INTRODUCTION:

Controlled drug delivery systems can contain the upholding of drug levels within a suitable range, the need for fewer administrations, optimal use of the drug, and increased patient compliance. Oral controlled release (CR) formulations have been developed in an attempt to release the drug gradually into the GIT and uphold a stable drug concentration in the serum for longer phase of time. Such oral drug release devices have a restriction due to the gastric retention time (GRT), a physiological limitation.^{[1, 2]}

The floating system is intended to float in and over the gastric contents resulting in prolonged GRT. Furthermore, as the total gastrointestinal transit time of the dosage form is expand, by prolong the gastric residence time, these systems can also be used as sustained release procedure with a dense occurrence of administration and therefore, intensify patient conformity.^[3-5] Regrettably, floating devices administered in a single-unit form such as hydrodynamically balanced systems (HBS) are unreliable in prolonging the GRT owing to their ’all-or none’ evacuate procedure and, thus, they may cause high unpredictability, in bioavailability and local vexation due to a large amount of drug delivered at a specific site of GIT. In dissimilitude, multiple-unit particulate dosage forms have the edge that they pass uniformly through the GIT to circumvent, the quirk of gastric emptying and provide an adaptable release, thereby, reducing the inter subject variability in absorption and risk of local irritation. Different kinds of drug delivery systems for oral administration such as drug release rate-controlled delivery systems, time-controlled delivery systems and site-specific delivery systems have been broadly developed.^6-8 Controlled-release drug delivery systems (CRDDS) furnish drug release at a predetermined, predictable, and controlled rate. A major requisite for the successful performance of oral CRDDS is that the drug should have better absorption during the gastrointestinal tract (GIT), if possible by passive diffusion, to ensure constant amalgamation of the released drug. The average time necessary for a dosage unit to cross the GIT is 3–4 h, although insignificant variations exist among various dosage forms. Certain types of drugs can advantage from via gastro retentive strategy.^9,10The continuation of gastric residence time (GRT) is predictable to make the most of drug absorption from Floating Drug Delivery Systems (FDDS) due to augmented dissolution of drug and longer residence at the most positive sites of absorption. It is apparent from the current scientific and patent literature that an increased attention in novel dosage forms that are retained in stomach for a prolonged and predictable phase of time exists today in educational and industrial research groups.^11-13 One of the most practicable approaches for achieving a prolonged and expected drug delivery profile in the GI tract is to manage the gastric residence time. Gastro retentive Dosage Forms (GRDFs) will supply us with novel and significant beneficial options.^14,15 Thus control of placement of a DDS in a exact region of the GI tract offers plentiful advantages, especially for drug exhibiting an ‘absorption window’ in the GI tract. The real concern in the expansion of oral controlled release dosage forms is not just to extend the delivery of drugs for more than 12 hrs but also to extend the presence of dosage forms in the stomach or somewhere in the upper part of small intestine.^16-19 Alginate, a non-toxic biodegradable polysacharide obtained from naturally occurring brown algae have usual attention as a medium for controlled drug delivery. ^20-22Alginates can be measured as block polymers which mostly consist of mannuronic acid (M), guluronic acid (G) and mannuronic-guluronic (MG) blocks. Microencapsulation by ionotropic gelation is one of the broadly used methods for preparation of calcium-alginate microspheres/beads which has capability to form gels response with calcium salts. Newly the use of calcium-alginate gel beads as a vehicle for controlled drug delivery system has attracted considerable attention because of their possessions of re swelling which is vulnerable to environment pH.²³ consequently; acid sensitive drugs incorporated into beads would be protected from gastric juice. However, major disadvantages of alginate beads are their quick disintegration in simulated intestinal fluid and high porosity, which consequence in quick drug release.²⁴ Sodium alginate has been used as a matrix substance to accomplish controlled release drug delivery due to its hydrogel-forming properties. ^{25, 26}The alginate sodium salt forms thick solutions and gels when it come in to get in touch with with aqueous media. Due to this characteristic, the pharmaceutical industry has exploited the extensive attention in sodium alginate’s broad use as a carrier in hydrophilic matrix controlled and sustained release oral dosage forms.^27-29 Matrices incorporating alginate salts are employed to prolong the release of many drugs.³⁰ Ciprofloxacin hydrochloride was used as the model drug for the study, It has effective antibacterial activity against several pathogens particularly uropathogens and in the dealing of urinary tract infections.^31-33Extended-release formulation of ciprofloxacin provides systemic drug exposure which is comparable to that that achieved with twice-daily dosage form of conventional, immediate-release ciprofloxacin, with superior maximum plasma concentrations and less inter-patient unpredictability.^34-37 Hence, an effort was made to prepare a Sustained release (SR) dosage form of Ciprofloxacin hydrochloride micro beads of sodium alginate prepared by Emulsion gelation method for controlled release, which reduces the require for numerous dosing thereby growing patient conformity and declining the incidence of adverse effects. In the present study the beads prepared were evaluated with respect to particle size analysis, shape analysis, drug content, encapsulation efficiency and in vitro drug release.^38-40

MATERIALS AND METHODS:

Materials

Ciprofloxacin HCl was obtained as a gift sample from Mylan Lab Nashik (M.H.)

