DESIGN EXPERT SOFTWARE ASSISTED DEVELOPMENT AND EVALUATION OF CEFPODOXIME PROXETIL MATRIX TABLET
HTML Full TextDESIGN EXPERT SOFTWARE ASSISTED DEVELOPMENT AND EVALUATION OF CEFPODOXIME PROXETIL MATRIX TABLET
Shaikh Siraj N. * 1, Makrani Shaharukh Ismail 1, G. J. Khan 1, Siddiqi Hifjurrahman Md Athar 2 and R. L. Jadhav 3
Department of Pharmaceutics 1, Ali Allana College of Pharmacy Akkalkuwa, Nandurbar - 425415, Maharashtra, India.
Department of Pharmaceutics 2, Jamia College of Pharmacy, Akkalkuwa, Nandurbar - 425415, Maharashtra, India.
Department of Pharmaceutical Chemistry 3, Gourishankar Institute of Pharmaceutical Education and Research, Limb, Satara - 415001, Maharashtra, India.
ABSTRACT: Cefpodoxime Proxetil is third generation, broad-spectrum Cephalosporin Antibiotic & it has an oral bioavailability of only 50% and biological half life 2 h so to improve it’s bioavailability sustain release matrix formulation was designed. Sustained release matrix tablets of Cefpodoxime Proxetil prepared by direct compression method based on combination of natural Acacia gum & Karaya gum polymers. 32 full factorial designs optimization study was carried out by using Design Expert Software to find the effect of independent variables, i.e., Acacia gum (X1) and Karaya gum (X2) concentration on dependent variables i.e., Hardness & % CDR. The drug excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical studies, in-vitro drug release, kinetic studies and stability studies. FTIR and DSC studies shown there was no interaction between drug and polymers. Matrix tablet of Cefpodoxime Proxetil were formulated well in term of hardness 5.07 ± 0. 5.93 ± 0.03 kg/cm2, thickness 2.25 ± 0.1 mm to 3.33 ± 0.3 mm, weight variation were within limits. In-vitro release studies show that almost 90 % of drug was release from all the formulation were within 12 h. Formulation F5 selected as a optimized one since it showed optimum hardness & sustained drug release within 12 h in comparison to other formulation. The F5 optimized formulations were subjected to stability studies and shown there were no significant changes in drug content, physicochemical parameters and release pattern. 32 full factorial design optimization technique was successfully used in this research work. Developed matrix tablets of Cefpodoxime Proxetil produced a sustained and effective drug release over a prolonged time frame that led to greater therapeutic efficacy.
Keywords: |
Design Expert Software, Cefpodoxime Proxetil, Sustained release, Matrix tablets, Direct compression
INTRODUCTION: The oral route is the oldest and convenient route for the administration of therapeutic agents because of the low cost of therapy and ease of administration leads to a higher level of patient compliance 1.
Approximately 50% of the drug products available in the market are administered orally, and historically, oral drug administration has been the predominant route for drug delivery 2.
The goal of any drug delivery system is to provide a therapeutic amount of drug to the proper site in the body to achieve promptly and then maintain the desired drug concentration, i.e., the drug-delivery system should deliver the drug at a rate dictated by the needs of the body over a specified period of treatment 3, 4. Introduction of matrix tablet as sustained-release has given a new breakthrough for novel drug delivery systems in the field of Pharmaceutical technology 5, 6. Matrix systems are widely used for the purpose of sustained release. It is the release system that prolongs and controls the release of the drug that is dissolved or dispersed. By the sustained release method, therapeutically effective concentration can be achieved in the systemic circulation over an extended period of time, thus achieving better compliance of patients 7, 8.
Khandesh is a geographic area in Central India, which forms the northwestern portion of Maharashtra state. Khandesh District is a former governmental division of British India, which included the present-day Jalgaon, Dhule and Nandurbar districts, and a portion of Nasik District in Maharashtra.
Cefpodoxime Proxetil is a third-generation, broad-spectrum cephalosporin antibiotic mainly used in the treatment of respiratory, urinary, skin, and soft tissue infections caused by gram-positive and gram-negative bacteria. It is incompletely absorbed from the gastrointestinal tract and has an oral bioavailability of only 50% and biological half-life 2 h. Matrix tablet is able to prolong the release of drugs and thereby possibly improve oral bioavailability of Cefpodoxime Proxetil 9,10. Hence, in the present study, an attempt has been made to formulate the sustained release matrix tablets of Cefpodoxime Proxetil using natural polymers like karaya gum and acacia gum in various proportions as release controlling factor by direct compression which will improve its absorption.
