Formulation and Evaluation of Colon Targeted Drug Delivery System of Mesalamine Using Wet Granulation

 

Ashish Y. Pawar, Rahul A. Ahirrao*

M.G.V’S Pharmacy College, Panchavati, Nashik- 422003. India

 

ABSTRACT:

Mesalamine is Anti-inflammatory drug used for the treatment of inflammation of bowel i.e. ulcerative colitis and chron’s disease. In the present study an attempt is made to formulate colon targeted drug delivery system of mesalamine using Eudragit S100 and HPMC K100 as a release retarding polymers. Various formulations were developed by varying concentration of Eudragit S100 and HPMC K100 by using wet granulation technique. The developed formulation were coated using thin layer of Eudragit S100 as a pH dependent polymer which starts to dissolves above pH 7 and  releases drug at the site of action and protects the tablet from releasing drug in stomach and intestine. The 3² factorial design were used to formulate various formulations of Mesalamine. Developed formulation were evaluated for various parameters like hardness, friability etc. The formulation F9 was found to be optimum based on all evaluation parameters. Also the optimized formulation is found to be stable for 3 months and doesn’t change its colour, shape, release pattern.

 

 

 

INTRODUCTION:

Colon is a site where both local and systemic delivery of drug can take place. Local delivery allows topical treatment however directly targeting drug into colon increase the effectiveness of drug and reduces its systemic side effect. Targeted drug delivery into colon is highly desirable for treatment of variety of bowl disease such as Ulcerative colitis, Chron’s disease, amebiosis, colonic cancer and systemic delivery of proteins and peptide drugs. In past few decades pharmaceutical scientist are extensively investigating the area of colonic region for targeted drug delivery system. The advent of slow release technologies increase the chances for drug to be released in colon^1-4.

 

Mesalamine is used as anti-inflammatory agent having half-life of five to seven hours with protein binding capacity of 20-30.When mesalamine is administered orally as a tablet it is rapidly and almost completely absorbed but  less amount of  drug is  reaching the distal small intestine and colon. Orally administered mesalamine act within the lumen of inflamed bowel and is partly absorbed into systemic circulation.

 

To prevent proximal small intestinal absorption and allow mesalamine to reach the inflamed bowel or colon the present approach is to formulate mesalamine colon targeted drug delivery system to reach the drug in colon and to increase the drug release in colon^4-6.

 

Furthermore drug targeting to colon would prove useful intentional delayed drug absorption is desired from therapeutic point of view in treatment of disease that have peak symptoms in the early morning such as nocturnal asthma, angina or arthritis^7,8.

 

Colon-specific drug delivery system offers the following therapeutic advantages^6-9:

Reducing the adverse effects in the treatment of colonic diseases (ulcerative colitis, colorectal cancer, crohn’s disease etc.)

 

By producing the ‘friendlier’ environment for peptides and proteins when compared to upper gastrointestinal tract.

 

Minimizing extensive first pass metabolism of steroids.

Preventing the gastric irritation produced by oral administration of NSAIDS.

 

Delayed release of drugs to treat angina, asthma and rheumatoid arthritis. To achieve successful colon targeting it should overcome the following limitations.

 

The colon is also considered as “BLACK BOX” as most of the drugs are absorbed from upper part of GIT tract.

 

Advantages of CDDS over conventional drug delivery:

1)     Utilisation of drug is more.

2)     Side effects can be reduced.

3)     Lesser amount of dose is required comparatively.

 

Oral administration of different dosage form is the most commonly used method due to greater flexibility in design of dosage form and high patient acceptance. Rectal administration offers shortest route for the for targeting drug to colon, however reaching the proximal part of the colon via rectal route is difficult and it’s also uncomfortable for patients^10-12.

 

As absorption capacity of colon is very high which is attributed to the colon transit time, which can be as long as 20-35 hr, hence it is ideally suited for absorption. The absorption is influenced by the transport of water, electrolytes and ammonia across the mucus and it is more in proximal colon than the distal colon. Drug molecules pass from the apical to basolateral surface of epithelial cells by

·         Passing through colonocytes (transcellular transport)

·         Passing between adjacent colonocytes (Paracellular transport)

 

Small amphipathic drugs may pass this barrier through transcellular transport. However, transit through the cell cytoplasm may result in its extensive enzymatic extraction and degradation. Paracellular transport may be the most promising means of general drug absorption in colon. Since the membrane fluidity of proximal colonocytes is higher than distal colonocytes, drugs can easily pass via passive absorption process in the proximal colon. Additionally carrier mediated uptake of the drug in the colon is not extensive and usually related to metabolic events of resident bacteria. Receptor mediated endocytosis and pinocytosis could, however lead to transcellular transport of drug.

 

Mesalamine is an active ingredient of agents used for long term maintenance therapy to prevent chron’s disease and ulcerative colitis. However if only mesalamine is administered orally it will get absorbed in the GIT and does not reach the Intestine and hence it is important to reach the drug to the colon to give its action and hence the various approaches came^13-17,.

