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 Table of Contents  
ORIGINAL ARTICLE
Year : 2012  |  Volume : 1  |  Issue : 3  |  Page : 143-150

Formulation and characterization of colon specific drug delivery system of prednisolone


1 Department of Pharmaceutics, K.L.E. University's College of Pharmacy, Vidyanagar, Hubli, Karnataka, India
2 Research Student, Department of Pharmaceutics, K.L.E. University's College of Pharmacy, Vidyanagar, Hubli, Karnataka, India
3 Department of Pharmacognosy, K.L.E. University's College of Pharmacy, Vidyanagar, Hubli, Karnataka, India
4 Department of Pharmacy, Fenny Pharmacy, New Jersey, USA

Date of Web Publication15-Jan-2013

Correspondence Address:
Fatima Sanjeri Dasankoppa
Department of Pharmaceutics, K.L.E. University's College of Pharmacy, Vidyanagar, Hubli, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2278-0521.106084

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  Abstract 

Background: Enteric-coated systems are most commonly used for colonic drug delivery and constitute a majority of commercially available preparations for colon targeting. This pH variation in different segments of gastrointestinal has been exploited for colon-specific delivery. Coating the drug core with pH-sensitive polymers, these polymers are insoluble in acidic media, but dissolves at a pH of 6 or more, thereby providing protection to the drug core in the stomach and to some extent in the SI releasing the drug in the colon. Aim: The present study aimed to statistically optimize a colon-specific drug delivery system of prednisolone for the treatment of inflammatory bowel disease. Materials and Methods: A 3 2 full factorial design was used for optimization. The independent variables employed were amount of hydroxyethyl guar (HEG) and % CWG each at three levels. The dependent variables were % CDR at 5 hours, % CDR at 12 hours, and t50% (time required for 50% drug release). The tablets were prepared by the wet granulation method using novel guar gum derivative HEG as a polysaccharide. The formulated tablets were evaluated for weight variation, thickness, hardness, friability, drug content, and swelling index. The tablets were coated with 10% w/v solution of Eudragit L100 and Eudragit S100 (1:4) in IPA using 20% w/w triethyl citrate as plasticizer. The coated tablets were evaluated for in vitro dissolution studies in different pH media mimicking the transit of tablet from stomach to colon. Results and Conclusions: Differential scanning calorimetry studies showed no incompatibility of drug with other excipients. The optimized formulation F9 containing 30% HEG and 9% CWG showed 10.09% drug release after 5 hours (lag phase) and 60.76% drug release after 12 hours. Drug release was accelerated in the presence of rat caecal contents and indicated the degradation of polysaccharide by colonic microflora. The optimized formulation was subjected to an in vivo X-ray imaging study in albino rabbit to trace the movement and behavior of the tablet in gastrointestinal tract. A short-term stability study of the optimized formulation showed no significant changes in physical appearance, drug content, and in vitro dissolution profile when stored at 40 ± 2°C/75 ± 5% RH for 3 months. The designed system can be potentially used as a carrier for colon delivery of prednisolone by regulating drug release in stomach and small intestine.

Keywords: Colon, eudragit, hydroxyethyl guar, prednisolone, statistical design, statistical optimization


How to cite this article:
Dasankoppa FS, Patwa S, Sholapur H, Arunkumar G R. Formulation and characterization of colon specific drug delivery system of prednisolone. Saudi J Health Sci 2012;1:143-50

How to cite this URL:
Dasankoppa FS, Patwa S, Sholapur H, Arunkumar G R. Formulation and characterization of colon specific drug delivery system of prednisolone. Saudi J Health Sci [serial online] 2012 [cited 2020 Dec 4];1:143-50. Available from: https://www.saudijhealthsci.org/text.asp?2012/1/3/143/106084


  Introduction Top


Targeted drug delivery to the colon is highly desirable for local treatment of a variety of bowel diseases such as ulcerative colitis, Crohn's disease, amoebiasis, colonic cancer, local treatment of colonic pathologies, and systemic delivery of protein and peptide drugs. [1],[2]

Prednisolone (PD), a typical glucocorticoid, has been used for the treatment of IBD. However, PD is orally administered, a large amount of the drug is absorbed from upper gastrointestinal (GI) tracts and enters into the systemic circulation. This deteriorates the therapeutic efficacy of PD and causes systemic side effects, such as adrenosuppression, hypertension, osteoporosis, etc., Therefore, it is preferable for treatment of IBD to deliver the drug site specifically to colon. [3] Delivery of drugs to the receptors at a particular site has the potential to reduce side effects and to increase pharmacological responses. [4]