MATERIALS AND METHODS:
Materials: Cefpodoxime Proxetil was procured as a gift sample from Shree Swami Samarth Ayurvedic Pharmacy Allopathic division, Jalgaon, Karaya gum procured from the local market Akkalkuwa in Khandesh region. Acacia gum, Magnesium stearate procured from SD Fine Chem. Ltd, Mumbai. Lactose & Talc from Research Lab Fine Chem Industries, Mumbai.
Method:
Formulation of Sustained Release Matrix Tablets: All the matrix tablets containing 100 mg of Cefpodoxime Proxetil, were prepared by direct compression method. Accurately weighed amounts of drug, polymer, and diluent were mixed geometrically in a mortar. This mixture was passed through no. 40 sieve and thoroughly mixed in a polythene bag for 15 min. The powder blend was then lubricated with magnesium stearate and talc for 2 min and compressed into tablets on a 9-station rotary tableting machine using 9-mm round, flat-faced punches. The total weight of the matrix tablets was 280 mg Table 3, with different drug-polymer ratios.
Drug - Excipient Compatibility Study: FTIR & DSC studies were conducted to know the compatibility between drug and excipients.
FT-IR Studies: FT-IR spectra for pure Cefpodoxime Proxetil and Different polymers acquired at room temperature using FT-IR spectrophotometer (FTIR-8400S, Shimadzu, Japan) in transmittance mode. The samples were ground in a mortar, mixed with Nujol and placed between two plates of KBr and compressed to form a thin film. The sandwiched plates were placed in the infrared spectrometer and the spectra were obtained. Scanning was performed between wave numbers 4000-400 cm-1. 11
DSC Analysis: Method for estimating the physical interaction between drug and polymers used for the formulation of different dosage forms is a thermal analysis by DSC. In the present studies, the DSC analysis of drug, and Polymers were carried out using a Shimadzu DSC 60, Japan; to evaluate any possible polymer drug thermal interaction. Exactly weighed 5 to 6 mg samples were hermetically sealed in aluminium crucible and heated at constant rate of 10 °C/min over a temperature range of 40 to 300 °C. Inert atmosphere was maintained by purging nitrogen gas at a flow rate of 50 ml/min.12
Evaluation of Sustained Release Matrix Tablets:
Pre-Compression Studies of Powder Blends: A preformulation study is the first step of insane drug development. All studies which are performed prior to the development of dosage form to reduce error and provide remunerative data to carry out dosage form development for the treatment of various diseases.
Angle of Repose: It is defined as the angle of heap to the horizontal plane. Angle of repose was determined by using fixed funnel method. Specified amount of powder drug was transferred to the funnel keeping the orifice of the funnel blocked by thumb. When the powder was cleared from funnel, then measured its angle of repose.
Angle of repose (θ) = tan-1 h/r
Bulk Density: It is the ratio of the bulk mass of powder to the bulk volume. It is calculated by this formula.
Bulk density = Weight of powder bulk / Bulk volume
Tapped Density: It is the ratio of the weight of blend to the minimum volume occupied in measuring cylinder by powder. The measuring cylinder containing the porous mass of powder was tapped using tapped density apparatus 13.
Tapped density = Weight of powder blend / Tapped volume of packing
Compressibility Indices:
Carr’s Index: Based on the apparent bulk density and the tapped density, the percentage compressibility of the powder mixture was determined by the following formula 14.
Carr’s index = Tapped density - Bulk density × 100/Tapped Density
Hausner’s Ratio:
Hausner’s ratio = Tapped density /Bulk density
Post-Compressional Studies of Prepared Matrix Tablets: The matrix tablets were evaluated for appearance, thickness, weight variation, hardness, and friability. All the evaluation parameters of all formulations are given in Table 2.
Thickness: The tablet thickness was calculated by Vernier calipers. Tablet was put in between two jaws vertically and measured thickness. It is expressed in mm.
Weight Variation: The weight of 20 tablets was measured, and the average weight was calculated. The individual weight of each tablet was measured to determine its variation. Weight variation was determined by comparison of individual tablet weight with average weight 15.
Hardness: The tablet hardness was determined by Monsanto hardness tester. The tablet was fitted lengthwise between plunger and force applied. Noted down the pressure at which the tablet was crushed. It is measured in kg/cm2. 6 tablets were used for this study 16.
