In-Vitro Evaluation Study of Extended Release Matrix Tablet of Ciprofloxacin and Amoxicillin

 

Avinash Jiddewar^1*, Dr. N. I. Kochar²

¹Research Scholar, P. Wadhwani College of Pharmacy, Yavatmal (M. S.)

²Professor, P. Wadhwani College of Pharmacy, Yavatmal (M. S.)

 

 

ABSTRACT:

A floating extended release formulation of a broad-spectrum antibiotics containing ciprofloxacin and Amoxicillin have been prepared by a unique blend of polymer (HPMC) matrix, NaHCO₃ (Sodium bicarbonate) and other excipients in a optimized ratio to achieve an extended or delayed drug release profile up to 12 hours without any chemical interaction between drug and excipients. A unique blend of polymer matrix has been made by two different grades (K4M-low viscosity and K15M-high viscosity) of 'hydroxypropylmethyl cellulose' (HPMC) in an optimized ratio of 1: 35.66 (HPMC K4M: HPMC K15M) to reach the targeted drug release profile. The in vitro dissolution study shows that the floating tablets are capable of drug release over a period of 12 hours. The treated data are fitted into various kinetic models and R² values are evaluated. The analysis shows that the drug release from the floating matrix followed Higuchi release kinetics more preferably. As the “n” (release exponent) values of Krosmeyer- Pappes model of most of the formulation batch are in the range of 0.5 – 0.89 and 0.89- 1.0.

 

 

 

1. INTRODUCTION:

Oral route is the most preferable and convenient route for drug administration to any other route of drug administration. Therefore, formulation scientists have been focusing on controlled release oral drug delivery systems for last few decades. So, the main aim is to prolong the time for drug administration from the small intestine. Oral dosage forms have to stay in-side the stomach or upper intestine for desired period of time so that entire drug can be released from the dosage forms.

 

Gastro-retentive systems confine the dosage forms for several hours in-side the stomach and considerably prolong the gastric residence time of drugs. Prolonged gastric retention improves bioavailability, reduces drug waste, and improves solubility for drugs that are less soluble in a high pH environment. It is also beneficial for local drug delivery to the stomach and proximal small intestines. Gastro retention helps to provide better availability of new products with new therapeutic possibilities and substantial benefits for patients^1-2.

 

Present Study was done to prepare the optimize formulation of Broad Spectrum Antibiotics containing Ciprofloxacin and Amoxicillin to Give Combination Treatment for multiple infection diseases. Mechanism of Action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination. Amoxicillin acts through the inhibition of cell wall biosynthesis that leads to the death of the bacteria.^3,4,5. As half-life of both drugs is very less which require the frequent administration. (Half-life of ciprofloxacin is 3.5 hrs whereas half-life of amoxicillin is only 1 hrs). Present Study was done to prepare the extended release matrix tablet of broad spectrum antibiotics to minimize the frequent administration of Tablet.

 

2. MATERIAL AND METHOD:

Ciprofloxacin and Amoxicillin was obtained as gift Sample from Anazeal Research Lab Mumbai, HPMC K4M, HPMC K15M was obtain from Mahalaxmi Chemicals, Hyderabad, Sodium bicarbonate, citric Acid and Mg Stearate was also obtained from Mahalaxmi Chemicals, Hyderabad. Other al chemicals used are of Analytical Grades.

 

3. EXPERIMENTAL DETAILS:

3.1 Methodology of the Experiment:

The project leads to a method for preparing an extended release tablet formulation of Ciprofloxacin and Amoxicillin. A unique blend of matrix system was used as a base for retarded release of drug. Two different grades of hydroxypropyl methyl cellulose (HPMC K4M and HPMC K15M) were mixed in different ratio to obtain a suitable matrix system for achieving the extended release profile of the said antibiotic^6,7. Statistical analysis was done by the help of Design Expert 8.0.0.0 software. There are three independable variables and six responses in the formulation designing process.

 

3.2 Preformulation Study:

Preformulation testing is the first step in the rational development of dosage forms of drug substances. It can be defined as an investigation of physical and chemical properties of a drug substance alone and when combined with excipients. The overall objective of reformulations testing is to generate information useful to the formulator in developing stable and bioavailable dosage forms that can be mass produced.

 

 

3.3 FTIR spectroscopic analysis:

3.4 Formulation Development:

Formulation was developed by using HPMC K 4 M to enhance the drug release, HPMC K 15M use for retarded release of drug useful for Extended release of Drugs from Tablet. NaHCO₃ (Sodium bicarbonate) is used in the tablet formulation of Antibiotics as a floating agent as well as to retain the tablet dosage form of Antibiotics by maintaining a optimized floating lag time (FLT) and total floating time (TFT) in the stomach, without disturbing the drug release profile. A fixed concentration of citric acid is used to increase the floating ability of Sodium bicarbonate^8-9.

 

 

3.5 Preparation of tablet formulation of the above-mentioned batches:

At first all ingredients (HPMC K4M, HPMCK 15 M, Drugs and NaHCO3) are mixed by geometric dilution. Citric acid is dissolved by 4 ml ethanol in a Petri-dish. Then the mixture is mixed with the citric acid associated with ethanol to prepare a kindle like mass. Then Granules are prepared by 16 mesh and subsequently followed by 24 mesh sieves. After that the granules are subjected to drying in hot air oven until 5% moisture retains. After optimum drying the prepared granules are ready for punch in tablet punching machine¹⁰.