 

Factors to be considered in design of CDDS:

·         Physical properties of drug

·         Colonic residence time

·         Degradation by bacterial enzyme

·         Local physiological action of drugs

·         Diseased state

 

Some important factors are considered while developing CDDS as follows

 

Approaches Used In Site Specific Drug Delivery to Colon^4-9

1)    Primary approaches For CDDS-

a)     pH sensitive polymer coated drug delivery to the colon.

b)    Delayed release drug delivery to colon.

c)     Microbially triggered drug delivery to colon

i)      Prodrug approach

ii)     Azo-polymeric prodrugs

iii)    Polysaccharide based delivery systems

 

2)    Newly developed approaches for CDDS:

a) Pressure controlled drug delivery systems

b) Novel colon targeted delivery systems

c) Osmotic controlled drug delivery

 

3)    Chemical Approaches:

a)     Azo conjugate: The drug is conjugated via azo bond

b)    Cyclodextrin conjugates: The drug is conjugated with cyclodextrin

c)     Glycosidic conjugates: The drug is conjugated with glucoronate

d)    Glucoronide conjugate: The drug is conjugated with glucoronate

e)     Dextran conjugates: The drug is conjugated with dextran

f)     Polypeptide conjugates: The drug is conjugated with polypeptide

g)    Polymeric Prodrug: The drug is conjugated with polymer

 

Polymers used for site specific drug delivery to colon:

Polymers contain large number of structural units joined by some type of linkage form into chain like structure. These are nowadays used in formulating various pharmaceutical products. Naturally used polymers which include gummy exudates, proteins, enzymes, muscle fibres, polysaccharides. In olden days natural polymers are used but nowadays synthetic polymers come into industry.

a)       Natural Polymers – Guar gum, pectin, inulin, locust bean gum, cyclodextrins, dextran, chondroitin sulphate, boswellia gum, amylase, chitosan.

b)       Synthetic Polymers– Shellac, Ethyl cellulose, Cellulose acetate phthalate, hydroxypropyl methyl cellulose, Polyvinyl acetate phthalate, Eudragits, Hydroxy propyl methyl cellulose acetate succinate.

 

There are lots of polymers but currently Eudragit S100 is used widely as because of its pH dependent solubility as it dissolves at pH 7.0 which is also a pH of colon. Because of its pH dependent solubility it is used as an enteric coating agent which resist gastric fluid.

 

HPMC K100 is used in combination with Eudragit S100 to achieve more of the drug to release in the colon as because of its concentration used is 10-20% which is a tablet release retardant which helps to maintain the drug release for the long period of time^12,13.

MATERIALS AND METHODS:

Materials:

Mesalamine was a gift sample from BES chemicals ltd, Ankleshvar, India. Eudragit S100 was gifted by Evonik industries. HPMC K100 was obtained from colorcon Asia pvt. Ltd., Goa. MCC, DCP, Crosspovidone, Mg. sterate, Starch was obtained from Modern Science Nashik.

 

FORMULATION and DEVELOPMENT OF COLON TARGETED DRUG:

Factorial design:

From the literature survey studies the concentration of HPMC K100 and Eudragit S100 were selected. Based on concentration 2 factors will be evaluated, each at 3 levels, and experimental trials will be performed at 9 possible combinations which is given in Table No 1 and 2. The amount of HPMC K 100 and Eudragit S100 was selected as independent variables^18,19.

 

Table No. 1 :Factor Level

Polymers	-1	0	+1
HPMC K100	16%	17%	18%
Eudragit S100	6%	7%	8%

 

So the possible combination of two variables factors having three levels can be given as

 

Methods:

Preparation of tablet by wet granulation:

All ingredients were weighed separately. Accurately weighed quantity of drug, and polymers (Eudragit S100 and HPMC K100) are mixed thoroughly in mortar and granulated using 5% w/v starch solution as a binder as given in Table No 3.The granules so obtained are placed in oven at 60ºC for 2 hr. These granules are again passed through 22 mesh sieve after getting dry. The fine granules formed are then lubricated with 0.5% w/w Mg.sterate. The flow properties are determined. These granules were then compressed into tablet (each 600mg) using 11.7mm concave punch of 10 station shiv pharma ETBC 1974 compression machine. The prepared tablets were then coated with the Eudragit S100 solution coating^15,20,21.

 

Differential Scanning Calorimetry:

DSC analysis was performed using Shimadzu-Thermal analyser DSC 60on 2-5 mg samples. Samples were heated in an open aluminium pan at a rate of 10ºC/min conducted over a temperature range of 30 to 320ºC under a nitrogen flow of 2-bar pressure  thermo-gramof planedrug was compared with thermo-gram of polymer and drug mixture

 

X-ray diffraction study:

This study mainly based on the scanning of x-rays by crystals. By this method one can identify the crystal structure of various solid compounds. Powder method is used for the determination of crystalline structure of drug. Non crystalline portion simply scatters X-ray beam to give

 

a continuous background, while crystalline portion causes diffraction of X-ray gives diffraction lines that are not continue.An amorphous form does not produce a pattern. The X-ray to scatter in a reproducible pattern of peak intensities at distinct angle (2 Theta) relative to the incident beam. Each diffraction pattern is characteristics of a specific crystalline lattice for a given compound.

