Synthesis and Characterization of Acelofenac Sustained Release Microspheres Using Madua Rice Starch Powder for Gastro-retentive Drug Delivery System
Sumit Pundir1, Mansi Butola2*, Drishti Joshi3, Aman Sharma4
1Sidcul I.I.E Ranipur, Haridwar, 249403, 2,3Dev Bhoomi Group of Institutions, Chakrata road, navgaon, manduwala, Dehradun, Uttarakhand, 248007, 4Production department, Tirupati Medicare Ltd., Paonta sahib 173021 (Himachal
Pradesh) India
Abstract
The purpose of the study is to extract the starch through mandua rice powder and prepare the floating microsphere for targeted delivery of aceclofenac. The microspheres were prepared by using to Technique Single emulsion use polymer and drug.
According to method drug and polymers are accurately weighed and transfered to a 100 ml beaker, the mixture is then heat over hot plate at 400 temperature for 30 min, a clear gel was obtained. Then prepare a mixture of 100 ml paraffin liquid light (75 ml) and paraffin liquid heavy (25 ml) in a 500 ml beaker and keep the beaker over a hot plate in a water bath at temperature 60 °C, add the freshly prepared gel in this mixture and stirrer the mixture by using mechanical stirrer at 2200 rpm, after 15 min added 5 drops of span 80 then after 30 min add epichlorohydrin according to formula and the mixture was continuously stirrer for 5 hours.
Then the solution was stayed for 24 hours, after that we get freshly prepared floating microsphere which were filter with petroleum ether. Preformulation studies were carried out for drug and polymers. The microsphere formulations were examined for their in vitro characteristics including percentage yield, drug content, X-rd, SEM, DSC and FTIR. The % yield of batches FM1, FM6 and FM10 were found best. It was calculated that the batch no FM1, FM6 and FM10 has best entrapment efficiency.
FM1 has the best release of all the formulations, we have seen that FM1 was the best floating microspheres formulation prepared using madua rice starch powder. The FTIR, XRD, SEM and microscopic study of microspheres confirms that microspheres using madua rice can be prepared and has better compatibility and physical appearance. The dissolution study of floating microspheres of aceclofenac using madua rice shows better release of the drug. By using pharmacokinetic modeling method it was confirmed that the Makoid-Banakar and Weibull method were best fit model for the release study of the drug. Thus it was concluded , that the microspheres prepared have good gastric retention time, Microspheres of aceclofenac reduces the side effect of the drug.
Microspheres are single unit dosage forms so dose dumping can be overcome. Madua is a natural polymer so it has no side effects and can be used in the preparation of microspheres.
Keywords: madua rice, gastro-retentive, microspheres, petroleum ether, acelofenac
Introduction
Oral administration is most versatile convenient or commonly employed route of drug delivery for systemic action. Indeed to control release system, various pharmaceutical products in different dosage form. [1] Now day most of the pharmaceutical scientist is involved in developing ideal drug delivery system (DDS) [1, 3]. This ideal system should have advantage of single dosage from for whole duration of the treatment and it should deliver the drug directly in specific site. [1]
Scientists have succeeded to develop a system that can be as near to an ideal system and it encourages the scientists to develop controlled release system [1, 4].
Oral controlled release (CR) dosage forms (DFs) is developing over the past there decades due to their considerable therapeutic advantages such as comfort of direction persistent submission or rigidity in construction [2, 4]. However this approach is bailed with some biological problems such equally failure to contain and trace the measured drug transport system indoors the looked-for state of the stomach tract (GIT) due to adjustable gastric clearing and motility [2,4] The design of oral sustain drug delivery system should be primarily expected toward complete more predictableness then reproducibility to controller the drug publication, drug concentration in the
target tissue and optimization of therapeutic effect of a drug by controlling its release in the body with lower and less frequent dose[1,5]. Conventional drug therapy typically involves the periodic dosing from a therapeutic agent that has been formulated in a manner to ensure this stability, activity and bioavailability [1, 2]
For most of the drugs, conventional method of formulation is quite effective.[2,4] However some drugs are unstable and toxic and this is a narrow therapeutic range, exhibit extreme solubility problems required localization to particular site in the body and require strict compliance or long-term use. In such cases a method of continuous administration of drug is desirable to maintain fixed plasma drug levels. [5] Hence towards overwhelmed such as difficulties gastro absorbent drug transport systems are calculated near delay the gastric preservation period of the medicines which stand close by on the go in the gastrointestinal. [2, 4] This stand unhinged in the stomach atmosphere. Take a contracted concentration window. Devise to short solubility by the in height pH area countless methods take been projected to growth the intestinal habitation if the drug transport that contains fluctuating drug distribution organization (FDDS),the mucoadhesion before bio connection arrangement, in height concentration system and extension system, hypnotic system, fabulous porous hydrogel, amount developing arrangement then floating ion interchange kauri gum. [1, 9] Microspheres be situated major circular units, with thicknesses in the micrometer range (typically 1 μm to 1000 μm (1 mm)). Microspheres are sometimes referred to as micro particles. [7] However, microsphere is different from microcapsules for the latter one has a distinct outer layer which lead to a different release dynamic process. Generally in pharmaceutics industry, microspheres can be applied to encapsulate drugs, in order to attain sustained-release, protect sensible drugs or special delivery methods, etc. [9, 10]
Gastro retentive microspheres as sustained release microspheres
Gastro retentive tablets are the dosage form which stay in the stomach for a long time and release the drug in controlled and sustained manner. It prolong the gastric residence time of the drug.[7.11] After oral administration these type of formulation retain in the stomach and releases the drug in sustained manner, so that the drug continuously exposed to upper GIT.