Preformulation

Preformulation studies for the selected drug Ciprofloxacin HCl include test for identification.^25,
30

Table 1: Preformulation of ciprofloxacin HCl

S.No.	Criteria	Character
1.	Colour	A pale yellow
2.	Taste	Slightly bitter in taste
3.	Odour	Odourless

Ciprofloxacin HCl was found to be faint to pale yellow crystalline powder. The taste of the ciprofloxacin HCL was slightly bitter in taste and odourless.

Preparation of 0.1N HCl (1.2) buffer solution

2.22 ml concentrated hydrochloric acid is dissolved in 250 ml distilled water, then check the pH at 1.2. Finally 0.1 N (1.2 pH) solution is prepared and used as a blank solution.

Quantitative estimation of drugs

UV spectrophotometric method was used to estimate the drug concentration in 0.1N HCl (1.2 pH)and Select the λ max at 275.40.

Determine the Wavelength of Maximum Absorbance in 0.1N HCl (1.2pH)

Ciprofloxacin HCl, 10mg was taken in upto 10ml 0.1N HCl in volumetric flask, sonicated for 10min to dissolve the sample. The prepared sample was 1000μg/ml. Than 1 ml of above solution was then transferred to another 10 ml volumetric flask and diluted it upto the mark with 0.1N HCl, This sample was 100μg/ml. The solution prepared was scanned in the range of 200 to 400 nm using 0.1N HCl as a reagent blank in UV spectrophotometer to the determine the λ max.

UV-Spectrophotometric Studies

The UV-Spectrophotometric Studies was done in photometric mode to set the wavelength 200-400 nm and measure the absorbance at 275.40nm.³⁰

Preparation of Calibration Curve

Table 2: Data for standard calibration curve of ciprofloxacin HCl in 0.1 N HCl

S.No.	Concentration (µg/ml)	Absorbance at 275.40 nm
1	2	0.077
2	4	0.130
3	6	0.158
4	8	0.211
5	10	0.252

Figure 1: Calibration curve of ciprofloxacin HCl in 0.1 N HCl

UV spectrophotometric study was carried out by using 0.1 N HCL as dissolution medium at the λ_max 275.40 nm. The range was found to 2–10 µg/ml and linearity was found 0.993. The λmax was determined by the scanning of the higher concentration i.e.10 µg/ml concentration solution. Than go photometric mode to set the wavelength and measure the absorbance at 275.40 nm. Standard curve was shown in fig 1.

Effect of sodium alginate concentration

Formulation F1 and F2 were prepared by 4% and 5% sodium alginate concentrations (w/v of alginate solution), respectively. In vitro drug release study was performed to observe the effect of sodium alginate concentration on Ciprofloxacin HCl release.

Effect of calcium chloride concentration

Formulations F-1 and F-2 were prepared by syringing the pre-gelation liquid in 1%, 2% and 3% CaCl₂ concentration (w/v) solutions, respectively. In vitro drug release study was performed to observe the effect of calcium chloride concentration on Ciprofloxacin HCl.

Method

Emulsion Gelation

Ciprofloxacin micro beads are prepared by emulsion gelation method. Sodium Alginate (4%) was dissolved in distilled demineralised water with agitation. Ciprofloxacin and different concentrations of mineral oil are added to the solution. This solution (2.5g) containing Ciprofloxacin (125 mg) and oil (0-40% (w/w)) is dropped through 21 G needle in to 1%calcium chloride (10 ml) and left at room temperature for 2 h. The resultant hydro gel beads are washed twice with distilled water and kept for drying at room temperature up to 12 hours.^26,27

