Formulation And In-Vitro Evaluation of Compression Coated Core Tablets of Metronidazole for Colon Specific Drug Delivery

Ayesha Sultana , H. Doddayya, Soukhya Joshi G., Saqib Akram Wani, Sushma, Touseef, Vanishree K., Pradnya B. Patil, Sarfaraz MD,

doi:10.5281/zenodo.15421663

Research Paper | Open Access
Volume 03 | Issue 05 | Article Id IJPS/250304708

Formulation And In-Vitro Evaluation of Compression Coated Core Tablets of Metronidazole for Colon Specific Drug Delivery
Ayesha Sultana * H. Doddayya Soukhya Joshi G. Saqib Akram Wani Sushma Touseef Vanishree K. Pradnya B. Patil Sarfaraz MD
N.E.T Pharmacy College Raichur.

Abstract

The study aimed to formulate and evaluate colon-specific compression-coated core tablets of Metronidazole for treating intestinal amoebiasis, focusing on improved efficacy, reduced dosing frequency, and enhanced patient compliance. Core tablets were prepared using wet granulation method with PVP K-30 as a binder and sodium starch glycolate as a disintegrant. Compression-coated tablets utilized varying ratios of chitosan and Carbopol 934P polymers. Granules were assessed for physical properties like angle of repose, bulk density, compressibility index, etc. Tablets underwent tests for weight variation, hardness, friability, drug content, and in-vitro drug release. Results showed polymer ratios significantly influenced Metronidazole release, with F1 and F2 formulations meeting prescribed limits and exhibiting good appearance.

Keywords

Metronidazole, PVP K-30, Chitosan, Carbopol 934P, Colon targeted tablets, Sodium starch glycolate.

Introduction

Colon-specific drug delivery systems (CDDS) focus on delivering drugs directly to the colon, improving treatment of local diseases like intestinal amoebiasis, ulcerative colitis, and irritable bowel syndrome, while minimizing systemic side effects. By bypassing the upper gastrointestinal (GI) tract, drugs such as sulfasalazine, dexamethasone, and metronidazole achieve higher concentrations in the colon1. The colon's neutral pH, long transit time, reduced enzymatic activity, and high enzyme presence make it an ideal drug delivery site. CDDS methods2 include pH-sensitive polymers, time-dependent systems, and enzymatically controlled delivery systems3. Compression coating, also known as solvent-less or dry coating, offers advantages over solvent-based techniques, including shorter processes and the ability to achieve delayed or colon-specific release. It involves compressing coating materials around a preformed core tablet without solvents, creating two parts: the internal core and the surrounding coat. This method ensures precise placement and controlled drug release while maintaining simplicity in manufacturing.

MATERIALS AND METHODS

Metronidazole was obtained as a gift sample (Divine Laboratories, Hyderabad) and other chemicals and polymers like Carbopol 934P (BENEO-Palatinit, Germany) and all the chemicals were obtained from different reputed companies.

METHOD:

Preparation of Metronidazole core tablet by wet granulation method:

1. The core tablets were prepared by wet granulation technique by using PVP-K30 solution as binder. Lactose was used as diluent and sodium starch glycolate as disintegrant.
2. All the ingredients were thoroughly mixed and then a damp mass is prepared by using PVP-K30 solution as a binder.
3. The damp mass was passed through sieve no.10, the granules were dried in the hot air oven, and then dried granules were passed through sieve no.20.
4. The granules were lubricated with mixture of talc and magnesium stearate.
5. The granules were compressed into the tablets using Tablet Compression Machine.

Preparation of metronidazole compression coated core tablet:

a) The coated core tablet of Metronidazole was compressed with different polymers i.e. Carbopol 934P and Chitosan.

b) 40 percent of coat weight was placed in the die cavity below of the tablet compression machine followed by placing core tablet in the centre and addition of remaining coating material on it.

c) The coating material was compressed around the core tablet with high compression force.

Table 1: Formula of compression coated core tablets of Metronidazole

Ingredients (mg)	Formulations
Ingredients (mg)	F-1	F-2
Metronidazole	200	200
Lactose	72.5	22.5
Sodium starch glycolate	10	10
PVP K-30 (binder)	10	10
Talc	5	5
Magnesium stearate	2.5	2.5
Carbopol 934P	100	150
Chitosan	100	100
Total	500mg	500mg

Evaluation of tablets:

Thickness and diameter⁴: The thickness and diameter of the tablet was measured using vernier calliper (Mitutoyo, Japan) and screw gauge. The measurements were in mm. Average of three readings were taken and the results were tabulated.

Hardness test⁵: Prepared tablets were subjected for hardness by using Pfizer hardness tester. Hardness was expressed in kg/cm². Triplicate readings were taken and average was computed.

Weight uniformity⁶: Randomly selected 10 tablets were subjected to weight uniformity test.

Friability test (F)⁷: Tablet friability was tested using Roche Friabilator. The percentage friability was calculated by using the following formula.

Percentage friability = ???????????????????????????? ???????????????????????? – ???????????????????? ???????????????????????? ×100/ Initial weight

Drug content uniformity⁸: For compression-coated core tablets of Metronidazole, randomly selected tablets were weighed, powdered, and a quantity equivalent to 25 mg of the drug was dissolved in ethanol. After shaking for 60 minutes with an initial 30 ml of ethanol, the solution volume was adjusted to 50 ml, left undisturbed for 1 hour, and filtered. Desired dilutions were prepared using phosphate buffer (pH 6.8) and analysed for drug content at 318 nm, with phosphate buffer (pH 6.8) as a blank. Triplicate readings were taken, and the average was calculated.