Bioavailability of the drug can be improved by this method, decrease the wastage of drug and improve the solubility of the drug in high pH. [2, 9]
Microspheres formulation
Microspheres are small particle, have diameters in the micrometer range (1 to 1000 um) having proteins or synthetic polymers, [1, 16] these are biodegradable in nature. That is a significant arrival in delivering physician substance to the target site in sustained and controlled release vogue. Glass microspheres, polymer microspheres and ceramic microspheres are commercially existing. [19, 21] Solid and hollow microspheres differ widely in density, hollow microspheres are used as additives to lower the density of a material. Solid microspheres have separate application depending on what matter they are fabricate of and what size they are. [11, 12] Proteins ligands adsorb onto polystyrene light and constantly, polyethylene microspheres are used as constantly or mutable filter. High sphericity of these microspheres, as well as ease of use of chromatic and fluorescent microspheres, design them highly charming from current hallucination and molten flow analysis, microscopy techniques, soundness sciences are processes trouble shooting.
Electric polyethylene microspheres are used in electronic paper digital dissert. [15, 16] Glass
prolonged therapeutic effect, diminished the GI toxic effect and dosing reprint and improve they patient concordance. [5, 7] They are floating microspheres beneficially alter they are absorption of the drug. This will enhance its bioavailability. They are prolong dosing interval which are would allow are development of the once the day formulation and thereby increase compliance beyond the level of the existing dosage forms by achieving control over gastric residence time. [8, 11]
Aceclofenac comes under the category of NSAIDs that inhibits the both enzymes cox1 and cox 2. These enzymes are responsible for the production of the inflammatory mediators in response to inflammatory stimuli. Aceclofenac is more selective towards cox 2 as compared to cox 1. This promotes gastric tolerance compared to other NSAIDs.[11,12,13] Aceclofenac mainly inhibit the production of prostaglandins (PEG2) but it also inhibits the synthesis of the interleukins and cytokines and tumor necrosis factor (TNF). Aceclofenac also affect the cell adhesion molecules from neutrophils (A19763). Aceclofenac also target the synthesis of glycosaminoglycan and mediates chronodroprotective effect.
Materials and method Material
Aceclofenac was obtained from (Shivalik Remedies Pvt. Ltd, Bhagwanpur, Roorkee, Uttarakhand,India) as a gift sample,madua rice is obtained from marketed rice powder, Calcium chloride was purchased from (Loba ChemiePvt. Ltd., Mumbai, Maharashtra, India), Epichlorohydrin was purchased from (Sisco Research Laboratories Pvt. Ltd), Sodium Bicarbonate (LobaChemiePvt. Ltd., Mumbai, Maharashtra, India), Paraffin Liquid Heavy was purchsed from (Merck Specialities Pvt. Ltd), Paraffin Liquid Light (Merck Specialities Pvt. Ltd), Sodium Bicarbonate (As a laboratories Grade).
Preformulation studies of drug Determination of melting point
As explained in B.P. (2009), melting point of Aceclofenac was determined by capillary method.
The drug was filled in a capillary tube which was sealed at one end. The tube was placed in the melting point apparatus and the required temperature to melt the drug was noted. This experiment was repeated in the triplicate and average was noted.[15,17]
Determination of functional groups by FTIR
The FTIR is used to detect the structure of the drug by placing the sample on the FTIR. It determines the structure by detecting the functional group present in the sample.[20,22]
Determination of solubility of drug in different media
The solubility study of Aceclofenac was carried out in distilled water, 0.1 N HCl and pH 7.4 phosphate buffer solution. A saturated solution of drug was prepared in 10 ml media in conical flask and was kept at mechanical shaker for 24 hrs by followed filtration of solution. Supernatant was filtered, suitably diluted and is absorbance was recorded at predetermined λmax. [23,24]
Determination of drug-excipients compatibility studies
The drugs polymers were mixed physically in 1:1 ratio and the mixtures were place in sealed phial for 1 months at a room temperature. The pure drug and material combination on drug and excipients were check by FTIR.[25,27]
Powder X-ray diffraction studies
Powder X-ray diffraction (XRD) patterns of drug and polymer were obtained using (D8- Advance, Bruker, 2008,) and the voltage 40 KV and the current 30 MA. All sample were measured in the 2θ angles between 5.00 and 30.0 with a scanning rate of 1-/ min and a step size of 0.029. [28,29]
Preparation of Madua Rice Starch Powder
Pre-gelatinized Madua starch powder is prepared using the method of Odeku et al. (2008).