Preparation and optimization of alginate gel beads

All alginate gel beads were prepared following the emulsion gelation procedure. A pre-gelation liquid was prepared by mixing sodium alginate solution and HPMC K100M by dissolving in water with stirring. Twenty millilitres of each of the pre-gelation liquid was then added, through a 26 G syringe (0.8 mm diameter, into 100 ml of different concentration [1% (w/v), 2% (w/v)] of CaCl₂ solution dropped from 5 cm dropping at the rate of 2 ml/min and kept for 20 min. The beads were then recovered from the CaCl₂ solution and washed with deionized (D.I.) water and air dried for 48 hours. Different formulations were prepared by varying the sodium alginate concentrations, calcium chloride concentrations and drug concentrations. The prepared formulations are given in table 3.^18,19

Table 3: Different formulations of alginate gel beads

FC	Amount of ciprofloxacin HCl (mg)	Amount of HPMC K 100 M (mg)	Amount of sodium alginate	Amount of calcium chloride
F1	250	250	4 %	1 %
F2	250	250	5 %	3 %

In-vitro drug release studies

The in vitro drug release studies of different formulation were conducted to ensure the effect of sodium alginate concentration and calcium chloride concentration and drug loading concentration on the release of ciprofloxacin HCL from the formulations. The dissolution studies were carried out using USP dissolution test apparatus 1 (basket method). The baskets of USP dissolution test apparatus 1, each containing 250 mg of ciprofloxacin HCL, were rotated at 50 rpm in 900 ml of 0.1 N HCL maintained at 37˚C±0.5˚C. An aliquot of 10 ml of the solution was withdrawn at predetermine time intervals and replaced by fresh dissolution medium. The withdrawn sample was analyzed in UV-spectrophotometer at λ max 275.40 nm.

Dissolution Profile

Table 4: Dissolution profile of F-1 Ciprofloxacin HCl beads

S.No.	Time (hr)	Absorbance	Concentration (µg/ml)	Amount (mg)	% Drug release
1.	0.5	0.277	13.1	118.7	47.48
2.	1	0.315	15	135	54
3.	2	0.330	15.7	141.4	56.5
4.	3	0.368	17.5	157.7	63.08
5.	4	0.371	17.9	161.5	64.6
6.	5	0.401	19.09	171.8	68.7
7.	6	0.410	19.5	175.7	70.28
8.	7	0.430	20.4	184.2	73.68

The dissolution profile of this formulation is gradually increasing the concentration with the time and after 7 hr. it shows 73.68% drug release.

Table 5: Dissolution profile of F-2 Ciprofloxacin HCl beads

S. No.	Time (hr)	Absorbance	Concent ration (µg/ml)	Amount (mg)	% Drug release
1.	0.5	0.286	13.6	122.5	49.02
2.	1	0.318	15.1	136.2	54.5
3.	2	0.343	16.3	147	58.8
4.	3	0.357	17	153	61.2
5.	4	0.377	17.9	161.5	64.08
6.	5	0.410	19.5	175.7	70.2
7.	6	0.501	23.8	214.6	85.86
8.	7	0.520	24.7	222.8	89.14

The dissolution profile of this formulation is gradually increasing the concentration with the time and after 7 hr. it shows 89.14% drug release.

CONCLUSION:

Ciprofloxacin HCl was found to be faint to pale yellow crystalline powder. The taste of the ciprofloxacin HCL was slightly bitter in taste and odourless. The solubility of ciprofloxacin HCL found in distilled water, 0.1 N HCL. The absorbance of ciprofloxacin HCl was determined by UV spectrophotometric method using UV visible spectrophotometer (shimadzu-1800). The λ_max of ciprofloxacin HCL in 0.1 N HCl was 275.40 nm. The standard curve of ciprofloxacin HCl was prepared in 0.1 N HCl in the concentration range of 2 to 10 µg/ml. A straight line with R² = 0.993 was found indicating that the ciprofloxacin HCl follows Beer’s law within the specified concentration range. The release profile shows that ciprofloxacin HCl released from beads in a considerable best during the initial hours of release. Concentration of sodium alginate increased from 4 to 5%, and the increase concentration of calcium chloride 1 to 3% in formulation the ciprofloxacin HCl was found to be release rapidly. The formulation F2 prepared in 3% CaCl₂ solution release ciprofloxacin HCl faster than the formulation F1 prepared in 1% CaCl₂ solution. The % drug release of formulation F2 was 89.14% and % drug release of formulation F1 was 73.68%. Thus, it can be concluded that this technique could be used for development of dosage forms.

ACKNOWLEDGEMENT:

The authors want to acknowledge the management and library of Rungta College of Pharmaceutical Sciences and Research, Kohka-Kurud road Bhilai, for providing necessary infrastructure and literature for the compilation of the work.

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Received on 03.05.2016 Modified on 02.06.2016

Research J. Pharm. and Tech. 2016; 9(7):848-852

DOI: 10.5958/0974-360X.2016.00160.8