 

Fig. 1. FTIR spectra of Ciprofloxacin

 

Fig. 2. FT-IR spectrum of Amoxicillin

 

Table: 1 Formulation Development

 

4. EVALUATION:

In-vitro Evaluation Studies:

Table 2: Evaluation of targeted parameters of prepared formulation batches for Ciprofloxacin and Amoxicillin:

Formulation Code	FLT (min)	TFT (hours)	CPR 2h (%)	CPR 4h (%)	CPR 8h (%)	CPR 12h (%)
	1	12	27.16	46.43	79.78	99.25
2	1	12	24.71	45.24	78.41	97.52
3	1	12	16.32	34.21	67.42	95.55
F	1.5	12	29.28	48.72	82.58	100.92
F	1.2	12	27.64	47.25	80.71	100.28
F	1.2	12	17.76	35.3	74.98	95.93
F7	1.5	12	29.37	48.72	82.34	100.52
F8	1.2	12	20.73	40.82	76.69	97.35
9	1.5	12	14.98	30.81	60.3	80.83
F10	1	12	27.15	46.04	79.77	99.28
F11	1	12	15.23	31.06	61.51	85.57
F12	1.5	12	18.34	36.73	76.07	96.23
F13	1.5	12	14.95	30.71	60.33	81.16
F14	1.2	12	15.79	33.77	65.42	92.55

 

Table 3: Regression analysis of release kinetic data

 

Figure 3 Drug release pattern of FI batch

 

Figure 4 Drug release pattern of F2 batch

 

Figure 5 Drug release pattern of F3 batch

 

Figure 6 Drug release pattern of F4 batch

 

Figure 7 Drug release pattern of F5 batch

 

Figure 8 Drug release pattern of F6 batch 

 

Figure 9 Drug release pattern of F7 batch

 

Figure 10 Drug release pattern of F8 batch

 

Figure 11 Drug release pattern of F9 batch

 

Figure 12 Drug release pattern of F10 batch

 

Figure 13 Drug release pattern of F11 batch

 

Figure 14 Drug release pattern of F12 batch

 

Figure 15 Drug release pattern of F13 batch

 

Figure 16 Drug release pattern of F14 batch

 

Figure 17 Drug release pattern of final optimized formulation

 

 

5. DISCUSSION:

The in vitro dissolution study shows that the floating tablets are capable of drug release over a period of 12 hours. The study shows that the floating tablets absorbed the water and got swollen. Initially a barrier gel layer forms around the tablet and the interior of the tablet remains dry. The drug diffuses through this barrier gel layer gradually erodes with time and release the drug. The study also showed that the HPMC K 4 M enhances the drug release, such as F1, F4, F5, F7, F10 batches. These batches containing high percentage of HPMC K 4M shows higher drug release than other formulation batches in the respect of same time profile. On the other hand batches (F9, F11, F13) containing high percentage of HPMC K 15M shows retarded release of drug. However the batch F11 shows the in-vitro drug release pattern, which is very closer to the targeted release pattern. The floating lag time (FLT) is inversely proportional to the concentration NaHCO₃ but the optimum floatability is obtained in the specified range of concentration of NaHCO₃. The dissolution data are treated and analyzed to understand the kinetic and mechanism of the drug release from the floating matrix tablet. The treated data are fitted into various kinetic models and R² values are evaluated. The analysis shows that the drug release from the floating matrix followed Higuchi release kinetics more preferably. As the “n” (release exponent) values of Krosmeyer- Pappes model of most of the formulation batch are in the range of 0.5 – 0.89 and 0.89- 1.0. So, t he release mechanism is non-fickian or anomalous transport leading to gradual erosion of matrix and to some extent Case- II transport mechanism. Comparing between Zero order and First order release pattern, Most of the formulation showed Zero order release than First order. So, release of drug from the formulationis is not concentration dependent, which is a principle criteria of an extended release dosage form.

 

6. CONCLUSION:

A floating extended release formulation of a broad-spectrum antibiotics have been prepared by a unique blend of polymer (HPMC) matrix, NaHCO₃ (Sodium bicarbonate) and other excipients in a optimized ratio to achieve an extended or delayed drug release profile upto 12 hours without any chemical interaction between drug and excipients. A unique blend of polymer matrix has been made by two different grades (K4M-low viscosity and K15M-high viscosity) of 'hydroxypropylmethyl cellulose' (HPMC) in a optimized ratio of 1: 35.66 (HPMC K4M: HPMC K15M). to reach the targeted drug release profile (Table: 16) i.e, CPR2h(%), CPR4h(%), CPR8h(%), CPR12h(%) are respectively 15.00 %, 30.00 %, 60 % and 90 % are completely supported by the U.S.P guide line (U.S.P Edition- 2009, Volume: II, Pages: 1957, 1959 and 1961), NaHCO₃ (Sodium bicarbonate) is used in the tablet formulation of Antibiotics as a floating agent. Where NaHCO₃ helps to retain the tablet dosage form of Antibiotics by maintaining a optimized floating lag time (FLT) and total floating time (TFT) in the stomach, without disturbing the drug release profile. Other excipients such as citric acid and magnesium stearate are used in the formulation. Magnesium stearate is used as lubricant in optimum concentration which does not affect the desirable release of drug. A fixed concentration of citric acid is used to increase the floating ability of Sodium bicarbonate. The weight variation, content uniformity, thickness and hardness test and friability of the final optimized formulation are within the specified limit of U.S.P. On that basis by using optimized formulation, we can formulate the sustained release floating formulation.

 

7. REFERENCES:

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Received on 01.07.2017       Modified on 09.09.2017

Accepted on 26.09.2017     ©A&V Publications All right reserved