Briefly, rice powder slurry in aqueous media (20% w/v) will be heated over a water bath with continuous stirring for 15 min until a clear paste is formed. Pre-formulation studies shall be carried out to determine the ability of pre-gelatinized rice starch powder. Firstly weigh 50 gm.
madua rice powder and transfer to 400 ml distilled water in a 500 ml beaker and maintain the pH by NaoH. Properly mix through mechanical stirrer at 300 rpm for 1 hours and keep the solution for 24 hours. After 24 hours the solution are centrifuge by refrigeration centrifuge apparatus at 5000 rpm at 30°C for 20 min. then separate the material, take it in a separate beaker and the obtained product is mixed with 400 ml of 2 % solution of sodium chloride. The mixture is stored in refrigerator at 48 hours. After 48 hours the mixture again centrifuge through refrigerator centrifuge apparatus at 5000 rpm or 30°C for 20 min and the obtained material was mixed in 400 ml 1 % sodium chloride solution and stored in refrigerator in 24 hours. Again the mixture was centrifuge by refrigeration centrifuge apparatus at 5000 rpm or 30° C at 20 min or prepares 80 % solution of ethanol or mixed to obtained Product and the mixture was bowling with hot plate the temperature is maintained 80°C at 1 hours. And the mixture was stored in refrigerator at 1 hour or the mixture was centrifuge by refrigeration centrifuge apparatus at 5000 rpm or 30o C at 20 min and the separate product are collected in petri plate or the material dried with hot air oven at 600 C after dried powder stored in air tided container.
Preparation of Aceclofenac Floating microspheres
The microspheres shall be prepared from a blend of freshly pre-gelatinized starch powder, drug and sodium bicarbonate at a total polymer and other reagents concentration is used according to the method are given in table 1. The microspheres were prepared by using to Technique Single emulsion use polymer and drug. According to method drug and polymers are accurately weighed and transfered to a 100 ml beaker, the mixture is then heat over hot plate at 400 temperature for 30 min, a clear gel was obtained. Then prepare a mixture of 100 ml paraffin liquid light (75 ml) and paraffin liquid heavy (25 ml) in a 500 ml beaker and keep the beaker over a hot plate in a water bath at temperature 60 °C, add the freshly prepared gel in this mixture and stirrer the mixture by using mechanical stirrer at 2200 rpm, after 15 min added 5 drops of span 80 then after 30 min add epichlorohydrin according to formula and the mixture was continuously stirrer for 5 hours. Then the solution was stayed for 24 hours, after that we get freshly prepared floating microsphere which were filter with petroleum ether.
Table.1 (Method of Preparation for Floating Microspheres Formulation)
S.No Drug Sodium Epichloro Starch Starch Buffe Buffer Wate
d (gm) (ml) ) (ml)
FM1 FM2 FM3 FM4 FM5 FM6 FM7 FM8 FM9 FM1
0
250 250 250 250 250 250 250 250 250 250
400 400 400 400 400 400 400 400 400 400
3 5 1 3 3 3 5 1 3 3
- 2 2 - - 2 2 2 - -
2 - - 2 2 - - - 2 2
- - - - 20
- 20
- - 20
20 - - - - 20
- - - -
- 20 20 20 - - - 20 20 -
Evaluation / characterization of gastro retentive microspheres Determination of percentage yield
The percentage yield is ascertained by two compounds. The disparity between the theoretical yield and the actual yield can be ascertained utilizing the percentage yield, which utilizes this formula.[31,32]
% yield = Actual yield / Theoretical yield ×100 Determination of drug content
The drug content was determined by using UV spectrophotometer. 200 mg microspheres were dissolved is 50 ml 0.1N HCL are in certainly analyzed at 273.0nm. These experiments were done is triplicate are. [33, 34]
Drug content = weight of drug in solid dispersion / weight of solid dispersion / weight of solid dispersion × 100
Determination of surface morphology
The surface morphology was determined by using SEM (scanning electron microscopic). SEM (LEO-435BF) photographs were obtained for checking the surface morphology of microspheres.
Microspheres were if clean upon double- sided cone of a cooper stump, what were coated with the gold by a boom coater. These sample were grace using a 15 KV electron shaft.[35,36]
Powder X-ray diffraction studies
Powder X-ray diffraction (XRD) patterns of drug and polymer were obtained using (D8- Advance, Bruker, 2008,) and the voltage 40 KV and the current 30 MA. All sample were measured in the 2θ angles between 5.00 and 30.0 with a scanning rate of 1-/ min and a step size of 0.029. [37,38]
Method for In-vitro dissolution study
The release rate of the floating microsphere of Aceclofenac shall be determined using United States Pharmacopoeia (USP) dissolution testing apparatus II (paddle method). The dissolution test will be performed using 900 ml of 0.1 N HCl, at 37±0.5oCand 50 rpm. A 5 ml sample shall be withdrawn from the dissolution apparatus at every time interval of 5 min and sink condition will be maintained. The samples shall be filtered through a membrane filter and dilute to suitable concentration with 0.01 N HCl. Absorbance of these sample was measured in UV spectrophotometer at 273 nm. The % drug release shall be plotted against time of determine the release profile. All the studies shall be performed three times in the study. [39,40]
In-vitro drug release kinetic studies
In order to study the exact mechanism of the drug release from the floating microspheres, drug release data shall be analyzed according to zero order, first order, Korsemeyer Poppas model, Higuchi square root model and Hixson-Crowell model. The criterion for selecting the most appropriate model shall be chosen on the basis of goodness of it test. The data shall be processed for regression analyzed using MS Excel statistical function.[41,42]
Mechanism of drug release and drug release kinetics
To analyze are mechanism of drug release, the release of data were decorated of the following kinetic models are selected as given Higuhi Kinetics Model, Korsmeyer-Pappas Kinetics Model, Hixson-Crowell Kinetics Model, Hopfenberg Kinetics Model, Makoid-Banakar Kinetics Model, Pappas-Sahlin Kinetics Model, Quadratics Kinetics Model, Weibull Kinetics Model.[43,44]
Result
Characterization Profile of drug Physical Appearance
Aceclofenac is white fine crystalline stable powder.