To achieve successful colonic delivery, a drug needs to be protected from absorption and the environment of the upper GI region and then be promptly release into the proximal colon. This might be achieved by the use of special drug delivery system (DDS) that can protect the drug during its transfer to colon. [5],[6] In general, colonic-release drug delivery systems are characterized by two release phases: The first phase in which little or no drug is released is called the lag time and is followed by the second phase in which the drug is completely released over a short period of time. [7]

The various approaches used for targeting the drugs to the colon include formation of a prodrug, multicoating time-dependent delivery systems, coating with pH-sensitive polymers, pressure-dependent systems, and the use of biodegradable polymers. Enteric-coated systems are most commonly used for colonic drug delivery and constitute a majority of commercially available preparations for colon targeting. [8] The pH of the gastrointestinal tract (GIT) is acidic in the stomach and increases in the small and large intestine. This pH variation in different segments of GI has been exploited for colon-specific delivery. Coating the drug core with pH-sensitive polymers e.g. Eudragit® (methyacrylic acid-methylmethacrylate copolymers) has been successfully used for colon drug delivery in Asacol® Salofalc® . These polymers are insoluble in acidic media, but dissolve at a pH of 6 or more, thereby providing protection to the drug core in the stomach and to some extent in the SI releasing the drug in the colon. [9]

It was, thus, hypothesized that targeted delivery of prednisolone through oral route would not only reduce systemic exposure of drug but would also help to circumvent limitations associated with i.v. route. Moreover, reduced systemic exposure would help to decrease side effects. It was also anticipated that minimal systemic exposure of drug achieved due to site-specific delivery of prednisolone to colon would lead to reduction in dose as well as the duration of therapy in comparison to conventional oral administration.

Natural polysaccharides are now extensively used for the development of solid dosage forms for delivery of drug to the colon. The rationale for the development of a polysaccharide-based delivery system for colon is the presence of high levels of polysaccharidases of microbial origin in the human colon. [5]

Hydroxyethyl guar is semi-synthetically derived from guar gum a natural polysaccharide derived from the seeds of Cyamopsis tetragonolobus, having molecular weight of approximately 1,000000, giving it a high viscosity in a solution. Due to its high molecular weight, it is metabolized in large intestine due to the presence of microbial enzymes. It is hydrophilic in nature and swells in cold water forming viscous colloidal dispersions or sols. This gelling property retards release of the drug from the dosage form as well as it is susceptible to degradation in the colonic environment. Hydroxyethyl guar is less susceptible to microbial contamination and also the due to its slow rate of hydrations, the release is retarded. [10],[11]

The present research work was aimed to formulate and characterize a colon-specific drug delivery system of prednisolone using hydroxyethyl guar as a polysaccharide and coated with Eudragit L100 and Eudragit S100 as coating polymers by the spray coating technique.


  Materials and Methods Top


Materials

Prednisolone was obtained as a gift sample from Sanofi Aventis, Goa, India. Hydroxyethyl guar was gifted by Encore natural polymers Pvt. Ltd., Gujarat. Eudragit L100 and Eudragit S100 were obtained from Evonik Degussa India Pvt. Ltd., Mumbai. Other materials, namely lactose, PVP K30, talc, magnesium stearate, triethyl citrate used, were of analytical grades.

Methods

Drug-excipients interaction studies

Drug-excipients interaction studies were performed by the Differential Scanning Calorimetry (DSC) method after exposing the physical mixture at 40 ± 2°C and 75 ± 5% RH (Stability chamber TH 90S thermolab, Mumbai) for 3 months and compared with the DSC thermogram of pure drug. [12],[13]

Experimental design

A 3 2 full factorial design was used for the optimization procedure. The studied factors (independent variables) were: amount of hydroxyethyl guar gum (X 1 ) and % coat weight gain (X 2 ), each at three different levels as mentioned in [Table 1]. The dependent variables were: % cumulative drug released at 5 th hour (Y 1 ), % cumulative drug released at 12 th hour (Y 2 ), and t90% (time required for 90% drug release) (Y 3 ). A total of nine experimental runs (F1-F9) and an extra check point formulation F10 were performed and the composition of tablets prepared on the basis of experimental design is shown in [Table 2].
Table 1: Experimental design: Factors and responses


