Formulation and Evaluation of Sustained Release Matrix Tablet of Anti-Amoebic Drug by Natural Polymers
Sunirmal Bhattacharjee*1, Nilayan Guha1, Gouranga Dutta1, Manas Chakraborty2, Mayukh Jana1, Susanta Paul1
*Corresponding author E-mail:
ABSTRACT:
The present study was to formulate Metronidazole sustained release matrix tablet using Xanthan gum, and guar gum as natural polymers and to elucidate the effect of type of polymers and its concentration on release pattern of drug from sustained release matrix tablets. Metronidazole matrix tablets were prepared in two batches (batch number F1 to F2) by direct compression method using xanthan gum and guar gum as natural polymers and Microcrystalline cellulose as a binder and pyrolidone as a water soluble polymer. The in vitro drug release studies of all the batches indicated that optimized formulation pertaining to Batch no. F2 was a promising system to provide sustained release effect of drug. The release pattern of the above formulation was best fitted to zero-order model and first order model. Mechanism of drug release followed was non-Fickian (super case-II) transport mechanism. Based on the above studies it can be concluded that this type of Anti-ameobic drug can be effectively formulated using different classes of natural polymers which can have greater bioavailability with less dose related side effects having better patient compliance.
KEYWORDS: Metronidazole, Guar gum, Xanthan gum, Microcrystalline cellulose, Pyrolidone, Talc..
INTRODUCTION:
Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals.[1][2][40,41,45,46] Drug delivery technologies modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. Drug release is from: diffusion, degradation, swelling, and affinity-based mechanisms.[3][29][30][32][36] Most common routes of administration include the preferred non-invasive peroral (through the mouth), topical (skin), transmucosal (nasal, buccal/sublingual, vaginal, ocularand rectal) and inhalation routes.[4][5][19][23][24][39]
Many drugs, peptide and protein, antibody, vaccine and gene based, in general may not be delivered using these routes because they might be susceptible to enzymatic degradation or cannot be absorbed into the systemic circulation efficiently due to molecular size and charge issues to be therapeutically effective. For this reason many protein and peptide drugs have to be delivered by injection or a nano-needle array.[18][22][26] [49][43]
To achieve and maintain the concentration of administered drug within the therapeutically effective range needed for a medication, it is often necessary to administer conventional dosage forms several times a day. These results in rise of drug level after each administration with subsequent fall which results in fluctuated drug level.[9][11][15][40][41][42]
The concept of sustained release was introduced in the early 1950s and the first patent on sustained release was obtained by Israel Lipowski who worked on coated pellets. There has been more than 50 years of research and development on sustained release dosage forms to prolong drug levels in the body. Successful fabrication of sustained release product is usually very difficult and involves consideration of physico-chemical parameters and pharmacokinetic behavior of drug, route of administration, disease state to be treated and, most important placement of the drug in the dosage form that will provide the desired temporal and spatial delivery pattern for the drug. Types of sustained release formulations include liposomes, drug loaded biodegradable microspheres and drug polymer conjugates[6][8][10][46][47]. Basically there are three basic modes of drug delivery, i.e. targeted delivery, controlled release and modulated release.
MATERIALS AND METHOD:
Materials Metronidazole was gift sample by Gluconate Health Limited., Kolkata.Guar gum, Xanthan gum was procured by Merck Specialities private Limited., India. Talc, Magnesium stearate was purchased from Apex Chemicals, Ahmedabad, India. Microcrystalline cellulose (MCC) Polyvinyl pyrolidone was purchased from Loba chemie Private Ltd. Mumbai.
METHOD:
Method for preparation sustained release matrix tablet of Metronidazole
The controlled release matrix tablets of metronidazole were prepared by the direct compression method. The drug, polymers and other excipients were passed through sieve # 80. The controlled release tablets containing drug, matrix materials, diluents, binder and lubricants were mixed uniformly and compressed on 10 station tablet machine using 8 mm round and flat punches with hardness between 5-7 kg cm-2.
The obtained micromeritic properties are given in Table no.2.The value of Angle of repose of formulation within the range of 30˚, indicating good flow properties for the granules. The tapped density values ranged between 0.510 ±0.08 to 0.608 ±0.04 g/ cm3 and the bulk density values ranged between 0.425 ±0.03 to 0.516 ±0.07 g/ cm3. The result of Carr’s Index range from 14.09 ±0.86 to 17.69 ±1.95 % suggests good flow characteristics of the granules. Hausner’s Ratio range from1.16 ±0.01 to1.21 ±0.09 % which indicates good flow property of microspheres.
RESULT AND DISCUSSION:
Preformulation Studies:
1. Standard Calibration Curve:
The λ max was found at 278 nm in 0.1 N HCl (PH- 1.2) and The standard calibration curve for Metronidazole with regression value of 0.983 are shown in figure 1 . The relation between drug concentration and absorbance is linear and the curve obeys Beer-lamberts law within the concentration range of 5 to 25 µg/ml of Metronidazole.