Solubility
Acelofenac was found practically insoluble in water, readily soluble in organic solvents like acetone, benzene, and chloroform and very soluble in alcohol.
Determination of melting point
The melting point of drug was determined by capillary method. The melting point is characteristics of any crystalline drug and is used for identification of drug. The observed melting point of drug was found to be 150oC. The indirect melting point was 149-153oC major by. The melting point thus procured was identical to the indirect value. From the result from determination of melting point, the drug was identified as Aceclofenac.
X-ray powder diffraction (X-RD) Characterization of Aceclofenac
Figure.1 X-RD of Aceclofenac
Fourier transform infrared (FTIR) spectroscopy analysis of Aceclofenac
The infrared spectrometric analysis of Acelofenac show intense band was performed from 1715.88 cm-1, 1619cm-1 and 1241.26 cm-1 corresponding to the functional group C=O, COOH, NH and OH bonding. The IR graphs are given below.
Figure.2 (FTIR of Aceclofenac as in IP 2010)
Figure.3 (FTIR spectra of Aceclofenac)
Characterization profile of Madua rice polymer Physical appearance of Madua rice starch
Madua rice powder is oval and round shape and reddish brown color. Temperature is 11-270C and soil with pH ranging from 5 to 7. It is poor flow powder, chemical test for starch is to add iodine solution red and see if it turns blue and black in colour.
Solubility of Madua Rice Powder
Madua rice powder is highly soluble in both hot and cool water.
Characterization Profile of Floating Microsphere Formulation FTIR Characterization of Floating Microsphere Formulation
Through the FTIR, the formulation of Floating Microsphere is characterized by the Cary 630, Agilent. In the FTIR graph, the attendances of the drug or used polymers are exposed by the peak of the compound
Figure.4 FTIR Characterization of Floating Microsphere Formulation-1 Percentage Yield and Entrapment Efficiency of Floating Microsphere
The percentage yield obtained in each formulation of floating microsphere after dry to all formulation is as follows.
The drug entrapment of floating microsphere is calculated in the 1.2 pH HCL solution and analyzed for Aceclofenac content by a UV spectrophotometer at the λ max value of 273 nm.
Table.2 Percentage Yield and entrapment efficiency of Floating Microspheres Batch no. % Yield Entrapment efficiency
FM 1 85.6 74.33
FM 2 79.5 58.61
FM 3 83.2 72.68
FM 4 85.9 72.82
FM 5 87.2 65.79
FM 6 74.8 74.12
FM 7 94.2 64.95
FM 8 84.6 62.53
FM 9 83.4 77.35
FM 10 80.5 72.28
Figure.5 Graphically Representation of Percentage Yield and entrapment efficiency Drug Release Profile of Formulated Floating Microsphere Formulation
The drug release of floating microspheres formulation is done in different medium (Buffer 7.4 pH, 1.2 pH HCL solution and water) and there are observed the effect of incorporated factor in the preparation of floating microspheres. We observed the release effect of water, 0.2M buffer, and 6.8 pH buffer or change the madua rice starch (Alkaloids and Pregelatinized) used to the floating microsphere. All formulation drug release percentage results are show in to the figures.
Figure 13and 14 represent the drug percentage release profile of floating microspheres formulations in water, figure 15 and 16 represent the drug percentage release profile of floating microspheres formulations in 7.4 pH buffer, figure 17 and 18 represent the drug percentage release profile of floating microspheres formulations in 1.2 pH HCL solution.
Figure.6 (a) % Release of drug in Formulations 1-5 in Water
Figure.6 (b) % Release of drug in Formulations 6-10 in Water)
Figure.7 (a)% Release of drug in Formulations 1-5 in 7.4 pH Buffer)
Figure. 7 (b)% Release of drug in Formulations 6-10 in 7.4 pH Buffer)
Figure.8 (a)%Release of drug in Formulations 1-5 in 1.2 pH HCL)
Figure.8 (b) % Release of drug in Formulations 6-10 in 1.2 pH HCL)
SEM (Scanning Electron Microscopy) Characterization of Floating Microsphere Formulation
Floating Microspheres were mounted on the brass strubs with the help of graphite glue and coated with gold under vacuum and analyzed using an electron voltage 15 KV and visualized at varying magnification range 500x, 1000x.
Figure.9 (SEM (Scanning Electron Microscopy) of Floating Microsphere FM- 1)
X-RD (X-ray Diffraction) Characterization of Floating Microsphere Formulation
Figure.10 (X-RD Plot Characterization of Formulation-1)
models define medication dissolution from instant or modified release dosage forms. There are several models to represent the drug dissolution profile where it is a meaning of t (time) connected to the quantity of drug dissolved from the medicinal dosage system. The quantitative interpretation of the value obtained in the dissolution assay is facilitated by the usage of a generic equation that mathematically translates the dissolution curve in the function of some other parameters related to the pharmaceutical dosage forms.
