is 0.5 or less, the release mechanism follows “Fickian diffusion” and higher values of 0.5<n<1 for mass transfer follow a non-Fickian model (anomalous transport). The drug release follows zero-order drug release and case II transport if the n value is 1. For the values of n higher than 1, the mechanism of drug release is regarded as super case II transport. The model is used to analyze the release of pharmaceutical polymeric dosage forms when the release mechanism is not known or more than one type of release phenomenon was involved. The n value could be obtained from slop of the plot of log cumulative % of drug released Vs log time. The results were tabulated. Stability study: After determining drug content, the tablets were charged for the accelerated stability studies according to ICH guidelines (40 ±2ºC and 75 ± 5% RH) for a period of 6 months in stability chambers. The samples were taken out at 30, 60, 90 and 180 days and evaluated for the drug content, dissolution, related substances and physical parameters like hardness and friability. 1539 B. Venkateswara Reddy, IJCPS, 2015, 3(2): 1537–1543 ISSN: 2321-3132 3. Results and Discussion Drug excipient compatibility studies by FTIR: The IR spectra of all the tested samples showed the prominent characterizing peaks of pure drug Tranexamic Acid, individual polymers, HPMC K-15M, Cetostearyl alcohol, Cellulose Acetate Phthalate, Ethyl cellulose and carbopol 940 and the admixture of drug and polymers and Figure1: IR Spectra for Pure Tranexamic acid (TA) Figure 2: IR Spectra for Hydroxy Propyl Methyl Cellulose K-15M Figure 5: IR spectra for Cetostearyl alcohol International Journal of Chemistry and Pharmaceutical Sciences was confirmed that no chemical modification of the drug has been taken place and thus they were proved to be compatible with each other and hence suitable for preparation of sustained release tablets. Figure 3: IR spectra for Carbopol 940 Figure 4: IR Spectra for Cellulose Acetate Phthalate Figure 6: IR spectra for Ethyl Cellulose 1540 B. Venkateswara Reddy, IJCPS, 2015, 3(2): 1537–1543 ISSN: 2321-3132 Evaluation of the Granules The Flow properties of the granules were evaluated for angle of repose (Flow properties) and derived properties (Bulk density, Tapped density, Carr’s index and Hausner’s ratio) and the results were tabulated in table no.2. The flow properties and other derived properties evaluated for all the 11 formulations were proved to be within limits showing good flow properties while formulation code F-9 showed very good flow properties than all the other formulations. Figure 7: IR Spectra for TA+polymers F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 Angle of Repose(Ɵ) 28.63±1.54 26.03±1.61 26.37±1.08 27.04±1.17 28.81±1.34 26.23±1.58 25.98±1.61 29.07±1.37 25.27±1.09 28.91±1.01 F11 29.34±1.81 S.No Table 2: Results for Micromeritic properties Bulk density Tapped density Carr’s Index gm/cc gm/cc 0.386±0.02 0.426±0.01 9.4±1.26 0.426±0.04 0.432±0.01 12.5±1.02 0.377±0.01 0.428±0.00 14.2±1.05 0.400±0.04 0.410±0.00 12.8±1.60 0.423±0.01 0.430±0.01 10.6±1.20 0.387±0.01 0.391±0.19 8.9±1.50 0.418±0.01 0.426±0.01 14.6±1.30 0.392±0.01 0.412±0.01 13.5±1.02 0.386±0.02 0.426±0.01 9.4±1.26 0.426±0.04 0.432±0.01 12.5±1.02 0.377±0.01 0.428±0.00 14.2±1.05 Evaluation of tablets The tablets were evaluated for Appearance, Weight variation, Thickness, Diameter, Hardness and Friability. The thickness of all tablets was found to be in the range of 3.05±0.08-3.13±0.05mm and hardness was found to be in the range of 5-6 kg/cm2 in all the formulations. In all the formulations, the % friability was 0.172±0.02 -0.260±0.02 S.No F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 below 1%. The average weight was found to be 997-998 mg which is within the given limits. Hence all the tablets were found to show less weight variation. The drug content of all formulations ranged from 97.02±0.35- 99.73±0.99% which is within the specified IP limits. Table 