www.wjpps.com Vol 8, Issue 5, 2019. 1559
FORMULATION AND EVALUATION OF FLOATING EFFERVESCENT TABLETS OF RAMIPRIL
1*Khan Mohd. Faarooq, 2Dr. Sharma Vimukhta and 2Umesh Atneriya
1Institute of Pharmacy, Dr. APJ Abdul Kalam University, Indore Madhya Pradesh, India.
2BM College of Pharmaceutical Education and Research.
ABSTRACT
Ramipril is antihypertensive prodrug which belongs to the category angiotensin-converting enzyme (ACE) inhibitor class. In Liver it is metabolized to ramiprilat in the liver. Ramiprilat is a potent, competitive inhibitor of ACE. This research is designed to develop a dosage form which retains in the stomach for longer time and the release of which is prolonged. Effervescent Floating tablets containing Ramipril were prepared in different batches i.e. F1 to F9 by direct compression technique using varying concentrations of different grades of polymer with Sodium bicarbonate and citric acid. Fomulation of effervescent tablets were evaluated by drug characterization and identification by Physical appearance, Melting point, FTIR which identified the purity of drug. Preformulation studies was done by preparation of calibration curve. Post compression evaluation was done by Drug content, Buoyancy lag time (BLT), Total floating time, Drug release study,in-vitro drug release. In vitro release studies of F1 to F9 formulations of Ramipril were carried out in the dissolution test apparatus (USP Type II). It is, thus concluded that effervescent floating tablet containing Ramipril (F9 formulation) gave slow and complete drug release spread over 20 hours. Thus F9 formulation was said to be optimized formulation. Stability study and others thickness, diameter,hardness, friability and weight of variation were also done. The spectrum thus obtained was compared with reference spectrum of Ramipril. The FT-IR spectra for pure drug was obtained by power diffuse reflectance on a FT-IR spectrophotometer in the wave number region of 4000-400 cm-1. The UV spectroscopy of ramipril exhibited absorbance maxima (λmax) at 231 nm in 6.8 pH buffer. The results obtained may be considered as tools for the manufacturer of standard formulation with great efficacy.
Volume 8, Issue 5, 1559-1576 Review Article ISSN 2278 – 4357
Article Received on 18 March 2019,
Revised on 08 April 2019, Accepted on 29 April 2019, DOI: 10.20959/wjpps20195-13834
*Corresponding Author Khan Mohd. Faarooq Institute of Pharmacy, Dr.
APJ Abdul Kalam
University, Indore Madhya Pradesh, India.
www.wjpps.com Vol 8, Issue 5, 2019. 1560 KEYWORDS: Ramipril, effervescent, floating, Tablet, FDDS, HPMC, formulation.
INTRODUCTION
The real challenge in the development of a controlled drug delivery system is not just to sustain the drug release but also to prolong the presence of the dosage form in the stomach or the upper small intestine until all the drug is completely released in the desired period of time. The residence of a drug delivery system in the upper part of the gastrointestinal tract (GIT) can be accomplished by several drug delivery systems, such as swelling, intragastric floating systems and expandable systems, Bioadhesive systems, high density systems, modified shape systems, delayed gastric emptying systems, and low density super porous systems, FDDS, also called hydrodynamically balanced system.
It is an effective technology to prolong the gastric residence time in order to improve the bioavailability of the drug.
This technology is suitable for drugs with an absorption window in the stomach or in the upper part of the small intestine, the drugs acting locally in the stomach and for drugs that are poorly soluble or unstable in the intestinal fluid.
FDDS have a bulk density lower that gastric fluid and thus remains buoyant in stomach for prolonged period of time without affecting gastric emptying time. The drug is released slowly, while the system is floating on the gastric contents.
They are also known as hydro dynamically balanced systems (HBS) as they are able to maintain their low density, Based on mechanisms of floating, two different technologies.