We are calculating the different type of kinetics models to known around the diverse kinds of drug kinetics of behavior of the drug some kinetics models name given a below, Higuhi Kinetics Model, Korsmeyer-Pappas Kinetics Model, Hixson-Crowell Kinetics Model, Hopfenberg Kinetics Model, Makoid-Banakar Kinetics Model, Pappas-Sahlin Kinetics Model, Quadratics Kinetics Model, Weibull Kinetics Model.
The calculation of kinetics model is done in the different dissolution media such as water, 0.1N HCL solution and 7.4 pH phosphate buffer solution and calculate the model with the help of DD Solver software. The model report is show in Table 3,4,5,6,7,8 and T25, T50, T75 value in Table 9 or the best fitted value in Table 10,
S.No Table.3 (Dissolution Kinetics Modelling in 0.1 N HCL Solution) Zero order First order Higuchi Korsmeyer-psppas
K0 R2 K1 R2 KH R2 n R2 KKp
FM1 0.168 0.8417 0.003 0.7802 3.001 0.4571 0.270 0.9044 10.412 FM 2 0.114 0.3103 0.001 0.0025 2.001 0.7549 0.356 0.8498 4.390 FM 3 0.005 0.2882 0.001 0.9554 0.905 0.4248 0.1262 0.9782 3.261 FM 4 0.093 0.1436 0.001 0.1502 1.666 0.8290 0.382 0.8895 3.163 FM 5 0.054 0.0001 0.001 0.1528 0.953 0.9442 0.398 0. 8196 1.653 FM 6 0.168 0.5816 0.003 0.8378 0.0890 0.9793 0.513 0.9797 2.695 FM 7 0.120 0.5217 0.002 0.0240 0.184 0.8475 0.347 0.9810 4.923 FM 8 0.100 0.3543 0.001 0.5510 0.742 0.9755 0.452 0.9833 2.265 FM 9 0.203 0.6309 0.004 0.3292 0.620 0.8330 0.339 0.9844 8.680 FM 10 0.202 0.4703 0.004 0.4118 3.595 0.8641 0.350 0.9901 8.095
S.No Table.4 (Dissolution kinetics modeling in 0.1N HCL solution)
Hixson-corwell Makoid-Banakar Quadratic Weibull
KHC R2 N R2 K1 K2 R2 α β R2
FM1 0.000 1.0859 0.066 0.9864 0.000 0.003 0.2913 69.359 1.611 0.9868 FM 2 0.000 0.0918 0.002 0.9844 0.000 0.002 0.2607 94.002 1.914 0.9457 FM 3 0.000 2.0642 0.247 0.9787 0.000 0.001 0.0272 39.039 0.316 0.9813 FM 4 0.000 0.0575 0.775 0.9716 0.000 0.002 0.8519 24.246 0.367 0.2928 FM 5 0.000 0.1037 0.424 0.9897 0.000 0.001 0.1782 76.065 0.452 0.9903 FM 6 0.001 0.7765 0.441 0.9814 0.000 0.003 0.8932 42.298 0.961 0.9897 FM 7 0.000 0.1764 0.426 0.9865 0.000 0.003 0.6351 21.913 0.398 0.9846
FM 8 0.001 0.4916 0.290 0.9973 0.000 0.002 0.7673 28.616 0.782 0.9948 FM 9 0.001 0.919 0.285 0.9925 0.000 0.004 0.5069 63.327 0.964 0.9959 FM 10 0.000 0.1885 0.351 0.9901 0.000 0.004 0.5703 23.408 0.354 0.9886
S.No Table.5 (Dissolution Kinetics Modelling in 7.4 buffer Solution)
Zero order First order Higuchi Korsmeyer-psppas
K0 R2 K1 R2 KH R2 n R2 KKp
FM1 0.192 0.8797 0.004 0.4823 3.463 0.5227 0.275 0.9731 11.687 FM 2 0.106 0.0649 0.001 0.1084 1.980 0.2392 0.128 0.8948 14.541 FM 3 0.054 0.5482 0.001 0.3889 1.009 0.8710 0.110 0.9127 8.148 FM 4 0.101 0.7390 0.001 0.3314 1.867 0.1404 0.189 0.8846 10.460 FM 5 0.020 0.9527 0.001 0.1800 1.297 0.3437 0.208 0.9806 6.156 FM 6 0.195 0.3956 0.004 0.4434 3.465 0.8715 0.358 0.9793 7.465 FM 7 0.138 0.4667 0.002 0.8503 2.525 0.1979 0.215 0.9721 11.710 FM 8 0.116 0.7814 0.002 0.9149 2.130 0.1815 0.175 0.9730 12.214 FM 9 0.177 0.5733 0.002 0.6262 3.218 0.3531 0.254 0.9881 12.120 FM10 0.188 0.4422 0.003 0.2385 3.334 0.6490 0.293 0.9891 10.353
S.No Table.6 (Dissolution kinetics modeling in 7.4 buffer solution)
Hixson-corwell MakoidBanakar Quadratic Weibull
KHC R2 N R2 K1 K2 R2 α β R2