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Table 2: Composition of prednisolone colon targeted formulations


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Preparation of guar-gum-based colon-targeted prednisolone tablets

Guar-gum-based colon-targeted prednisolone tablets were prepared by the wet granulation method using PVP K30 (5% w/v in IPA) as a binder. Lactose was used as diluent and a mixture of talc along with magnesium stearate at a 2:1 (w/w) ratio was used as a lubricant. Hydroxyethyl guar was sieved through sieve no. 60 and mixed with prednisolone (passed through sieve no. 16) and lactose (passed through sieve no. 60). The powders were blended and granulated with 5% w/v PVP K30. The wet mass thus obtained was passed through sieve no. 22 to obtain granules which were dried at 50°C for 2 hours. The dried granules were sieved through sieve no. 22/44 and blended with talc and magnesium stearate. The lubricated granules were then compressed into core tablets (average tablet weight 100 mg) by a 10 station rotary tablet machine (Rimek Mini Press-I) using concave punches. [14]

Coating of prednisolone core tablets

The prepared core tablets were coated with 10% w/v solution of Eudragit L100 and Eudragit S100 (1:4) in IPA using 20% w/w triethyl citrate as plasticizer. Tablets were coated using a tablet coating pan. The pan was rotated at the speed of 12 rpm and the coating solution was sprayed at a rate of 1 ml/min. Spraying pressure was maintained at 4 lb/cm 2 and inlet and outlet temperatures were kept at 40°C and 30°C, respectively. The process was continued until the required CWG was achieved. Thereafter, the tablets were dried using IR lamp mounted vertically on the tablet coating pan. [15]

Characterization of prednisolone tablets

Weight variation

Twenty tablets were randomly selected from each batch and weighed, the average weight was calculated, and then they were weighed individually to calculate standard deviation. [16]

Thickness

Thickness of the tablet was measured using Mitutoyo Digital Vernier caliper, Japan. Ten tablets of the formulation were picked randomly and measured individually. [16]

Hardness

The hardness of tablets was measured by the Monsanto hardness tester. For each batch, five tablets were used. [16]

Friability

Twenty tablets were weighed and placed in the Electrolab fibrilator USP Model EF1W, Mumbai and apparatus was rotated at 25 rpm for 4 minutes. The tablets were dedusted and weighed again. The percentage friability was calculated using the formula:

F = {1 - (W t/W)} ×100

where F = friability in percentage, W = initial weight of tablets, W t = weight of tablets after friabiation. The weight loss should not be more than 1%. [16]

Drug content

20 tablets were finely powdered and quantity of powder equivalent to 50 mg of prednisolone was accurately weighed and transferred in 100 ml volumetric flask containing 100 ml of methanol. The flask was shaken to solubilize the drug and the volume was made up to 100 ml with methanol. The solution was filtered through a 0.22 μm membrane filter and analyzed for drug content using a UV visible spectrophotometer at 242.8 nm.

Water uptake or swelling studies

The enteric coated tablets were weighed individually and separately placed in 50 ml of pH 7.4 phosphate buffer in a water bath thermostatically set at 37 ± 0.5°C. The tablets were removed at specified time intervals, blotted dry with filter paper, and weighed. The swelling index (SI) was determined using the relationship: (T a - T b/T b) × 100, where T a and T b are tablet weights after and before incubation at time t, respectively. [17]

In vitro drug release studies

In vitro
drug release studies were carried out using USP XXIII dissolution apparatus I (basket type). The dissolution medium consisted of 900 ml of pH 1.2 acid buffer (0.1N HCl) for first 2 hours and then it was transferred to pH 7.4 phosphate buffer for 3 hours (small intestinal pH) and then it was finally transferred to pH 6.8 phosphate buffer (colonic pH) for rest of the study. The temperature of the medium was set at 37 ± 0.2°C. The rotational speed was set at 50 rpm. 5 ml of sample was withdrawn at predetermined time interval of 1 hour up to 12 hours and same volume of fresh medium was replaced. The withdrawn samples were diluted to 10 ml with methanol, filtered, and analyzed at 242.80 nm using methanol as a blank. [17]

Validation of experimental design statistically

Polynomial equations were generated using design expert software version 8.0.6 (Stat-Ease, Inc, USA) for selected responses like % CDR at 5 th hour, % CDR at 12 th hour, and t90% . The generated polynomial equations were further reduced on the basis of significant terms obtained by applying ANOVA. The 3 2 full factorial design was validated by preparing an extra check point formulation (F10). The predicted values for % CDR at 5 th hour, % CDR at 12 th hour, and t90% for F10 were determined on the basis of respective polynomial equations, whereas the experimental values were determined by evaluating F10 for the selected dependent variables. The predicted and experimental values of the responses were compared for statistical significance using a paired t-test.