Effervescent FDDS
Non-effervescent FDDS
Fig.1 Floating pattern.
www.wjpps.com Vol 8, Issue 5, 2019. 1561 When they reach in stomach CO2 is liberated by the acidity of gastric content and is entrapped in jellified hydro colloid(In case of effervescent systems).
When the liberated gas is expelled from the dosage form it creates pores through which water can easily pass and helps in wetting of the polymers.
The CO2 generated compounds like calcium carbonate, sodium bicarbonate, citric acid/tartaric acid mixtures can be used.[1]
1.1 Advantages of Floating Drug Delivery System
The gastroretensive systems are advantageous for drugs absorbed through the stomach.
Examples: Ferrous salts, antacids.
Acidic substances like aspirin cause irritation on the stomach wall when come in contact with it. Hence HBS formulation may be useful for the administration of aspirin and other similar drugs.
Administration of prolongs release floating dosage forms, tablet or capsules, will result in dissolution of the drug in the gastric fluid. They dissolve in the gastric fluid would be available for absorption in the small intestine after emptying of the stomach contents. It is therefore expected that a drug will be fully absorbed from floating dosage forms if it remains in the solution form even at the alkaline pH of the intestine.
The gastroretensive systems are advantageous for drugs meant for local action in the stomach. Example: antacids.
When there is a vigorous intestinal movement and a short transit time as might occur in certain type of diarrhea, poor absorption is expected. Under such circumstances it may be advantageous to keep the drug in floating condition in stomach to get a relatively better response.[2]
1.2 Disadvantages of Floating Drug Delivery System
Floating system is not feasible for those drugs that have solubility or stability problem in G.I. tract.
These systems require a high level of fluid in the stomach for drug delivery to float and work efficiently-coat, water.
The drugs that are significantly absorbed through out gastrointestinal tract, which undergo significant first pass metabolism, are only desirable candidate.
Some drugs present in the floating system causes irritation to gastric mucosa.[2]
www.wjpps.com Vol 8, Issue 5, 2019. 1562 DRUG CHARACTERIZATION AND IDENTIFICATION
Physical Appearance
Physical appearance analysis of pure drug was carried out by visual inspection.
Result
Table 1: Physical appearance of Ramipril.
S.No. Physical property Standard Observed 1. Colour White to off white White
2. State Solid Solid
Melting Point
Melting point was determined by the capillary method using Thels tube. Here Thels tube filled with liquid paraffin and the capillary tube stop at one end and another end used for filling the drug by tapping. The capillary tube attached with thermometer and these assembly dipped in the Thels tube and tube put up on the burner , the rise temperature noted when drug melt in the capillary tube.
Result: The melting point range of Ramipril was found to be melting at 109-1100C.
FT-IR Spectroscopy
Determination by infrared absorption spectroscopy, the spectrum war compared with that obtained with Ramipril or with reference spectrum of Ramipril. The FT-IR spectra for pure drug was obtained by powder diffuse reflectance on a FT-IR spectrophotometer in the wave number region of 4000-400 cm-1.
Table 2: Interpretation of Ramipril.
S.No. Range Functional Group 1. 3400cm-1 -NH
2. 2900cm-1 -CH (aromatic starching) 3. 1730 cm-1 -C=O
4. 1320CM-1 -CH(aliphatic)
www.wjpps.com Vol 8, Issue 5, 2019. 1563 Fig.2: Ramipril Sample and Standard comparison.
Result
The characteristic peak was determined by FT-IR spectra, which identified the purity of drug.
If characteristics peak of sample are not similar with the reference peak, which shows the impurity of sample.
UV Spectrophotometry Analysis of Ramipril
Preparation of 6.8 pH phosphate buffer
Prepare a 0.2 M solution of potassium dihydrogen phosphate by dissolving 27.218 gm of substance in 1000 ml of distilled Water.
Prepare a 0.2 M solution of sodium hydroxide solution by dissolving 8 gm of substance in 1000 ml of distilled Water.