FM1 0.000 0.8630 0.186 0.9873 0.000 0.004 0.0493 51.716 0.634 0.9834 FM 2 0.000 0.0656 0.040 0.9709 0.000 0.003 0.3792 91.697 0.544 0.9721 FM 3 0.000 0.1671 0.036 0.9884 0.000 0.001 0.6170 71.478 0.390 0.9878 FM 4 0.000 0.7892 0.215 0.8896 0.000 0.002 0.8339 8.820 0.195 0.8883 FM 5 0.000 0.4321 0.218 0.9809 0.000 0.002 0.9417 18.205 0.247 0.9822 FM 6 0.001 0.2313 0.419 0.9823 0.000 0.004 0.5913 31.613 0.575 0.9860 FM 7 0.000 0.3412 0.157 0.9826 0.000 0.003 0.9436 19.982 0.397 0.9917 FM 8 0.001 0.5700 0.090 0.9960 0.000 0.003 0.5287 31.170 0.421 0.9942 FM 9 0.001 0.4754 0.239 0.9885 0.000 0.004 0.2157 11.539 0.322 0.9838 FM 10 0.000 0.5683 0.026 0.9962 0.000 0.004 0.1578 34.090 0.5670 0.9953
S.No Table.7 (Dissolution Kinetics Modelling in water)
Zero order First order Higuchi Korsmeyer-psppas
K0 R2 K1 R2 KH R2 n R2 KKp
FM1 0.215 0.5399 0.005 0.0376 3.887 0.6113 0.289 0.9692 12.136
FM 2 0.125 0.16004 0.002 12.7113 2.315 4.5983 0.114 0.6928 18.223 FM 3 0.058 0.1766 0.001 7.3876 1.068 1.7326 0.155 0.7397 6.7910 FM 4 0.111 0.0843 0.001 5.5218 2.044 1.1920 0.174 0.8613 11.774
FM 5 0.059 0.2575 0.001 0.0835 1.043 0.8531 0.366 0.9398 2.157
FM 6 0.181 0.9295 0.003 0.5726 3.265 0.5190 0.274 0.9771 11.050 FM 7 0.159 0.4085 0.003 3.2477 2.910 0.5029 0.200 0.9730 14.577
FM 8 0.134 0.4935 0.002 0.0489 2.376 0.8495 0.348 0.9779 5.402
FM 9 0.197 0.887 0.004 0.1542 3.520 0.7713 0.322 0.9806 9.237
FM10 0.185 0.9612 0.003 0.0538 3.303 0.7198 0.314 0.9497 9.042
S.No Table.8 (Dissolution Kinetics Modelling in water)
Zero order First order Higuchi Korsmeyer-psppas
K0 R2 K1 R2 KH R2 n R2 KKp
FM1 0.215 0.5399 0.005 0.0376 3.887 0.6113 0.289 0.9692 12.136
FM 2 0.125 0.16004 0.002 12.7113 2.315 4.5983 0.114 0.6928 18.223 FM 3 0.058 0.1766 0.001 7.3876 1.068 1.7326 0.155 0.7397 6.7910 FM 4 0.111 0.0843 0.001 5.5218 2.044 1.1920 0.174 0.8613 11.774
FM 5 0.059 0.2575 0.001 0.0835 1.043 0.8531 0.366 0.9398 2.157
FM 6 0.181 0.9295 0.003 0.5726 3.265 0.5190 0.274 0.9771 11.050 FM 7 0.159 0.4085 0.003 3.2477 2.910 0.5029 0.200 0.9730 14.577
FM 8 0.134 0.4935 0.002 0.0489 2.376 0.8495 0.348 0.9779 5.402
FM 9 0.197 0.887 0.004 0.1542 3.520 0.7713 0.322 0.9806 9.237
FM10 0.185 0.9612 0.003 0.0538 3.303 0.7198 0.314 0.9497 9.042
S.NO Table.9 (Value of T50 in Zero Order, First Order in Dissolution Medium) T50 Value in Water T50 Value in 1.2 pH HCL 50 Value in 7.4 pH BUFFER Zero order First
order
Zero order First order Zero order First order
FM 1 232.473 149.594 298.149 254.762 260.272 195.492
FM 2 401.421 392.156 437.353 462.425 470.299 487.916
FM 3 860.360 1040.058 1001.817 1237.255 1127.589 2454.655
FM 4 448.814 463.465 535.279 586.881 496.207 524.003
FM 5 844.793 1028.419 925.257 1137.139 718.301 838.583
FM 6 276.522 217.583 298.00 269.192 256.956 194.481
FM 7 314.819 268.754 415.437 420.823 362.014 339.809
FM 8 373.728 364.714 499.013 549.497 432.407 436.765
FM 9 253.821 189.238 245.944 179.708 282.179 223.585
FM 10 269.801 216.318 247.509 181.627 265.522 204.841
Table.10 (Best Fitted Kinetics Model in Buffer, HCl and Water)
DSC study: - S.No
Best Fitted Kinetics Model in Buffer, HCl and Water Best Fitted Model
Water Buffer 7.4 pH 1.2 pH HCL
FM 1 FM 2 FM 3 FM 4 FM 5 FM 6 FM 7 FM 8 FM 9 FM 10
Makoid-Banakar Makoid-Banakar Makoid-Banakar Makoid-Banakar
Weibull Weibull Weibull Weibull Weibull Weibull
Makoid-Banakar Weibull Makoid-Banakar Makoid-Banakar Makoid-Banakar
Weibull Weibull Weibull Makoid-Banakar Makoid-Banakar
Weibull Makoid-Banakar
Weibull Makoid-Banakar
Weibull Weibull Makoid-Banakar Makoid-Banakar
Weibull Makoid-Banakar
The DSC data provided information about the physical properties of the drug that it is crystalline of amorphous in nature. Also it demonstrates a possible interaction between drug and polymers in the formulation. According to the DSC of aceclofenac it showed a sharp endothermic peak at 158.30 C corresponding to the melting point of the drug in the crystalline form.