3: Physicochemical parameters of tablets Weight Thickness Hardness Friability Variation(mg) (mm) Kg/cm2 (%) 997±1.43 3.06±0.01 6.32±0.21 0.238±0.02 998±1.58 3.08±0.08 6.20±0.32 0.240±0.01 997±1.74 3.07±0.02 6.34±0.25 0.246±0.02 997±1.82 3.08±0.06 6.40±0.24 0.184±0.03 998±1.08 3.10±0.05 6.58±0.32 0.260±0.02 998±1.72 3.13±0.05 6.70±0.37 0.242±0.01 998±1.49 3.07±0.03 5.7±0.35 0.242±0.01 998±1.47 3.09±0.02 6.36±0.22 0.208±0.01 999±1.60 3.05±0.08 6.60±0.24 0.172±0.02 998±1.13 3.09±0.06 6.18±0.02 0.236±0.01 997±1.60 3.12±0.07 6.34±0.34 0.260±0.02 In-vitro drug release studies: For all the formulations there was no initial burst release occurred but the release was constantly in a controlled manner for a prolonged period of time up to 12 hrs. The invitro drug release values showed that the drug from all the International Journal of Chemistry and Pharmaceutical Sciences Hausner’s Ratio 1.14±0.02 1.12±0.03 0.82±0.02 0.85±0.02 0.95±0.02 0.90±0.02 1.13±0.02 1.15±0.02 1.14±0.02 1.12±0.03 0.82±0.02 Drug content (%) 98.03±0.15 98.49±0.61 99.47±0.36 98.21±0.55 97.02±0.35 98.65±0.20 98.50±0.45 99.26±0.30 99.73±0.99 97.25±0.36 98.63±0.15 formulations was released completely (very nearly 100 %) released within 12 hrs except formulation 1, 4 and 6 which showed release only up to 10 hrs and formulation 5, 10 and 11 which showed release only up to 11hr while formulation 1541 B. Venkateswara Reddy, IJCPS, 2015, 3(2): 1537–1543 code F-9 being released in a more sustained and prolonged manner showing 98.85 % drug release at the end of 12th hr. The best formulation F-9 show good flow properties and sustained and prolonged drug release. Hence taking all the results of evaluated parameters into consideration, the formulation code bearing F-9 was considered as the best formulation with very good flow properties, as well as more prolonged and sustained release of the drug. Kinetic release data Time in Hours 0 1 2 3 4 5 6 7 8 9 10 11 12 F1 0 9.53 18.26 28.52 35.45 43.26 55.63 64.28 73.45 85.34 96.58 ------- F2 0 9.02 16.23 19.65 27.02 32.43 43.21 50.63 59.71 68.24 76.62 87.23 93.52 F3 0 8.53 12.65 17.84 21.55 28.75 32.65 49.43 56.88 66.63 75.15 87.25 91.23 ISSN: 2321-3132 Dissolution of Tranexamic acid from all the formulations developed was slow and spread over 12hrs.Release followed Zero order kinetics. Release data of the tablets more obeyed Zero order, Higuchi, Peppas equation models Higuchi plots were linear indicating that the drug release from these tablets was diffusion controlled. Among all the 11 formulations (F1-F11) the F9 formulation shows better drug release. The mechanism of this formulation follows zero order and Peppa’s plot Table 4: In-vitro dissolution data Cumulative % Drug Release F4 F5 F6 F7 0 0 0 0 12.72 14.42 9.5 11.68 24.23 25.2 18.55 18.8 32.65 33.35 26.38 26.95 44.53 41.73 32.65 35.24 53.72 49.85 43.26 43.82 65.3 56.15 51.75 50.36 74.2 64.5 62.53 59.63 86.12 72.85 74.45 66.36 92.52 83.56 85.79 75.67 96.85 90.25 96.21 84.45 ---97.23 ---90.25 ---------95.9 Figure 8: comparative in vitro drug release F1-F3 Figure 10: comparative In- Vitro drug release F8-F11 Stability studies: International Journal of Chemistry and Pharmaceutical Sciences F8 0 9.24 12.74 24.26 32.65 44.53 53.78 59.26 64.39 71.5 80.62 88.53 96.75 F9 0 9.5 17.35 25.46 35.63 43.65 52.95 60.25 69.46 77.12 85.75 93.23 98.85 F 10 0 9.63 17.25 21.63 28.85 34.56 46.58 52.45 61.5 73.76 85.74 96.15 ---- F 11 0 9.86 16.23 25.36 36.32 44.53 53.63 60.36 69.35 78.62 86.15 97.75 ---- Figure 9: comparative in In- Vitro release F4-F7 The stability studies were carried out according to ICH guidelines for formulation i.e. F-9. The tablets were packed in Alu-Alu blister packing. Then tablets were stored under Accelerated stability conditions (40±2°C/75±5% RH) and the tablets were withdrawn at every one month and evaluated for tablet parameters like description, assay and dissolution. After first month the tablets showed the same results as that of initial