Friability: It is calculated by the Roche friability apparatus. Preweighed six tablets were subjected to the device, which provided the combined effect of shock and abrasion from a height of six inches with each rotation, at 25 rpm speed, and operated for 100 revolutions. Tablets were dusted and re-weighed 9, 10. Compressed tablets that lose less than 0.5-1.0% of their weight were generally considered acceptable. It is expressed in percentage (%) and calculated by the following formula:
Friability (%) = Initial weight – Final weight/Initial weight × 100
Drug Content (Assay): Ten tablets were weighed and taken into a mortar and crushed into a fine powder. An accurately weighed portion of the powder equivalent to about 100 mg of Cefpodoxime Proxitil was transferred to a 100 mL volumetric flask containing 70 mL of 0.1N HCl. It was shaken by mechanical means for 1 h. Then it was filtered through a Whatman filter paper (no. 1) and diluted to 100 mL with 0.1N HCl. From this resulted solution, 1 mL was taken, diluted to 50 ml with 0.1N HCl, and absorbance was measured against blank at 258 nm.
In-vitro Drug Release Characteristics: Drug release was assessed by dissolution test under the following conditions: n = 3, USP type II dissolution apparatus (paddle method) at 100 rpm in 900 mL of 0.1N HCl for first 2 h and the phosphate buffer pH 6.8 from 3 to 12 h, maintained at 37 °C ± 0.5 °C. An aliquot (5mL) was withdrawn at specific time intervals and replaced with the same volume of prewarmed (37 °C ± 0.5 °C) fresh dissolution medium. The samples withdrawn were filtered through Whatman filter paper (no. 1), and drug content in each sample was analyzed by UV-visible spectrophotometer at 258 nm 17, 18.
Details of Dissolution Test:
Dissolution
test apparatus |
: | USPII |
Speed | : | 100 ± 0.1 rpm |
Stirrer | : | paddle type |
Volume of medium | : | 900 ml |
Time interval | : | 1, 2, 3, 4, 6, 8, 10 & 12 h |
Medium used | : | 0.1N HCl for first 2 h and the phosphate buffer pH 6.8 from 3 to 12 h |
Temperature | : | 37 ± 0.5 °C |
Kinetic Analysis of Dissolution Data: To analyze the in vitro release data, various kinetic models were used to describe the release kinetics.
Zero Order Rate Equation: Describes the systems where the drug release rate is independent of its concentration.
C =K0t……1
Where, K0 is zero-order rate constant expressed in units of concentration/time and t is the time.
First Order Equation: Describes the release from system where the release rate is concentration-dependent.
Log C = LogC0 - K1 t/2.303……2
Where, C0 is the initial concentration of drug, and K1 is first-order constant.
Higuchi Equation: Describe the release of drugs from the insoluble matrix as a square root of time dependent process based on Fickian diffusion Eq. (3).
Q = KHt1/2……3
Where, KH is the constant reflecting the design variables of the system.
Hixson-Crowell cube root law Equation: Describes the release from systems where there is a change in surface area and diameter of particles or tablets.
Q01/3 – Qt1/3 =KHC t……4
Where, Qt is the amount of drug remained in time t, Q0 is the initial amount of the drug in tablet, and KHC is the rate constant for the Hixson-Crowell rate equation.
Mechanism of Drug Release: Korsmeyer et al., (1983) derived a simple relationship which described drug release from a polymeric system Eq. (5). To find out the mechanism of drug release, first, 60% drug release data was fitted in
Korsmeyer–Peppas Model:
Mt / M∞=Ktn……5
Where Mt / M∞ is a fraction of drug released at time t, K is the release rate constant incorporating structural and geometric characteristics of the tablet, and n is the release exponent. The n value is used to characterize different release mechanisms19, 20.
Stability Studies of the Optimized Formulation: In the present study, stability studies were carried out at room temperature 40 ± 20 °C and 75 ± 5% RH for a specific time period up to 3 Months for selected F5 formulations. For stability study, the tablets were sealed in aluminum packaging coated inside with polyethylene & studied for various parameters 21.
Optimization by using Full Factorial Design: 22 In the present study, a 32 full factorial design was employed to study the effect of independent variables, i.e., amount of Acacia gum (X1) and Karaya gum (X2) on dependent variables, i.e., Hardness,% CDR.