Discussion
: -
• Floating microspheres of aceclofenac using madua rice was prepared and evaluated for various parameters. Different physicochemical parameters of the drug were also evaluated. Aceclofenac was a white fine crystalline powder with characteristic odor. The melting point of the drug was found to be 150 ° C. The solubility of drug was in organic solvents like acetone, benzene and chloroform.
• The FTIR and XRD study of drug was also carried out. Physicochemical study of madua rice was also performed. It was found that the madua has oval round shape and brown in colour.
• The presence of starch was confirmed by adding iodine solution which gave blue colour.
• Madua rice is highly soluble in water. It was found that madua rice has poor flow properties when compared with the potato starch.
• The FTIR, DSC and XRD was also performed for the madua rice starch powder. After Preformulation study of both drug and madua rice the floating microspheres were prepared using their different concentration. Then microspheres were evaluated for different parameters. The % yield of microspheres were calculated. Then entrapment efficiency was calculated. Then dissolution of microspheres were performed using water, 1.2 N HCl and 7.4 pH buffer solution. Their % release was calculated.
• Then the pharmacokinetic modeling of drug release for microspheres were performed and best fit model for the all microspheres were identified.
• FTIR, SEM, DSC, XRD and microscopy was also performed for all the prepared
Conclusion: -
In this present research work floating microspheres of acelofenac using Madua rice polymer were prepared and evaluated for various parameters like Percentage Yield, entrapment efficiency surface morphology, X-RD, FTIR, drug release profile and pharmacokinetics modeling. The microspheres were passed for all the tests and it was observed that floating microspheres of acelofenac can be prepared using Madua rice and is good for preparation of floating microspheres. The FTIR, XRD, SEM and microscopic study of microspheres confirms that microspheres using madua rice can be prepared and has better compatibility and physical appearance. The dissolution study of floating microspheres of aceclofenac using madua rice shows better release of the drug. By using pharmacokinetic modeling method it was confirmed that the Makoid-Banakar and Weibull method were best fit model for the release study of the drug.
The % yield of batches FM1, FM6 and FM10 were found best. It was calculated that the batch no FM1, FM6 and FM10 has best entrapment efficiency. FM1 has the best release of all the formulations, we have seen that FM1 was the best floating microspheres formulation prepared using madua rice starch powder. In this study it was concluded that the preparations which were prepared in 6.8 pH buffer were best for the preparation of floating microspheres.
References:-
1. Garg SK, Mruthunjaya K, Kumar V et al. formulation and evaluation of gastroretentive floating tablet of aceclofenace. International journal of research in pharmacy and sciences; (2011) Jun; 1(1), 66-75.
2. Reddy AB, Rani BS, Tony DE, Raja DS, Kumar NS. Aceclofenace floating tablet- A promising sustained release dosage from. International Journal of drug development and research; (2011) Jun, 3; vol. 3: issue; 2: 290-300.
3. Kumar R, Patil S, Patil MB, Patil SR, Mshesh SP. Design and vitro evaluation of oral floating matrix tablets of aceclofenace. Chem Tech International journal of research;
(2009) Dec. Oct vol.1, No.4, pp. 815-825.
4. Yadav GV, Singh SR. Gastroretentive Drug delivery system of Lamotrigine: in VIVO Evaluation. International journal of pharmacy and pharmaceuticals science; (2014) vol.6, Issue 3, page no.279 -285.
5. Ahmad MG, Sanjana A. Vinay CH. Formulation and Evaluation of Gastro retentive Floating tablets of Rosuvastatin. European journal of pharmaceutical and Medical research (2016) march 13, 3(4)492-496.
6. Hartesi B, Abdassah M, Chaerunisaa Y.A, “starch as pharmaceutical excipient”
international journal of pharmaceutical sciences review and research. Dec (2016) article no 14 pages 59-64.
7. Deopa D, Kumar Singh K.S, Pathak S, Jindal K.N, “in vitro evaluation of controlled release containing aceclofenec microspheres” journal of pharmaceutical research and education. (2016) volume 1, Issue 1, pages 139-148.
8. Sager, Kishor, Savale. “Formulation and evaluation of microspheres with aceclofenac”
world journal of pharmaceutical and medical research. (2016) volume 2 Issue 4 page 181-187.
9. Kumar A, Renuka P, Babu A, Lakshmi L, “formulation and evaluation of floating pulsatile drug delivery system of acelofenac” indo American journal of pharmaceutical sciences.(2016) volume 3, Issue 4, pages 340-347.
10. Rao SK, Rakesh R, Udgirkar DB, Patil SP, Biradar VK, Gastro retentive Floating Matrix tablet of Cefpodoxime Proxetil General of Applied Pharmaceutical Science; (2011) Dec 28 01(10);190-194.
11. Soni T, Chotai N, Assessment of Dissolution Profile of Marketed Acelofenac Formulations J young Pharm 2010; 2 (1):21-26.
12. Pawar HA, Dhavale R, development and Evaluation of Gastroretentive Floating tablet of antidepressant Drug by thermoplastic Granulation Technique. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCE 3 (2014); 122-132.