result at conditions. After second month the tablets showed the same results as that of initial at accelerated stability condition a slight variation in assay and dissolution i.e. ±2%. After third month the tablets showed the same results as that of initial result in accelerated condition the assay and dissolution results are deviating ±4% of the initial result. After six month the tablets showed the same results as that of initial result in 1542 B. Venkateswara Reddy, IJCPS, 2015, 3(2): 1537–1543 accelerated condition the assay and dissolution results are ISSN: 2321-3132 deviating ±5% of the initial result. 4. Conclusion Tranexamic acid sustained release tablets were prepared by Wet Granulation Method by using fixed quantity of drug and mixed with various quantities of polymers like HPMC K15m, Ethyl cellulose, C.A.P, C.S.A and C.940. The among all formulations (F1-F11), F9 shows good flow properties and Physicochemical characteristics of prepared tablets were found within the specification and formulation F9 has shown better drug release over 12 hours of time and it released 98.85% of drug out of 11 formulations. The mechanism of this formulation follows zero order and Peppa’s plot and it is confirmed that super case II transport type. According to ICH guidelines stability studies were carried out for Optimized formulation F9, that were packed in Alu-Alu Blister packing and stored at Accelerated condition i.e. 40ºC± 2ºC/75±5% RH for a period of 6 months and obtained results were within the specification. Among all formulations F9 may fulfills the objective of the present study. 5. References 1. Swarbrick J, Boylan JC. Encyclopedia of Pharmaceutical Technology. 2007: pp. 369-394. 2. Brahmankar. D.M, Biopharmaceutics and pharmacokinetics, vallabh praakashan, 2007, pp. 355-360. 3. Vyas sp, khar RK “Controlled drug delivery concepts and Advances,” ed-2002, pp.155-195. 4. Sansom Lloyd N. Oral extanded- release products. In: Therapeutic Guidelines Ltd, 1999, 22: pp.8890. 5. Herbert.A. Liberman Leon Lachman and Joseph B. Schwartz; “ Pharmaceutical Dosage forms” ; Tablets Vol-3, 2nd edition, pp.201-206. 6. Jain NK. Controlled and Novel drug delivery. CBS publishers and distribution 1997: pp. 1-2. 7. Gilberts, Banker, Neil RA. Sustained release dosage forms the Theory and Practice of Industrial Pharmacy 2001; 3rd edition, pp.430-456. 8. Rudnic E. Schawartz JB. Oral solid dosage forms. Remington's Pharmaceutical Sciences. Mack Publishing Company Easton, 2000; 1965. 9. Fenton C, Scott LJ. Mebeverine hydrochloride: a review of its use in the treatment of IBS. Pubmed 2005, 19 (5): 429-44. 10. Grant S, Fitton A. Mebeverine hydrochloride. A review of its pharmacology and therapeutic potential in the treatment of IBS. Drugs 1994, 48(2): 253-73. International Journal of Chemistry and Pharmaceutical Sciences View publication stats 11. Aulton M. E., pharmaceutics: The science of Dosage form Design. 2nd ed. Livingstone. 2002, pp. 145-167. 12. Banker GS, Anderson NR.Tablets. In: Lachman L, Lieberman HA, kanig JL. The theory and practice of industrial pharmacy.3rd Ed. 1987, pp. 182-84; 296-303, 311-12. 13. Gawande Shilpa and Chandewar Anil. Formulation and evaluation of orodispersible tablet of Mebeverine hydrochloride. Der Pharmacia Lettre 2011, 3 (6):151-156. 14. Mohiuddin AQ and sharifur MR. Evaluation of Hydrophobic materials as matrices for ControlledRelease Drug Delivery. Pak J pharma Sci., 2003; 17-28. 15. B.Venkateswara Reddy, K.Navaneetha. Formulation and Evaluation of Sustain Release Tablets of Ramipril; Pharma Tutor; 2014, 2(7); 110-119 16. Manosroi, Podjanasoonthon K., Manosroi J. Stability and release of topical tranexamic acid liposome formulations. J. Cosmet. Sci. November/ December 2002, 53: 375-386. 17. M.Ravali, K.Navaneetha, B.Venkateswara Reddy, N.Karthik. Formulation and evaluation of controlled release matrix tablets of simvastatin. World Journal of Pharmaceutical Research 2014, Vol 3(4): 1706-1721. 1543