TABLE 1: LAYOUT OF 32 FULL FACTORIAL DESIGN BATCHES OF MATRIX TABLETS F1-F9
Batch no. | X1 | X2 |
F1 | -1 | -1 |
F2 | -1 | 0 |
F3 | -1 | 1 |
F4 | 0 | -1 |
F5 | 0 | 0 |
F6 | 0 | 1 |
F7 | 1 | -1 |
F8 | 1 | 0 |
F9 | 1 | 1 |
TABLE 2: TRANSITION OF CODED VALUE IN AN ACTUAL UNIT
Coded value | Acacia gum (X1) | Karaya gum (X2) |
-1 | 30 | 30 |
0 | 40 | 60 |
1 | 50 | 90 |
TABLE 3: COMPOSITION OF MATRIX TABLETS CONTAINING KARAYA GUM AND ACACIA GUM
Ingredients | F1 (mg) | F2 (mg) | F3 (mg) | F4 (mg) | F5 (mg) | F6 (mg) | F7 (mg) | F8 (mg) | F9 (mg) |
Cefpodoxim Proxetil | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
Karaya gum | 30 | 30 | 30 | 60 | 60 | 60 | 90 | 90 | 90 |
Acacia gum | 30 | 40 | 50 | 30 | 40 | 50 | 30 | 40 | 50 |
Magnesium Stearate | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Talc | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Lactose | 100 | 90 | 80 | 70 | 60 | 50 | 40 | 30 | 20 |
Total weight | 280 | 280 | 280 | 280 | 280 | 280 | 280 | 280 | 280 |
RESULTS:
FTIR:
FIG. 1: FTIR SPECTRUM OF CEFPODOXIME PROXETIL (PURE DRUG)
FIG. 2: FTIR SPECTRUM OF KARAYA GUM
FIG. 3: FTIR SPECTRUM OF CEFPODOXIME PROXETIL WITH KARAYA GUM
FIG. 4: FTIR SPECTRUM OF ACACIA GUM
FIG. 5: FTIR SPECTRUM OF CEFPODOXIME PROXETIL WITH ACACIA GUM
FIG. 6: FTIR SPECTRUM OF BLEND (CEFPODOXIME PROXETIL + KARAYAGUM + ACACIA GUM)
All the characteristic peaks of Cefpodoxime Proxetil were present in spectra, thus indicating compatibility between drug. It shows that there was no significant change in the chemical integrity of the drug.
DSC:
FIG. 7: DSC ANALYSIS OF CEFPODOXIME PROXETIL (PURE DRUG)
FIG. 8: DSC ANALYSIS OF BLEND (CEFPODOXIME PROXETIL + KARAYA GUM + ACACIA GUM)
DSC study shows an endothermic peak at 96.77 °C correspond to the melting point of Cefpodoxime Proxetil in formulation blend no significant changes in characteristic endothermic peak of Cefpodoxime Proxetil that indicate there is compatibility of drug within formulation blend.
Pre-compression Parameters: The prepared formulations were evaluated for precompression parameters, and their results were given in Table 4. The powder blend was evaluated for various parameters like angle of repose, tapped density, bulk density, Carr’s index, and Hausner’s ratio, respectively. The value of the angle of repose of all formulations ranges between 25.64 ± 0.11 to 28.75 ± 0.22 (θ), which shows very good powder flow property. The result of bulk density and tapped density ranges from 0.21 ± 0.1 to 0.51 ± 0.04 g/ml and 0.25 ± 0.03 to 0.59 ± 0.06 g/ml respectively. The values of compressibility indices and Hausner’s ratio ranged from 7.18 ± 0.04 to 15.90 ± 0.09 and 1.07 ± 0.09 to 1.18 ± 0.09, respectively.
Post-compression Parameters: The weight of Cefpodoxime proxetile matrix tablets was found to be in the range of 289 ± 0.2 ± 0.004 to 297 ± 0.3 ± 0.002 gm. Thickness was observed as 2.25 ± 0.1mm to 3.33 ± 0.3 mm and % friability of various formulations was found to be in between 0.25 ± 0.009 to 0.64 ± 0.011. The hardness of the tablet was found to be 5.07 ± 0. 5.93 ± 0.03 kg/cm2. The in-vitro drug release that was performed for karaya and acacia gum containing formulations.
The % in-vitro drug release from formulations F1, F2, F3, F4, F5, F6, F7, F8 and F9 at the end of 12 h was found to be 97.20 ± 0.032%, 96.30 ± 0.01%, 95.40 ± 0.056%, 94.50 ± 0.013%, 98.10 ± 0.067%, 93.60 ± 0.045%, 92.70, 91.80, & 90.09% respectively. Drug release kinetics parameters with n, R2 value are provided in Table 8. The regression coefficient value of zero order was observed R2 value 0.9814 so, the drug release was found to be zero order kinetics.