In-vitro dissolution study⁹: In-vitro dissolution studies assessed the ability of Metronidazole compression-coated tablets to remain intact in the stomach and small intestine. Two formulations were tested using USP XXIII test apparatus at 75 rpm and 37±1ºC. Tablets were placed in a basket with 900 ml of 0.1M HCL for 2 hours, followed by pH 7.4 phosphate buffer for 3 hours, and then pH 6.8 phosphate buffer for up to 12 hours. Samples (1 ml) were collected hourly, replenished with fresh buffer, filtered, and analyzed at 318 nm using a UV-visible spectrophotometer. Drug content was determined using a standard calibration curve. Kinetic study14,15: In order to analyse the release mechanism, several release models were tested such as Zero Order, First order, Higuchi, Korsmeyer -Peppas.

Fourier Transform Infrared Spectroscopy studies (FTIR)10,11: The Pure drug and selected formulations (F1) were subjected for FTIR analysis to check the compatibility/interaction between the drug and excipients.

RESULTS

Fig 1: FTIR spectra of pure drug Metronidazole

Fig 2: FTIR spectra of chitosan polymer

Fig 3: FTIR spectra Carbopol 934P polymer

Fig 4: FTIR spectra of Metronidazole compression coated core tablet

Table 2: Post Com. Pressional Parameters Core Coat Tablets of Metronidazole

Batches

Weight variation in mg±SD

Diameter in mm±SD

Thickness in mm±SD

Friability in

%±SD

Hardness in kg/cm²±SD

Drug content in

%±SD

501±1.528

10±0.500

5.3±0.25

0.82±0.02

3±0.571

98%

495±1.234

10±0.500

4.4±0.20

0.44±0.01

2.5±0.20

93%

*Average of three determinations

Fig 5: In-vitro dissolution profile of F1 with model fit curve

Fig 6: In-vitro dissolution profile of F2 with model fit curve.

Table 3: In-vitro dissolution data of F1 and F2 compression coated core tablets.

Time in Hours	*Cumulative per cent drug release±SD**
Time in Hours	F1	F2
0.5	0.000±0.00	0.5
1	0.180±0.03	1
2	0.378±0.03	2
3	0.497±0.03	3
4	0.618±0.03	4
5	0.857±0.03	5
6	6.024±0.03	6
7	9.002±0.03	7
8	23.775±0.03	8
9	49.917±33.97	9
10	53.352±0.03	10
11	91.042±0.12	11
12	98.002±0.15	12

Averages of three determinations

Table 4: In-vitro model fitting values for compression coated core tablets for F1 and F2

Batches	Zero order	First order	Matrix	Peppas		Hixon
Batches	R	R	R	R	n	R
F1	0.7805	0.6625	0.6162	0.9185	2.8635	0.7158
F2	0.8423	0.7127	0.6737	0.9304	2.9091	0.7772

DISCUSSION

Colon-targeted drug delivery improves local treatment of conditions like intestinal amoebiasis, Crohn’s disease, ulcerative colitis, and IBS, while reducing systemic side effects. Metronidazole, an antibiotic for GI disorders, was formulated into compression-coated core tablets to achieve targeted colon release and reduce dosing frequency. Compression coated core tablet is a system in which the entire surface of an inner core is completely surrounded by the coat. These coats prevent drug release from the core until the polymeric or drug coat is entirely eroded, dissolved or removed. The technique, a simple and unique technology, is used to provide tablets with a programmable lag phase, followed by a fast or rate-controlled drug release. The present study was an attempt to formulate compression coated core tablets of Metronidazole using various novel polymers such as chitosan and Carbopol 934P in different ratios by wet granulation method.

Post-compression studies

Thickness of the Metronidazole compression coated core tablet was found to be in the range of 5.3±0.252 mm to 4.4±0.200 mm for F-1 to F-2 formulations. The hardness of the tablet was found to be in the range of about 3±0.577 kg/cm2 to 2.5±0.200 kg/cm2 and friability was found to be in the range of 0.82±0.025 to 0.45±0.015 % which was below 1% indicating the sufficient mechanical integrity and strength of the prepared tablets. The hardness and friability data indicates good mechanical strength/resistance to the tablets. The weight variation results revealed that average percentage deviation for 10 tablets was less than±10%, which provide good uniformity of the tablets , whereas the percentage drug content was found to be in the range of 95.14 % to 97.4 %. The low SD values indicate the drug content was uniform in all the formulated tablets in In-vitro drug release study. The results were given in Table 2. FTIR studies is a measurement of possible interaction between and excipients is an important part in the fabrication of formulation. Hence, FTIR studies were conducted to assess interaction between drug and polymers. In-vitro dissolution study: The compression coated core tablets of Metronidazole to remain intact in the physiological environment of stomach and small intestine assessed by conducting in-vitro dissolution studies. F1 and F2 formulations, using chitosan and Carbopol 934P at ratios of 1:1 and 1.05:1 respectively, showed minimal drug release in the first hour (F1: 0.18%, F2: 0.37%). By 12 hours, cumulative release reached 98.00% (F1) and 93.94% (F2), indicating F1 had faster release. Both showed minimal release in the initial hours, followed by a significant increase after 6–7 hours. Drug release followed Peppas kinetics, indicating a diffusion-controlled mechanism.

CONCLUSION

The present investigation was carried out to develop colon specific drug delivery systems using chitosan and Carbopol 934P as a carrier for metronidazole as model drug compression coated tablets of metronidazole were prepared, the drug release studies were carried out in-vitro and chitosan and Carbopol in the form of compression-coat over metronidazole core tablet remains intact in physiological environment of stomach and small intestine in different ratios. The compression coated metronidazole tablet coated with chitosan: Carbopol in F1 formulations provided best degradation in simulated colonic fluids.

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