Take 50 ml of above prepared potassium dihydrogen phosphate solution & 22.4 ml of above prepared sodium hydroxide solution. Add both the solution & make the volume of the resultant solution 200 ml. Calibrate the solution for using pH meter & adjust the pH 6.8.
Standard solution
100 mg ramipril dissolve in 100 ml volumetric with 6.8 phosphate buffer. From these stock solutions(1000 µgml-1), sub stock solution of 100 µgml-1was prepared. For the absorption maxima the 10 µgml-1 concentration ramipril dilution observed in UV.
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Estimation of absorption Maxima of drug The identification test of the drug was done by double beam UV/Visible spectrophotometer (Shimadzu 1700) by scanning the drug in the range 200-400 nm. Scanning was done in 6.8 pH phosphate buffer stock solution.
Result: ramipril exhibited absorbance maxima (λmax) at 231 nm in 6.8 pH buffer.
PREFORMULATION STUDIES Solubility Study
Solubility may be defined as the spontaneous interaction of two or more substance to form a homogeneous molecular dispersion. The solubility of ramipril was tested in various common solvents. A definite quantity (5 mg) of drug was dissolved in 5 ml of each investigated solvent at room temperature. The solubility was observed only by the visual inspection.
Table 3: Solubility Profile of Ramipril in Aqueous and Non aqueous solvent.
S.No. Solvents Solubility 1 Dil. Water Slightly soluble
2 Methanol Soluble
3 Ethanol Soluble
4 6.8 Phosphate buffer Soluble
8.1.1 PREPARATION OF CALIBRATION CURVE
Preparation of stock solution
Stock solutions of 1000 µgml-1 were prepared by 100 mg ramipril dissolve in 100 ml volumetric with 6.8 phosphate buffer. From these stock solutions, sub stock solution of 100 µgml-1 were prepared and further diluted to get final concentrations of 10 µgml-1, 20 µgml-1, 30 µgml-1, 40 µgml-1, 50 µgml-1, 60 µgml-1 prepared standard curve of ramipril.
Standard curve preparation
These dilution were studied the overlain spectra by using an UV detection system to collect and compare spectral data at absorbance absorption maxima value. These sub stock solutions were further diluted to get the solutions range of 10-60 µgml-1 for Ramipril. Calibration curves were plotted by concentration vs. absorbance
Result: Absorption maxima of Ramipril
Absorption maxima of drug sample were found 231 nm.
www.wjpps.com Vol 8, Issue 5, 2019. 1565 Table 4: Standard Curve of Ramipril At 231 nm.
S.No. Concentration (µg/ml) Absorbance
1 10 0.308
2 20 0.644
3 30 0.985
4 40 1.302
5 50 1.610
6 60 1.952
Fig. 3: Calibration curve Concentration vs. Absorbance.
PRECOMPRESSION EVALUATION
Angle of Repose (θ)
The frictional force in loose powder or granules can be measurement by the angle of repose.
This is the maximum angle possible between the surface of a pile of powder or granules and the horizontal plane.
tan θ = h/r θ = tan-1 (h/r)
Where, the θ is the angle of repose, h = height, r = radius
The granules were allowed to flow through the funnel fixed to stand at definite height. The angle of repose was then calculated by measuring the height and radius of the heap of granules formed.
Table 5: Relationship between Angle of Repose (θ) and Flow Properties.
Angle of repose Flow properties
< 25 25 – 30 30 – 40
>40
Excellent Good Passable Very poor
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Bulk Density (G/CM3) and Tapped Density (G/CM3)
Both loose bulk density (LBD) and tapped density (TD) were determined. The accurately weighted amount of sample taken in a 25 ml measuring cylinder of Borosil measurement/recorded the volume of packing recorded and LBD and TD calculated by following:
LBD (loose bulk density) = Mass of Powder / Bulk Vol. of Packing TBD (tapped bulk density) = Mass of Powder / Tapped Vol. of Packing
Compressibility
The Compressibility Index and Hausner Ratio are measures of the propensity of a powder to be compressed. As such, they are measures of the relative importance of interparticulate interactions. In a free-flowing powder, such interactions are generally less significant, and the bulk and tapped densities will be closer in value. For poorer flowing materials, there are frequently greater interparticle interactions, and a greater difference between the bulk and tapped densities will be observed. These differences are reflected in the Compressibility Index and the Hausner Ratio.