TABLE 4: PRE-COMPRESSION PARAMETER OF BLEND
Parameter
Batches |
Bulk Density
(gm/cm3) (mean ± SD) |
Tapped Density
(gm/cm3) (mean ± SD) |
Compressibility
Index (%) |
Hausner’s Ratio | Angle of
Repose (o) |
F1 | 0.29 ± 0.04 | 0.31 ± 0.02 | 7.91 | 1.08 | 25.64 |
F2 | 0.29 ± 0.09 | 0.31 ± 0.01 | 7.52 | 1.08 | 26.56 |
F3 | 0.29 ± 0.02 | 0.32 ± 0.04 | 7.18 | 1.07 | 27.47 |
F4 | 0.21 ± 0.1 | 0.25 ± 0.03 | 14.74 | 1.17 | 27.02 |
F5 | 0.48 ± 0.03 | 0.53 ± 0.03 | 9.12 | 1.10 | 26.38 |
F6 | 0.52 ± 0.01 | 0.59 ± 0.06 | 12.53 | 1.14 | 28.75 |
F7 | 0.48 ± 0.06 | 0.57 ± 0.08 | 15.90 | 1.18 | 27.33 |
F8 | 0.41 ± 0.04 | 0.48 ± 0.01 | 14.69 | 1.17 | 26.43 |
F9 | 0.51 ± 0.04 | 0.59 ± 0.01 | 13.70 | 1.15 | 27.34 |
TABLE 5: POST-COMPRESSION PARAMETER OF FORMULATION F1-F9
Formulation | Thickness (n=3)
(mm) (SD) |
Hardness
(kg/cm2) (n=3) (SD) |
Friability
(%) (n=10) |
Weight Variation
(n=20) (mg) (SD) |
Drug content
(%) |
F1 | 2.25 ± 0.1 | 5.93 ± 0.03 | 0.33 | 293 ± 0.4 | 98.50 ± 0.2 |
F2 | 2.35 ± 0.3 | 5.07 ± 0.04 | 0.30 | 297 ± 0.3 | 96.50 ± 0.4 |
F3 | 3.20 ± 0.3 | 5.08 ± 0.06 | 0.20 | 295 ± 0.7 | 93.51 ± 0.6 |
F4 | 3.14 ± 0.2 | 5.50 ± 0.10 | 0.33 | 291 ± 0.1 | 92.55 ± 0.2 |
F5 | 3.33 ± 0.3 | 5.66 ± 0.06 | 0.25 | 289 ± 0.2 | 99.48 ± 0.8 |
F6 | 3. 11 ± 0.4 | 5.41 ± 0.07 | 0.15 | 294 ± 0.5 | 95.39 ± 0.7 |
F7 | 3.20 ± 0.3 | 5.16 ± 0.02 | 0.64 | 296 ± 0.2 | 94.03 ± 0.2 |
F8 | 2.98 ± 0.3 | 5.08 ± 0.02 | 0.48 | 297 ± 0.1 | 91.99 ± 0.2 |
F9 | 3.15 ± 0.2 | 5.25 ± 0.05 | 0.42 | 294 ± 0.4 | 90.51 ± 0.4 |
The hardness of the tablet is defined as the force applied across the diameter of the tablet in order to break the tablet. The hardness of the formulations F1-F9 was observed within the range of 2.25 ± 0.1 to 3.11 ± 0.4 kg/cm2 as shown in Table 5.
All the polynomial equations for hardness variable were found to be statistically significant as determined using ANOVA, as per the provision of Design-Expert software.