13. Hwang KM, Cho CH ,Tung NT, Kim JY, Rhee YS, Park ES; Release Kinetic of Highly Porous floating tablet Containing Cilostazol. European general of Pharmaceutics and Biopharmaceutics (2017) Jan 29; 1-13.
14. Najafi RB, Mostafavi A, Tavakoli N, Taymouri S, Shahraki MM. Preparation and invitro-invivo evaluation of acyclovir Floating tablets. Research in pharmaceutical science, April (2017) ;12(2);128-136.
15. Upadhyay P, Nayak K, Patel K, Patel J, Saha H, Deshpande J, Formulation Development Optimization Evaluation of Sustained Release Tablet of Valacyclovir Hydrochloride By Combined Approach of floating and swelling For Better gastric Retention. Drug Deliv .and Trans. Res. (2014) 4; 452-464.
16. Goswami N, Joshi G, Sawant K, Floating microsphere of valacyclovir HCL:
Formulation, optimization, characterization, in vitro and in vivo Floatability Studies.
Journal of Pharmacy and Biallied Science (2012); 4:8-9.
17. Chauhan D, Shah S, “formulation and evaluation of pulsatile drug delivery system of aceclofenac for treatment of rheumatoid arthritis” international journal of pharmacy pharmaceutical sciences. 21 may (2012) volume 4, Issue 3, pages 1-7.
18. Sarkar D, Nandi G, Changder A, Hudati P, Sarkar S, Ghosh LK, Sustained release gastroretentive tablet of Metformin hydrochloride based on Poly (acrylic acid)-grafted- gellan. International journal of Biological macromolecules.2016. 12.022.
19. Mostafavi.A, Emami. J, Varshosaz. J, Davies. N.M. and Rezazadeh. (2011).
“Development Of A Prolonged-Release Gastroretentive Tablet Formulatin Of Ciprofloxacin Hydrochloride: Pharmacokinetic Characterization In Healthy Human Volunteers.” International Journal of Pharmaceutics.409 (2011) 128-136.
20. Isha C, Nimrata S, Rana A.C and Gupta S. (2012), “Oral Sustained Release Drug Delivery System: An Overview.” International Journal of Pharmacy. 3(5).
21. Gupta M.M. and Ray B. (2012).” A Review On: Sustained Release Technology.”
International Journal of Therapeutic Application. Volume 8 2012, 18-23.
22. Zalte H.D and Saudagar R.B. (2013). “Review on Sustained Release Matrix Tablet.”
International Journal of Pharmacy and Biological Science. 17-29.
23. Balata G. (2014). “Design and Evaluation of Gastroretentive floating tablet of Nizatidine:
A Trial to improve its Efficiency.” International Journal of Pharmacy and Pharmaceutical Science. Vol 6 issue 5.
24. Bhardwaj P, Chaurasia D, Singh, Swarup A. “development and characterization of noval site specific hollow floating microspheres bearing 5-fu for stomach targeting” the scientific world journal. (2014) volume 14 page 1-11.
25. Sharma D and Sharma A. (2014). “Gastroretentive drug delivery system: a mini review.”
Asian Pac. J. Health Sci.1 (2):80-89.
26. Kumar R, Chandra A and Garg S.(2012). “Formulation and in-vitro evaluation of sustained release gastroretentive tablets of Metformin Hydrochloride.” International Journal of Therapeutic Application. Volume 7.13-17.
27. Kumar K.P.S, Bhowmik D, Srivastava S, Paswan S and Datta A.S. “Sustained Release Drug Delivery System Potential.” The Pharma Innovation.
28. Kumar H, Kymonili K.M and Saraf S.A. (2012). “Gastroretentive ethyl cellulose floating microspheres containing Ranitidine Hydrochloride”. International Journal of Drug Development and Research. 0975-9344.
29. Shadab Md, Ahuja A, Khar R.K, Baboota S, Chuttani K, Mishra A.K. and Ali J. (2011).”
Gastroretentive drug delivery system of acyclovir loaded alginate mucoadhesive microspheres formulation and evaluation”. Informa healthcare.18 (4)255-264.
30. Hafeez A, Maurya A, Singh J, Mittal A. and Rana L. (2013).”An Overview of floating microsphere: Gastro retention floating drug delivery system (FDDS). The Journals of Phytopharmacology.2 (3)1-12.
31. Hafeez A, Maurya A, Singh J, Mittal A. and Rana L. (2013).”An Overview of floating microsphere: Gastro retention floating drug delivery system (FDDS). The Journals of Phytopharmacology.2 (3)1-12.
32. Jain ka , jain cp, tanwar ys, naruka ps (2009) “formulation characterization and in vitro evaluation of floating microspheres of famotidine as a gastro retentive dosage form” the Asian journal of pharmaceutics.7, page. 222-226.
33. Lj Josephine, Rt mehul, B Wilson, Bshanaz, Rbincy (2011) “formulation and in vitro evaluation of floating microspheres of anti-retro viral drug asa gastro retentive dosage form” the international journal of research in pharmacy and chemistry page. 519-527.
34. Dutta p, Sruti j, Patra ch, Rao bhanoji (2011) “floating microspheres recent trends in the development of gastroretentive floating drug delivery system” the international journal of pharmaceutical sciences and nanotechnology. Volume 4 issue 1 june 20011 page 1296- 1306.
.