Hausner’s ratio (HR)
H = Tapped bulk density / loose Bulk density.
Carr’s index (%)
% Carr Index = (TBD-LBD) ×100/TBD
Table 6: Grading of powders for their flow properties according to Carr’s Index.
Carr’s Index Flow 5-15
12-16 18-21 23-25 33-38
>40
Excellent Good
Fair to passable Poor
Very poor Very very poor
Result
This percent compressibility of powder mix was determined by Carr’s compressibility index.
Table shows result obtains for percentage compressibility. The percentage compressibility for all the formulations lies within range of 10.96 to 29.04 and formulation F3 and F9 showing good compressibility.
www.wjpps.com Vol 8, Issue 5, 2019. 1567 Table 7: Angle of repose, LBD, TB and Carr’s compressibility index.
Formulation code
Angle of repose (θ)
Loose bulk density gm/ml
Tapped density gm/ml
Carr’s
compressibility index
F1 290.32’ 0.475 0.542 12.36
F2 320.82’ 0.442 0.586 24.57
F3 300.37’ 0.482 0.576 16.31
F4 350.34’ 0.468 0.604 22.51
F5 340.22 0.485 0.578 16.09
F6 320.54’ 0.562 0.792 29.04
F7 300.21’ 0.82 0.921 10.96
F8 280.35’ 0.418 0.48 12.91
F9 300.36’ 0.832 0.952 12.6
FORMULATION AND POST EVALUATION 10.1 Formulation of Effervescent Floating Tablets
Method of Effervescent Floating Tablets
Effervescent Floating tablets containing Ramipril were prepared by direct compression technique using varying concentrations of different grades of polymer with Sodium bicarbonate and citric acid. All the ingredients were accurately weighed and passed through different mesh sieves accordingly. Then, except Magnesium stearate all other ingredients were blended uniformly in glass mortar. After sufficient mixing of drug as well as other components, Magnesium stearate was added, as post lubricant, and further mixed for additional 2-3 minutes. The tablets were compressed using single station hand operated tablet punching machine. The weights of the tablets were kept constant for all formulation.
Table 8.Composition of all the formulation (Yadav SK et. al., 2008).
Ingredient F1 F2 F3 F4 F5 F6 F7 F8 F9
Ramipril 10 10 10 10 10 10 10 10 10
HPMC K4M 100 --- --- 100 50 ---- 100 50 40
HPMC K100M --- 100 --- 50 100 100 --- 100 110 Carbopol 974P ---- --- 100 --- --- 50 50 50 50
MCC 100 100 100 50 50 50 50 --- ---
Sodium Bicarbonate 60 60 60 60 60 60 60 60 60
Citric Acid 30 30 30 30 30 30 30 30 30
Poly vinyl Pyrrolidine K30 10 10 10 10 10 10 10 10 10 Magnesium Stearate 10 10 10 10 10 10 10 10 10
Talc 5 5 5 5 5 5 5 5 5
Aerosil 5 5 5 5 5 5 5 5 5
Total weight (mg) 330 330 330 330 330 330 330 330 330 Note: All the quantities are in mg.
www.wjpps.com Vol 8, Issue 5, 2019. 1568 Post Compression Evaluation
General Characteristics
General appearance of tablet, its visual identity, size, shape, color of the tablet was evaluated.
Thickness
The thickness of 5 tablets was measured by Digital Caliper and average value were shown in results and expressed in mm.