FIG. 9: RESPONSE SURFACE PLOTS PRESENTING THE EFFECTS OF ACACIA GUM (X1) AND KARAYA GUM AMOUNT (X2) ON HARDNESS
FIG. 10: CONTOUR PLOTS PRESENTING THE EFFECTS OF ACACIA GUM (X1) AND KARAYA GUM AMOUNT (X2) ON HARDNESS
TABLE 6: IN-VITRO DRUG RELEASE STUDY OF FORMULATION F1-F9
Time (hrs) | Cumulative % Drug Release | ||||||||
F1 | F2 | F3 | F4 | F5 | F6 | F7 | F8 | F9 | |
0 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
1 | 1.35 | 11.70 | 15.30 | 8.10 | 9.90 | 10.80 | 7.20 | 8.10 | 13.50 |
2 | 13.50 | 19.35 | 20.70 | 18.90 | 22.50 | 17.10 | 17.10 | 18.90 | 17.10 |
3 | 19.80 | 27.00 | 24.30 | 25.20 | 26.10 | 23.40 | 22.50 | 24.30 | 24.30 |
4 | 38.70 | 37.80 | 34.20 | 36.90 | 34.20 | 33.30 | 31.50 | 32.40 | 31.50 |
5 | 44.10 | 43.20 | 40.50 | 43.20 | 40.50 | 36.90 | 39.60 | 37.80 | 40.50 |
6 | 45.90 | 45.00 | 48.60 | 45.00 | 44.10 | 46.80 | 44.10 | 43.20 | 45.90 |
7 | 61.20 | 51.30 | 53.10 | 49.50 | 50.40 | 52.20 | 47.70 | 48.60 | 50.40 |
8 | 68.40 | 62.10 | 55.80 | 62.10 | 61.20 | 54.00 | 61.20 | 59.40 | 62.10 |
9 | 76.50 | 65.70 | 71.10 | 71.10 | 70.20 | 67.50 | 66.60 | 67.50 | 66.60 |
10 | 84.60 | 77.40 | 75.60 | 79.20 | 76.50 | 72.90 | 77.40 | 74.70 | 80.10 |
11 | 89.82 | 89.10 | 87.30 | 84.60 | 88.20 | 83.70 | 82.80 | 85.50 | 85.50 |
12 | 97.20 | 96.30 | 95.40 | 97.23 | 98.10 | 96.60 | 92.70 | 93.80 | 90.09 |
FIG. 11: RESPONSE SURFACE PLOTS PRESENTING THE EFFECTS OF ACACIA GUM (X1) AND KARAYA GUM AMOUNT (X2) ON %CDR
FIG. 12: CONTOUR PLOTS PRESENTING THE EFFECTS OF ACACIA GUM (X1) AND KARAYA GUM AMOUNT (X2) ON %CDR
FIG. 13: % DRUG RELEASE OF CEFPODOXIME PROXETIL IN FORMULATION F1-F9
TABLE 7: RESULT OF ANOVA
Response model | Sum of square | Degree of freedom | Mean square | F value | P value | R square | Ade. Precision |
Hardness | 0.99 | 5 | 0.182 | 4.88 | Significant | 0.9770 | 6.36 |
%CDR | 91.20 | 5 | 17.64 | 10.74 | Significant | 0.8023 | 9.63 |
TABLE 8: IN-VITRO DRUG RELEASE STUDY OF FORMULATION F5
Batch | Zero order | First order | Higuchi | Hixson- Crowell | Korsmeyer-Peppas | ||||||
F5 | r2 | K0(h-1) | r2 | K1(h-1) | r2 | KH (h-1/2) | r2 | KHC (h-1/3) | r2 | n | KKP(h-n) |
0.9814 | 7.6770 | 0.8277 | -0.1803 | 0.8853 | 21.5000 | 0.9013 | -0.0422 | 0.9544 | 1.4900 | 2.8307 |
* r2= Correlation coefficient; K = Kinetic constant; n= Diffusional exponent
TABLE 9: STABILITY STUDY OF OPTIMIZED BATCH (F5)
Parameters | Time
(months) |
Hardness
(kg/cm2) |
Friability
(%) |
Drug content
(%) |
% drug
Release |
Before
stability study |
0 | 5.66 ± 0.06 | 0.26 | 99.48± 0.8 | 98.15 |
After
stability study |
3 | 5.14 ± 0.03 | 0.25 | 98.87± 0.68 | 97.10 |
FIG. 14: KINETIC ANALYSIS OF DISSOLUTION DATA OPTIMIZED BATCH (F5)
DISCUSSION:
Pre-compression Study of Powder Blend: The powder blend was evaluated for various parameters as shown in Table 4. This showed that powder blend from all the formulations showing good flow property according to standard values 23.
Post-compression Studies of Prepared Matrix Tablets: The results of post-compression evaluation parameters are given in Table 5, and its description is given below.
Thickness: The determined thickness, according to the die and punches size of all formulation, was found to be 2.25 ± 0.1 mm to 3.33 ± 0.3 mm. It was upon the die and punched size during compression of tablets and their total weight.
Weight Variation: The determined weight variation of formulating tablets was found to be in the range of 289 ± 0.2 ± 0.004 to 297 ± 0.3 ± 0.002 gm. It was found to be within pharmacopeias limit of ± 5% as per I.P 24.