Selection of optimized formulation

Optimized formulation was selected on the basis of minimum % CDR at 5 th hour, minimum % CDR at 12 th hour, and maximum t90% and with good desirability.

Drug release studies in the presence of rat caecal content

To investigate the susceptibility of the prepared matrices for degradation by the enzymes produced by colonic bacteria, release studies were carried out in the presence of rat caecal content for the optimized formulation. Male Wistar rats weighing 110-125 g maintained on normal diet were used. Forty-five minutes before the commencement of drug release studies, six rats were killed by spinal traction, the abdomens were opened, and caecum was traced, ligated at both ends, dissected, and immediately transferred into phosphate buffer pH 6.8 previously bubbled with sterile nitrogen. These were finally added to the dissolution media to give a final caecal dilution of 4% (w/v). The entire procedure mentioned above was carried out under sterile nitrogen in order to maintain anaerobic conditions. [12]

In vivo X-ray imaging studies

The protocol for the in vivo X-ray imaging study was approved by the Institutional Animal Ethics Committee of KLE Society's College of Pharmacy, Hubli, India. As per the ref no. KLESCOPH/IAEC.Clear/2011-12/Ph.ceutics/06 albino rabbits were selected as an animal model for evaluating the colon-specific delivery system. Core tablets were prepared as per the optimized formula by replacing the drug with the radioopaque compound barium sulfate. Thereafter, the tablets were coated similarly to the optimized batch. All the rabbits used for the study were fasted overnight with free access to water. After an overnight fasting, the selected tablets were administered to the rabbits with 15 ml of water. X-ray images of the abdomen of the rabbits were taken at different time intervals to trace the movement and behavior of the tablet in the GIT of rabbits. [4]

Data analysis statistically by release kinetics

To analyze the mechanism of release and release rate kinetics of the dosage form, the data obtained were fitted into Zero order, First order, Higuchi matrix, Peppas and Hixon Crowell model using PCP-DISSO-V2 software. Based on the "R"- value, the best-fit model was selected. [18]

Stability studies for the optimized formulation

Stability studies of the optimized batch of prednisolone colon targeted tablets were carried out as per the ICH guidelines, at 40 ± 2°C/75 ± 5% RH for 3 months. The samples were observed for physical appearance, drug content, and in vitro drug release profile at the end of 1 month, 2 months, and 3 months.


  Results and Discussion Top


Drug-excipients interaction studies

Drug-excipients interaction studies were carried out using differential scanning calorimetry. It was found that melting endotherm of prednisolone was identical to endotherm of mixture of drug with excipients, indicating that prednisolone was compatible with other excipients used in the formulation in stressed conditions of 40°C/75% RH for 3 months. DSC thermograms are shown in [Figure 1].
Figure 1: DSC thermograms: (a) pure drug, (b) drug with excipients physical mixture exposed to 40°C/75% RH for 3 months

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Preparation of guar-gum-based colon-targeted prednisolone tablets

On the basis of 3 2 experimental design, nine formulations were prepared which were evaluated for weight variation, thickness, hardness, friability, drug content, and swelling index. The average weight of all the formulations ranged from 99.80 ± 1.356 mg in F9 to 100.70 ± 1.490 mg in F1. The thickness of tablets varied from 3.211 ± 0.012 mm in F5 to 3.219 ± 0.011 mm in F2. The hardness was found to be in the range of 5.06 ± 0.089 kg/cm 2 in F2 to 5.46 ± 0.114 kg/cm 2 in F9. The friability of all the formulation was found to be less than 1%. Drug content of all the formulation was found to be within the pharmacopoeial limits ranging from 98.092 ± 1.62% in F5 to 100.712 ± 0.96% in F9. The results of these investigations are shown in [Table 3].
Table 3: Physicochemical evaluation parameters of formulated core prednisolone tablets


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Swelling index or water uptake studies

A water uptake study was carried out in pH 7.4 phosphate buffer for 3 hours. The results show that swelling index increased with an increase in the concentration of HEG because of the hydrophilic nature of HEG. It was also found that as the CWG increased from 3% to 6% and finally to 9% swelling index decreased. The results are shown in [Table 3].