Diameter
The diameter of 10 tablets was measured by Digital Caliper and average value were shown in results and expressed in mm.
Hardness
The hardness of the tablet was determined using a Monsanto Hardness tester. It is expressed in kilogram (kg).
Friability
The Friability of the tablet was determined using Roche Friabilator. It is expressed in percentage (%). 10 tablets were initially weighed (Winitial) and transferred into the friabilator.
The friabilator was operated at 25 rpm for 4 min. The tablets were weighed again (Wfinal).
The % friability was then calculated by:-
% Friability of tablets less than 1 % are considering acceptable.
Weight Variation Study
10 tablets were selected randomly from each batch and weighed individually to check for weight variation. USP limit for weight variation in case of tablets more than 324 mg is 5.0 % as following.
Table 9: Percentage deviation in average weight of tablet.
Average weight of tablet % deviation 130 mg or more
More than 130 mg and less than 324mg 324 mg and more
10 7.5 5
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Result
Table 10: Thickness, Hardness, Friability, Weight variation of tablets of different formulation F1 to F9.
Formulation Code
Thickness (mm)
Diameter (mm)
Hardness (Kg/cm2)
Friability (%)
Weight variation(mg)
F1 5.02 8.63 4.5 0.72 333
F2 5.11 8.65 4.8 0.84 335
F3 5.10 8.63 4.5 0.66 327
F4 5.12 8.64 4.5 0.73 330
F5 5.05 8.63 4.6 0.88 335
F6 5.10 8.64 4.8 0.68 338
F7 5.09 8.65 4.5 0.72 333
F8 5.11 8.64 4.6 0.66 330
F9 5.10 8.64 4.5 0.74 332
The measured hardness of tablets of each formulation ranged between 4.1 to 4.5 kg/cm2. The
% friability was less than 1% in all the formulations ensuring that the tablets were mechanically stable. All the tablets passed weight variation test as the % weight variation was within the Pharmacopoeial limits of ±5% of the weight.
Water Absorption Ratio and Wetting Time
A piece of tissue paper folded twice was placed in a Petridish containing 5ml of water. A pre weighed tablet was placed on the paper and the time for complete wetting was measured which is characterized by coloring of tablet. The wetted tablet was then weighed. Water absorption ration R was determined according to the following formula.
R = (Wa- Wb/ Wb) 100 Where, Wa = weight of tablet after absorption of water Wb= weight of tablet before absorption of water
Result
Table 11: Water absorption ratio and wetting time.
Formulation code F1 F2 F3 F4 F5 F6 F7 F8 F9
Water absorption ratio 102.2 130.5 145.8 156 153.9 155 150 149.5 145.2 Wetting time(sec) 174 165 159 152 145 143 160 155 140
Drug Content Study of Formulated Tablet of Ramipril
Ramipril content in the tablets was estimated by using UV spectrophotometric method based on the measurement of absorbance at λmax 231 nm in phosphate buffer 6.8.
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Result: Ramipril content in the tablets was estimated by using UV spectrophotometric method at λmax 231 nm in phosphate buffer 6.8. Ramipril content of the tablets are given in Table
Table 12: Drug content uniformity.
Batches Drug content uniformity (%)
F1 96.2
F2 97.02
F3 97.06
F4 98.42
F5 99.05
F6 99.02
F7 98.46
F8 98.45
F9 99.82
The Buoyancy Lag Time (BLT) and Total Floating Time
On immersion of tablets of different formulations in 0.1N HCl solution at 37±5°C, the tablets floated, and remained buoyant without disintegration, the results of the buoyancy lag time (BLT) and total floating time (TFT) were noted.
Result
The results of the buoyancy lag time (BLT) and total floating time (TFT) were shown in table
Table 13: Buoyancy Lag time (BLT) and Total Floating time (TFT).