Hardness: The hardness of tablet (n=3) of formulation code F1, F2, F3, F4, F5, F9, which was given satisfactory result as per standard. On increasing the concentration of polymer hardness was also increases gradually. Since a high concentration of natural polymer enhances more hardness than natural polymer.
% Friability: The result of friability was found to be 0.25 ± 0.009 to 0.64 ± 0.011, which was less than 1% as per the pharmacopeias limit. The highest concentrations of polymers in the matrix tablet also affect the friability. It showed that tablets have sufficient strength to tolerate transportation stress 25.
In-vitro Drug Release Study: The in-vitro drug release was carried out in 0.1 n HCl for 2 h and phosphate buffer of pH 6.8. The formulations F1 to F9 were given sustained drug release profile for 12 h study as 97.20 ± 0.032%, 96.30 ± 0.01%, 95.40 ± 0.056%, 94.50 ± 0.013%, 98.10 ± 0.067%, 93.60 ± 0.045%, 92.70, 91.80, & 90.09% respectively. The optimized formulation profile was given by F5.
In-vitro Drug Release Kinetics: The release kinetics model was used for the goodness of fit by linear regression analysis with the help of zero order, first order, Higuchi’s, and Korsmeyer Peppas equation in order to determine release and mechanism of drug action. The regression coefficient value of zero-order was observed R2 value 0.9814. So, the drug release was found to be zero-order kinetics. The first order equation depends upon the Noyes Whitney equation. Higuchi describes the release of drugs from the insoluble matrix as the square root t dependent release, and R2 value was found to be 0.8853. Korsmeyer Peppas describe the mechanism of drug release was found to be non-fickian super case II 26.
Stability Studies: In the present study, stability studies were carried out at room temperature 40 ± 20 °C and 75 ± 5% RH for a specific time period up to 3 months for selected F5 formulations. For stability study, the tablets were sealed in aluminum packaging coated inside with polyethylene & studied for various parameters. The outcome of stability studies is no significant change in all parameters after stability study, so the formulation is stable 27.
CONCLUSION: The Matrix tablet of Cefpodoxime Proxetil was prepared by a direct compression method using different natural polymers such as karaya gum and acacia gum in different concentrations. From FTIR, DSC, and physical observation it can be concluded that there is no significant drug excipient interaction, so drug and other excipient are compatible with each other. Matrix tablet of Cefpodoxime Proxetil were formulated well in term of hardness 5.07 ± 0. 5.93 ± 0.03 kg/cm2, thickness 2.25 ± 0.1 mm to 3.33 ± 0.3 mm, weight variation 289 ± 0.2 ± 0.004 to were within 12 h. Formulation F5 showed sustained drug release within 12 h in comparison to other formulation.
Stability studies were conducted for the F5 formulation at 40 °C/75% RH for 3 months. Various parameters like hardness, thickness, drug content, and dissolution rate were analyzed at a time interval of 1 month till the period of 3 months.
Not much variation or change was observed in any parameters throughout the study period. Best formulation batch F5 drug content is 98% found to be stable.
ACKNOWLEDGEMENT: The authors are thankful to Hazrat G. M. Vastanvi, President of Ali Allana College of Pharmacy Akkalkuwa for providing the research facilities, Shree Swami Samarth Ayurvedic Pharmacy, Jalgaon for gift samples of Cefpodoxime Proxetil, Maliba College of Pharmacy Bardoli District Surat for FTIR Study, & R. C. Patel College of Pharmacy Shirpur for FTIR & DSC Study.
CONFLICTS OF INTEREST: Nil
REFERENCES:
- Lachman L, Lieberman HA and Kanig JL: The theory and practice of industrial pharmacy. 3rd Varghese publishing house 1991: 67-71.
- Chiao CSL and Robinson JR: Sustained - release drug delivery Systems. Remington’s Pharmaceutical Sciences, 19th, Mac Publishing Company 1999: 1660-3.
- Indian Pharmacopoeia: Ministry of Health and Family Welfare, Government of India. Published by The Indian Pharmacopoeial commission: Ghaziabad 2010; I(II): 193, 751-3, 1199.
- Modi SA, Gaikwad PD, Bankar VH and Pawar SP: Sustained release drug delivery system: A review, IJPRD 2011; 2(12): 147-60.
- Wise DL: Handbook of Pharmaceutical Controlled Release Technology, New York: Marcel Dekker, Inc; First ed. Indian reprint 2005: 211, 431.
- Chein YW: Oral drug delivery and delivery systems, 2nd Marcel Dekker – Inc, New York 1992: 139-1.
