Abstract
Ciprofloxacin is a fluoroquinolones antibiotic used for the treatment of IBD and specific complication of Crohn’s disease. Ciprofloxacin inhibit M. fortuitum, M. kansaii and M. tuberculosis. Ciprofloxacin is effective for the treatment of prostatitis caused by sensitive bacteria. Oral dose in adults are 250-750mg. Plasma half life of ciprofloxacin is 3-5 hr. The short biological half-life of drug (3-5 hours) also favors development of a sustained release formulation. The present study done by using various mucoadhesive polymers for preparation of mucoadhesive tablets. Various approaches to combine hydrophilic (HPMC, SCMC, tragacanth and sodium alginate) and hydrophobic (ethyl cellulose) polymers have been made to prepare total seven formulations. Further, these formulations were subjected to different evaluation studies like content uniformity, surface pH, friability, wash-off and dissolution tests. All the tests were performed using standard methods. Results for in vitro drug release and wash-off studies suggest that the formulation (F7) containing tragacanth and HPMC has shown better mucoadhesive property. Other studies have shown satisfactory results in all seven formulations. Thus, the present investigation suggests the combination of HPMC and tragacanth, as hydrophilic polymers for preparation of Ciprofloxacin mucoadhesive tablets.
Introduction
Antibiotics can be used as either adjunctive treatment along with other medications for active IBD, treatment for a specific complication of Crohn’s disease, or prophylaxis for recurrence in postoperative Crohn’s disease. Ciprofloxacin is an antibiotic which is used most frequently1. The fluorinated 4-quinolones, such as ciprofloxacin is orally effective for the treatment of a wide variety of infectious diseases and have relatively few side effects. Ciprofloxacin, inhibit M. fortuitum, M. kansasii, and M. tuberculosis. Oral doses in adults are 250–750 mg every 12 hours for ciprofloxacin. Bioavailability of the fluoroquinolones exceeds 50% for all agents and 95% for several. The serum half-lives range from 3 to 5 hours for ciprofloxacin. Ciprofloxacin is effective for the treatment of prostatitis caused by sensitive bacteria. Fluoroquinolones administered for 4–6 weeks appear to be effective in patients not responding to trimethoprim and sulfamethoxazole2 Controlled release means give sustained action along with its predictability and reproducibility of release of medicaments from the drug delivery system3. The mucoadhesive drug delivery system is more reliable than traditional drug delivery systems. Mucoadhesion, an interfacial phenomenon, is based on two materials, one of which is mucus layer of mucosal tissue to which the drug is held together by means of interfacial forces for prolonged period of time. Control release system ensures localization of drug in a particular site to improve and increase the bioavailability. The contact time is also enhanced due to interaction between polymers and mucus lining of tissue for sustained action4. Advance polymer systems in controlled delivery systems maintain the release rate as well as the concentration in the biological system by increasing its localization and avoiding first pass metabolism5.mucoadhesion as a means of influencing the duration of contact of medicinal formulations with mucous membranes immediately became a subject of interest to technologists6.
Materials and Methods
Ciprofloxacin (Ind-Swift Ltd., Parwanoo), HPMC, SCMC, tragacanth, magnesium stearate and talc (Central drug house, New Delhi), acacia (Nice chemicals Pvt Ltd, Cochin) and sodium alginate (Qualikems fine Chemicals Pvt. Ltd., New Delhi) were employed in the present study. All other chemicals were of analytical grade and were freshly prepared.
1. Method of preparation of ciprofloxacin mucoadhesive tablets
Mucoadhesive tablets each containing 250 mg of Ciprofloxacin were prepared by conventional wet granulation method using different mucoadhesive materials as given in Table 1. A batch of 100 tablets was prepared in each case a blend of 25 gm of Ciprofloxacin with required amount of polymers and required amount of diluents which were then granulated along with a solvent blend of water and ethyl alcohol (1:1). Firstly the required quantity of drug & polymer taken in a motor and pestle for trituration. Then the solvent is added drop wise with continuous stirring until the wet mass is formed. Then the wet masses were passed through 12 mesh sieve and wet granules were dried at 60º C for 4 hours. The dried granules (20 mesh) after blending with talc (0.5 gm) and magnesium stearate (0.5 gm) in a laboratory cube blender for 5 mins were compressed into 500 mg tablets of hardness 7-8 kg/sq.cm on a tablet compression machine. The tablets were then considered for further study7.
2. Evaluation of mucoadhesive formulation:
i. Weight Variation Test:
Weight variation test was done by weighing 20 tablets individually, the average weight was calculated and % variation of each tablet was calculated. Hardness and friability of the mucoadhesive formulations were evaluated using Monsanto hardness tester and Roche friabilator respectively.
ii. Drug Content uniformity:
The tablets were kept in 100 ml volumetric flask containing HCl pH 1.2 for 24 h. When tablets were completely dissolved the solution was centrifuged. After centrifuged the supernatant was collected. Absorbance was measured spetrophotometrically at 276 nm. Dilution was made using HCl (pH 1.2) as per requirment8.
iii. Surface pH:
A combined glass electrode was used for determination of surface pH. The tablets were kept in contact with 5 ml distilled water pH 6.5 ± 0.5 for 2 h in 10 ml beakers. The tablets swell up and pH was noted by bringing the electrode near the surface of the formulation after equilibrating for 1 min9.
iv. Wash-off test:
The mucoadhesive properties of the tablets were evaluated by an in vitro, wash-off method. Pieces of stomach mucosa of goat were mounted on the glass slides provided with suitable support. After fixing of 2 tablets to this glass slide, it was tied to the arm of USP tablet disintegration test apparatus and was run at 37oC. Time of detachment of both tablets was noted down10.
v. In vitro drug release study:
The in vitro drug release study was performed using USP dissolution rate test apparatus (paddle type; 50 rpm). Dissolution study was carried out for 12 h. HCl (pH 1.2; 900 ml) was used as dissolution media. Samples of each 5 ml were withdrawn after every 1 h for a period of 12 h. Volume in dissolution vessel was kept constant by equal replacement with fresh media. The samples were collected in test tubes after filtration through Watt Mann filter paper. The amount of the drug in the aliquots was quantified by taking the absorbance of the sample at 276 nm spectrophotometrically, using HCl pH 1.2 as the blank.
Results and Discussion
The prepared mucoadhesive tablets were evaluated for various physical parameters such as weight variation, hardness, friability and drug content. All the batches were produced under conditions to avoiding processing variables. The %loss in weight was between 0.25-0.79% and hardness of tablets ranged from 6.9-8.2 kg/cm2 and as shown in Table 2, is with in limit of IP. The content uniformity of the medicaments in the mucoadhesive tablets was within the range from 96.49 -104.81% as shown in table no 3.
The surface pH study for different formulations were within the range from 6.7-7.4 as shown in table no 4.
The release of Ciprofloxacin from the mucoadhesive tablets was studied by plotting cumulative percentage drug release vs time as shown in fig 1.The release rate was found to be decreasing as the concentration of polymer is increased. In the present study the formulation F7 has shown cumulative percent drug release of about 80.762% in 12 h as shown in fig 1.
Conclusion
The present study concludes that formulation F7 (containing Ciprofloxacin with HPMC and tragacanth) has given better drug release property than the other seven formulations and the wash-off test has shown that F7 has better mucoadhesive property.
References
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