Formulation code Buoyancy Lag time (sec) Total Floating time(hrs) F1
F2 F3 F4 F5 F6 F7 F8 F9
Fail 130 sec 131 sec 133 sec 120 sec 140 sec 102 sec 137 sec 135 sec
Fail
>12 hrs
>14 hrs
>14 hrs
>16 hrs
>18 hrs
>18 hrs
>20 hrs
>20 hrs
Buoyancy lag time (BLT) and total floating time (TFT) of different formulation were noted, where F1 fails to buoyancy because of absence of HPMC polymers, F2 BLT of 130 sec and TFT of >12 hours, F3 BLT of 131 sec and TFT of >14 hours, F4 BLT of 133 sec and TFT of
>14 hours, F5 BLT of 120 sec and TFT of >16 hours, F6 BLT of 140 sec and TFT of >18 hours, F7 BLT of 102 sec and TFT of >18 hours, F8 BLT of 137 sec and TFT of >20 hours, F9 BLT of 135 sec and TFT of >20 hours, With reference to buoyancy studies results it can
www.wjpps.com Vol 8, Issue 5, 2019. 1571 be concluded that the batch containing HPMC polymers showed good buoyancy lag time (BLT) and total floating time (TFT). Formulation F9 containing HPMC K4M, HPMC K100M and carbopol 974P showed good BLT of 135 sec and TFT of more than 20 hrs.
Drug Release Study of Formulated Tablet of Ramipril
In vitro release studies of F1 to F9 formulations and one brand of Ramipril were carried out in the dissolution test apparatus (USP Type II). The tests were carried out in 900 ml of dissolution media 6.8 pH buffers for 24 hrs at 50 rpm at 37±0.5°C 10 ml of the aliquot were withdrawn at different predetermined time intervals (0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20 hr) and filtered. The required dilutions were made with and the solution was analyzed for the drug content by using UV detector detecting at λmax 231 nm 10 ml of sample was replaced in the vessel after each withdrawal to maintain sink condition. From this percentage drug release was calculated and this was plotted against function of time to study the pattern of drug release. The in-vitro drug release profiles of tablet from each batch (F1 to F9) were studied.
The plot of cumulative percentage drug release versus time (hr) was plotted.
Result
In vitro release studies of F1 to F9 formulations of Ramipril were carried out in the dissolution test apparatus (USP Type II). The in-vitro drug release profiles of tablet from each batch (F1 to F9) were studied. The plot of cumulative percentage drug release versus time (hr) was plotted and depicted as shown in Figure.
Fig. 4: Cumulative percentage drug release versus time.
www.wjpps.com Vol 8, Issue 5, 2019. 1572 Table 14: In-vitro drug release profile of tablets of F1 to F9.
Time (hr) Cumulative Percentage Drug Release
F1 F2 F3 F4 F5 F6 F7 F8 F9
0.5 19.3 12.3 20.1 18.2 15.0 14.3 20.4 16.2 15.2 1.0 31.2 25.2 33.4 29.3 28.2 27.8 35.1 24.5 23.3 2.0 43.5 37.1 45.2 42.5 39.8 38.9 44.8 35.1 34.2 4.0 54.8 49.8 56.3 52.8 52.4 51.2 56.9 48.6 49.2 6.0 67.2 58.2 70.0 65.2 64.8 62.4 71.2 57.2 56.4 8.0 84.3 70.0 86.8 83.2 78.2 74.4 87.1 68.3 68.7 12.0 97.1 88.4 95.3 92.2 92.5 91.3 95.1 92.3 87.8 14.0 - 97.4 97.6 98.5 97.3 98.0 98.2 96.6 97.7 16.0 - - - - 98.6 98.6 98.7 98.8 99.1 18.0 - - - 99.1 99.2 99.5 99.8
20.0 - - - -
24.0 - - - -
It is, thus concluded that effervescent floating tablet containing Ramipril (F9 formulation) gave slow and complete drug release spread over 20 hours. Thus F9 formulation was said to be optimized formulation.