In vitro drug release

The release profile of all the formulations revealed no release in stomach environment (pH 1.2 acid buffer) showing that eudragit L100 and eudragit S100 act as good coating polymers which prevent the drug release in the stomach because of their higher threshold pH.

A comparative release profile of prednisolone from nine experimental formulations is shown in [Figure 2]. The results obtained from in vitro drug release studies showed that as the concentration of HEG increased from 10% (F1, F2, F3) to 20% (F4, F5, F6) and finally to 30% (F7, F8, F9), % CDR decreased. The reduction in the amount of with an increase in the amount of HEG can be explained on the basis of the fact that HEG tends to swell and form a gel at higher pH which might be contributing toward the decrease in the release profile owing to formation of a diffusion control layer. It was also found that at 3% CWG, the % CDR during lag period of 5 hours from formulation F1, F4, and F7 was found to be 26.11%, 24.02%, and 22.28%, respectively. As the CWG was increased to 6%, the % CDR from formulation F2, F5, and F8 was found to be 23.33%, 21.24%, and 16.36%, respectively. Further increasing the CWG to 9%, the % CDR from formulation F3, F6, and F9 was found to be 18.45%, 15.67%, and 10.09%, respectively. Hence, it could be seen clearly that as the CWG increased, the % CDR was found to be decreased.
Figure 2: Comparative release profile of prednisolone colon targeted formulations F1 to F9

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After evaluating the experimental formulations for their efficiency in preventing drug release in the gastric and small intestinal milieu, their release behavior in colonic environment was further analyzed using response surface methodology since it was desirable that the optimized formulation should exhibit minimum drug release in the stomach and small intestine and also in colon. Thus, the following parameters were selected as response variables for selection of final formulation. Y 1 : % CDR at 5 th hour; Y 2 : % CDR at 12 th hour; Y 3 : t50% (time required for 50% drug release) [Table 4].
Table 4: Experimental runs and observed results


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Statistical analysis

In order to determine the levels of factors (X 1 and X 2 ) which yielded optimum drug release responses, mathematical relationships were generated between the dependent and independent variables (responses) using Design expert software version 8.0.6. Following reduced equations were generated for the observed responses (Y 1 , Y 2 , and Y 3 ) after application of ANOVA.



In the above equations, coefficients with more than one factor represent the interaction between factors, while coefficients with second-order terms indicate a quantitative effect of independent variables (X 1 and X 2 ) upon the responses (Y 1 , Y 2 , and Y 3 ). As the concentration of HEG and % coat weight increased, the release at 5 th hour (Y 1 ) decreased and at 12 th hour (Y 2 ) as the concentration of HEG increased no significant effect was observed on the % drug release but as the % of coat weight increased there was a significant decrease in the drug release pattern and at T50% as the concentration of HEG and % coat weight gain increased there was a significant decrease in the release of the drug.

Analysis of variance indicated that assumed regression models were significant (P < 0.01) and valid for each considered response shown in [Table 5].
Table 5: Analysis of variance (ANOVA) of dependent variables


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The three-dimensional response surface plots were drawn to estimate the effect of the independent variables on each of the response as shown in [Figure 3]. Response surface plots depict a concurrent effect of any two variables on response parameter keeping one variable at a constant level.
Figure 3: Response surface plot showing effect of HEG and coat weight gain on: (a) percentage cumulative drug release at 5th hour, (b) percentage cumulative drug release at 12th hour and (c) t50%- Time taken for 50% drug release from the formulation

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Validation of experimental design

In order to check the validity of the generated equations in the optimization procedure, a new batch of tablets (extra check point formulation F10) was prepared. Comparative analysis of the predicted value and experimental values using paired t-test indicated no significant (P < 0.01) difference between the two values [Table 6], thereby establishing validity of the generated model.
Table 6: Predicted and experimental value of responses for extra check point formulation F10


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Selection of optimized formulation

Formulation F9 yielding desirability factor of 0.999 on analysis by design expert software version 8.0.6 was selected as the optimized formulation. The optimized formulation exhibited 10.09% of drug released after 5 hours, 60.76% drug released after 12 hours, and t50% (50% of drug released) at 10.74 hours.