2. Differential Scanning Calorimetry Thermogram:
The supplied gift sample was identified by DSC thermogram. Identification of the drug can be described from the fig.8-10.
3. Drug Polymer Interaction Studies:
The FT-IR spectra analysis of losartan potassium and the physical mixtures shows that there was no significant interaction between drug and polymers as shown in Fig no.5-6.
Physico-chemical properties of matrix tablets of losartan potassium:
The thikness (mm), weight variation (%), Hardness (kg/cm2) Friability (%) and content uniformity (%) were calculated and the results are tabulated in table-3
Table 1: Formulation trials of 200 mg metronidazole SR tablets
|
Formulation Code |
Drug (mg) |
Xanthan gum (mg) |
Guar gum (mg) |
MCC |
PVP |
Talc |
Magnesium Stearate |
Total |
|
F1 |
200 |
100 |
- |
165 |
25 |
5 |
5 |
500 |
|
F2 |
200 |
|
100 |
165 |
25 |
5 |
5 |
500 |
Each formulation contains 10 tablets.
Table: 2 Micromeritic properties of formulation blends.
|
Formulation Code |
Angle of Repose |
Bulk Density |
Tapped Density |
Carr’s Index |
Hauner’s Ratio |
|
F1 |
24.03 ± 0.78 |
0.425 ±0.03 |
0.512 ±0.017 |
16.99 ±2.25 |
1.20 ±0.03 |
|
F2 |
26.61 ± 0.98 |
0.467 ±0.1 |
0.551 ±0.1 |
15.24 ±1.68 |
1.17 ±0.02 |
Table:3 Physico-chemical properties of matrix tablets of metronidazole.
|
Formulation Code |
Thickness (± S.D) (mm) |
Hardness (± S.D) (kg/cm2) |
Friability (± S.D) (%) |
Weight variation (± S.D) (%) |
Percentage Content (± S.D) (%) |
|
F1 |
0.574±0.054 |
6.73 ± 0.16 |
0.45 ±0.01 |
±2 |
99.79± 0.36 |
|
F2 |
0.596±0.070 |
6.79 ± 0.28 |
0.35 ±0.07 |
±1 |
99.96 ± 0.23 |
Fig:1 Standard curve of Metronidazole in 0.1N Hcl (PH 1.2)
Fig.2. FTIR spectra of Metronidazole
Fig. 3. FTIR spectra of Metronidazole and polymers ( Xanthan gum and Guar gum)
Fig. 4. DSC Thermogram of Metronidazole
Fog.5. DSC Thermogram of Metronidazole with Polymers
Fig:6.DSC Thermogram of Metronidazole and polymers comparison
In- Vitro Drug Release Studies:
It includes the dissolution of the matrix type tablet formulations study of all of the formulations by fitting the data obtained from dissolution study. In vitro release was carried out for all the formulations in 0.1 N HCl for 6 hours
Fig 7: Release Data to be Fitted in Zero order Release Kinetics for Formulations F1
Fig 8: Release Data to be Fitted in Zero order Release Kinetics for Formulations F2
Fig: 11. Release Data to be Fitted in Fitted in Higuchi Release Kinetics for Formulations F1
Fig: 12. Release Data to be Fitted in Fitted in Higuchi Release Kinetics for Formulations F2
Table 4:Statistical Evaluation of Release Data
|
|
Zero Order Model |
1st Order Model |
H-M Model |
|||
|
Formulations |
R2 |
Ko |
R2 |
K1 |
R2 |
Kh |
|
F1 |
0.955 |
4.35 |
0.890 |
0.208 |
0.947 |
11.88 |
|
F2 |
0.975 |
4.74 |
0.955 |
0.206 |
0.950 |
14.33 |
DISCUSSION:
From the dissolution profile study of two formulations of Metronidazole formulations namely: F1 and F2, it was found that the F2 formulations release profile best predicted by Zero order release kinetics named found to be the best released with R2 value of 0.994, which is nearer to 0.999. These properties and the viscous nature of the Guar gum retards release of the drug from the dosage form. This natural polymer is also appealing for use in drug delivery for a wide range of molecular weights, varying chemical compositions, low toxicity and biodegradability. The matrix tablets of xanthan gum, are given sustained release pattern of drugs from tablets. So it can be concluded from the above experiment that among al two formulations F2 shows best release profile in our laboratory atmosphere and set up.
ACKNOWLEDGEMENT:
The author Acknowledge the support of Bharat Technology, Uluberia, Howrah for providing infrastructural facilities to carry out this research work.
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Received on 30.03.2017 Modified on 27.04.2017
Accepted on 17.05.2017 © RJPT All right reserved
Research J. Pharm. and Tech. 2017; 10(7): 2041-2046.
DOI: 10.5958/0974-360X.2017.00356.0