Fig 5.Cumulative percentage drug release versus time (F9).
Ramipril release from the effervescent floating tablets was studied in phosphate buffer pH 6.8. The release profiles of various formulations are shown in table no.7.9 figure no. 7.9 and 7.10. Formulation F1 released 97.1% of the drug in 12 hours. Formulation F2 released 97.4%
of the drug in 14 hours. Formulation F3 released 97.6% of the drug in 14 hours. Formulation F4 released 98.5% of the drug in 14 hours Formulation F5 released 98.6% of the drug in 16 hours. Formulation F6 released 99.1% of the drug in 18 hours. Formulation F7 released 99.2% of the drug in 18 hours. Formulation F8 released 99.5% of the drug in 18 hours.
www.wjpps.com Vol 8, Issue 5, 2019. 1573 Formulation F9 released 99.8% of the drug in 18 hours. Thus F9 formulation was said to be optimized formulation.
Stability Study of Formulated Tablet of Ramipril
Stability studies performed on batch F9 as per ICH guidelines for 30days at 400C±20C/75%
RH ± 5% shows no remarkable changes in the physical properties of the physical properties of the tablets as well as no remarkable changes in the drug content and the release profile as indicated in table. The studies shows tablets after stability studies are in acceptable range.
Result
Table 15: Stability study results for F9 formulation.
S.No. Parameters studied Initial After 1 month
1 Wt. variation 332 332
2 Hardness 4.5 4.3
3 % friability .74 .76
4 Floating lag time (sec) 135 136 5 Total floating time (hrs) >20 >20 6 Cum. % Drug release 99.8 99.1
SUMMERY AND CONCLUSION
A recent advance in novel drug delivery system aims to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance. One such approach is floating drug delivery system.
The present study was an attempt to develop FDDS for Ramipril, for the prevention of complications of cardiovascular disease. The main interest in such a dosage form was to avoid extensive first pass metabolism, degradation in stomach and for prolonged effect or sustained release profile.
The effervescent floating tablets of Ramipril were formulated in nine different batches F1 to F9 by using hydrophilic polymers HPMC K100M, HPMC K4M and hydrophobic polymer carbopol 974P along with effervescing agent sodium bicarbonate and citric acid. It was found that carbopol has a negative effect on floating behavior but it was used only for the drug release retardant characteristics. All the formulations were prepared by direct compression method. Addition of citric acid, to achieve buoyancy under the elevated pH of the fed stomach, caused an enhancement in drug release. Polymer swelling is crucial in determining the drug release rate and is also important for flotation. A lesser FLT and a prolonged floating
www.wjpps.com Vol 8, Issue 5, 2019. 1574 duration could be achieved by varying the amount of effervescent and using different polymer combinations. The in vitro drug release profiles obtained for tablets made with combinations of HPMC K4M, HPMC K100M, Carbopol 974P showed lesser FLT (<60 s) and a prolonged floating duration (>20hrs) with controlled and sustained release of Ramipril.
Preformulation studies were carried out. The physical appearance, melting point and FT-IR spectra of drug were found to be concordant with mentioned in BP, which identify the sample. Solubility of ramipril was determined in various aqueous and nonaqueous solvent.
Finally it can be concluded that selected drug and polymers fulfill the all parameters which can be required for the optimized effervescent floating drug delivery system. The prepared tablets of all the formulations were evaluated for physical characters like tablet hardness, friability, weight variation buoyancy lag time, total floating time, assay, in-vitro drug release.
The main aim was to optimize the formulation for 18 hours in-vitro release and total floating time to more than 20 hours.
Ramipril release from the effervescent floating tablets was studied in phosphate buffer pH 6.8. The release profiles of formulation F9 are released 99.8 % of the drug in 18 hours.
Finally it can be concluded that effervescent floating tablet containing Ramipril (F9 formulation) gave slow and complete drug release spread over 20 hours.
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