In vitro dissolution study in presence of rat caecal contents

The optimized formulation F9 containing 30% HEG and 9% CWG with eudragit L100 and eudragit S100 (1:4) was subjected to drug release in the presence of 4% rat caecal contents in order to evaluate the susceptibility of prepared matrices to the colonic microflora. The results shown a significant drug release of 80.09% in the presence of rat caecal contents in comparison to 60.76% when same formulation tested in vitro in absence of rat caecal contents. An increase in drug release may be attributed to an increase in enzymes or bacterial population available for degradation of polysaccharide. A comparative drug release profile of optimized formulation F9 in the absence and the presence of rat caecal content is shown in [Figure 4].
Figure 4: Comparative drug release profile of optimized formulation F9 in the absence and the presence of rat caecal content

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In vivo x-ray imaging studies

Rabbits were selected as the animal model since variation in the pH of GIT of rabbits is analogous to that of humans. In vivo X-ray imaging allows the visualization of in vivo functioning of a colon-specific drug delivery system, thereby ascertaining the location of drug release. The results of X-ray imaging studies are shown in [Figure 5]. [Figure 5]b shows that the tablet remains intact in the stomach establishing in vivo efficiency of the coating of 10% w/v Eudragit L100 and Eudragit S 100 in preventing drug release in the gastric milieu. [Figure 5]c exhibits no significant difference in the integrity of tablet in comparison to [Figure 5]b, thereby indicating intactness of the tablet in small intestine. Reduction in size of tablet was seen in [Figure 5]d indicating release of drug in colon. These images clearly demonstrate that the optimized formulation F9 could be targeted specifically to the colon, without any premature drug release in the stomach and small intestine.
Figure 5: X-ray images showing in vivo behavior of optimized formulation F9 after oral administration to rabbit at: (a) 0 hour, (b) 2 hours in stomach, (c) 5 hours in small intestine, (d) 10 hours in colon

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Data analysis statistically

The curve fitting results of the release rate profiles for the designed formulations were subjected for data analysis using PCP-V2 dissolution software. It was found that all formulations were fitted to the Krosmeyers-Peppas model except F3 formulation which showed first-order release kinetics. Diffusion exponent (n value) for all formulations was found to be 0.7569 to 0.8896 (0.45 < n < 0.89); thus, all formulations followed the non-Fickian (anomalous) diffusion mechanism.

Stability studies

A stability study was performed for the optimized formulation F9 at 40 ± 2°C/75 ± 5% RH for 3 months. Drug content at the end of 1, 2, and 3 months was found to be 99.520 ± 1.82, 98.092 ± 1.48, and 96.664 ± 1.69, respectively, indicating no significant change in drug content. % CDR in 12 hours at the end of 1, 2, and 3 months was found to be 60.242 ± 2.62, 59.198 ± 1.94, and 57.805 ± 1.86, respectively. These observations indicated chemical stability of the drug and physical stability of the formulation during the storage period.


  Conclusion Top


Colon-targeted guar-gum-based tablets of prednisolone coated with Eudragit L100 and Eudragit S100 (1:4) were successfully prepared by the wet granulation technique and optimized using 3 2 full factorial design. DSC studies indicated compatibility of drug with other excipients. As the amount of HEG in the tablet formulations increases, the drug release decreases and as the percentage coat weight gain increases, the drug release also decreases. From the results of 3 2 full factorial design formulation F9 containing 30% HEG and 9% CWG evolved as optimized formulation and it released only 10.09% of drug in upper part of GIT. The accelerated stability studies established physical integrity of the formulation and chemical stability of the drug. The present study corroborates colonic delivery of prednisolone tablets dually coated with Eudragit L100 and Eudragit S100 (1:4) to be a potential system so as to restrict the release of drug to colon with the merits of reduced systemic exposure and enhanced potency.


  Acknowledgments Top


The authors are grateful Sanofi Aventis, Goa, India; Encore Natural Polymers Pvt. Ltd., Mumbai; Evonik Degussa India Pvt. Ltd., Mumbai for generous gift samples of prednisolone, hydroxyethyl guar, and Eudragit L100 and Eudragit S100 respectively.

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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