- Chein YW: Rate controlled drug delivery systems. Ind J Pharm Sci 1988: 63-5.
- Pachuau L, Sarkar S and Muzumder B: Formulation and evaluation of matrix microspheres for simultaneous delivery of Salbutamol Sulphate and Theophyllin. Trop J Pharm Res 2008; 7(2): 995-1002.
- Swain RP, Kumari TP and Panda S: Formulation development and evaluation sustained release Ibuprofen tablets with acrylic polymers and HPMC. Int J Pharm Pharm Sci 2015; 8(2): 131-35.
- Mehta P, Deshmukh GJ, Seth AK and Patel B: Formulation and evaluation of sustained release matrix tablet of Captopril. IAJPR 2011; 2(1): 69-83.
- Barot N, Modi D and Bhardia PD: Formulation development and evaluation of sustained release matrix tablets of Repaglinide. IJPRBS 2014; 3(2): 370-96.
- Zheng ZC, Wang XY and Du XJ: Preparation and characterization of sustained release matrix tablets of Tizanidine Hydrochloride for spinal injuries. Trop J Pharm Res 2015; 14(10): 1749-54.
- Mohammad P and Khaled T: Development and evaluation of sustained release matrix tablets of Ketoprofen employing natural polymers. JOCPR 2016; 8(4): 822-27.
- Costa P and Lobo JMS: Modeling and comparison of dissolution profiles. EJPS 2001; 13: 123-33.
- Rahman Z, Ali M and Khar R: Design and evaluation of bilayer floating tablets of captopril. Acta Pharm 2006; 56: 49-57.
- Vidyadhara S, Choudhary YA, Murthy TE, Rao MV and Reddy KN: Influence of electrolyte on controlled release of Ambroxol hydrochloride from methocel matrix tablet. Pharma Review 2006; 101-04.
- Remington: The Science and practice of pharmacy, 20th edition. Lippincott Williams & Wilkins 2002; 903-14.
- Vidyadhara S, Rao PR and Prasad JA: Development and in-vitro kinetics of propanolol hydrochloride controlled release matrix tablets. Indian Pharm 2006; 5: 66-70.
- Robinson JR and Lee VH: Controlled drug delivery, 2nd Marcel Dekker 1987: 4-15.
- Varshosaz J, Tavakoli N and Roozbahani F: Formulation and in-vitro characterization of Captopril floating extended release tablet. Drug Deliv 2006; 13: 277-85.
- Sultana S and Mohammed S: A review on stability studies of pharmaceutical products. IJPRS 2018; 7(1): 28-49.
- Fulbandhe VM and Jobanputra CR: Evaluation of release retarding property of gum damar and gum copal in combination with HPMC. IJPS 2012; 74(3): 189-94.
- Gilbert’s B and Christopher R: Modern pharmaceutics. 4th Marell Dekker 1996: 503-13.
- Thakkar V, Shaikh V, Soni T and Gandhi T: Design and evaluation of sustained release enteric coated dosage form of fluoxetine hydrochloride. Indian Journal of Pharmaceutical Education and Res 2012; 46(4): 330-9.
- Kumar MV, Harani VA, Padmasri S, Kartika D and Chandra M: Formulation and evaluation of sustained release hydrophilic matrix tablet of diclofenac sodium using natural gum. Inventi Rapid 2012; 1087-94.
- Emami J, Tajeddin M and Ahmadi F: Preparation and in-vitro evaluation of sustained-release matrix tablets of flutamide using synthetic and naturally occurring polymers. Int J of Pharma Res 2008; 7(4): 247-57.
- Aulton ME: Pharmaceutics - The science of dosage form design, 2nd edition; 2013; 360-461.
How to cite this article:
Siraj NS, Ismail MS, Khan GJ, Athar SHM and Jadhav RL: Design expert software assisted development and evaluation of cefpodoxime proxetil matrix tablet. Int J Pharm Sci & Res 2020; 11(5): 2431-43. doi: 10.13040/IJPSR.0975-8232.11(5).2431-43.
All © 2013 are reserved by the International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Article Information
55
2431-2443
890
1092
English
IJPSR
N. S. Siraj *, M. S. Ismail, G. J. Khan, S. H. M. Athar and R. L. Jadhav
Department of Pharmaceutics, Ali Allana College of Pharmacy Akkalkuwa, Nandurbar, Maharashtra, India.
Sirajsk1234@gmail.com
19 December 2019
27 February 2020
30 March 2020
10.13040/IJPSR.0975-8232.11(5).2431-43
01 May 2020