 

Approximately 100 mg of sample was exposed to Cu radiation wavelength 1.5406 A°, having  temperature rang 170 °C to +450 °C in a wide-angle powder X-ray diffractometer (Make/Model-Bruker AXS D8 Advance). The instrument was operated in the step-scan mode, in Max. Usable angular range is 3° to 135°.

 

The sample tablet or the formulation tablet were send for analysis to “SAIF STIC, COCHIN”

 

Scanning Electron Microscopy:

Scanning electron microscopy (SEM) is a method for high resolution surface imaging. The SEM uses an electron beam for surface imaging. SEM Make JEOL Model JSM - 6390LV having resolution 8 nm (Acc V 3.0 KV, WD 6 mm, SEI).

 

For this study pure mesalamine and a coated tablet was taken.The sample was observed under scanning electron microscope at 500X and 1500X resolution in “Saif Stic, Cochin

Table No. 2 :Factorial Design Calculations

Polymers	F1	F2	F3	F4	F5	F6	F7	F8	F9
HPMC K100	+1	+1	+1	0	0	0	-1	-1	-1
Eudragit S100	+1	0	-1	+1	0	-1	+1	0	-1

 

Table No. 3 : Formula and Contents

INGREDIENTS	FORMULATIONS (mg)
	F1	F2	F3	F4	F5	F6	F7	F8	F9
Mesalamine	250	250	250	250	250	250	250	250	250
HPMC K100	108	108	108	102	102	102	96	96	96
Eudragit S100	48	42	36	48	42	36	48	42	36
MCC PH102	53	59	65	59	65	71	65	71	77
DCP	108	108	108	108	108	108	108	108	108
Crosspovidone	30	30	30	30	30	30	30	30	30
Mg.sterate	3	3	3	3	3	3	3	3	3
Starch	q.s	q.s	q.s	q.s	q.s	q.s	q.s	q.s	q.s
TOTAL	600	600	600	600	600	600	600	600	600

 

Accelerated stability study:

Stability studies were carried out as per ICH, Q1 A guidelines. During the stability studies, the product is exposed to normal condition of temperature and humidity. The optimized mesalamine formulations were subjected for stability studies.

 

Stability Protocol:

a)       Packaging material:

The tablets were wrapped in aluminium foils.

b)       Storage condition:

 

The tablets were subjected to stability as per ICH guidelines in the following conditions. Samples were kept in a stability chamber. (Thermo lab, TH 2005)

 

c)       Stability storage condition:

 

Characterization of granules:

Bulk density: ^15,20,21,22

An accurately weighed quantity of powder is carefully poured into graduated cylinder. Then after pouring the powder into the graduated cylinder, the powder bed was made uniform without disturbing.

 

Then, the volume was measured directly from the graduation marks on the cylinder as ml. The volume measure was called as the bulk volume and the bulk density is calculated by following formula

 

Weight of sample in gm.

Bulk density (g/ml) =

Volume occupied by the sample

 

Tapped density: ^15,20-22

The measuring cylinder containing known mass of blend  was tapped for 100 tappings. The minimum volume occupied in the cylinder and weight of the blend as measured. The tapped density was calculated using the formula

 

Weight of sample in gm.

Tapped density (g/ml) =                                                           

                                 Volume occupied by the sample

Angle of repose: ^15,20,21,22

The angle of repose of the powder blend was determined by using funnel method. The accurately weighed powder was taken in a funnel. The height of the funnel was adjusted in such a way that the tip of the funnel just touched the apex of the heap of the powder. The diameter of the powder cone was measured and angle of repose was calculated by using the equation

Tan θ= h/r                                                                                            

Where, h and r are the height and radius of the powder cone.

 

 

Carr’s index: ^15,20-22

An important measure that can be obtained from bulk density determinations is the percent compressibility C, which is defined as follows

                                                ρ_{b -} ρ_u

                                 C =         ---------------

                                                     ρ_b

Hausner’s ratio: ^15,20-22

A similar index has been defined by Hausner’s

                     ρ_b

Hausners ratio = -------

                     ρ_u                           

 

Coating Solution:

An organic polymer solution consisting of 2.5% w/v Eudragit S100 in isopropyl alcohol and acetone solution in 1:1 ratio. Weighed quantity of polymer was dissolved in solvent in which good solubility by keeping it in on magnetic stirrer at 150-200 rpm. After the complete solubilisation of polymer Glycerine was added in solution as a plasticizer, talc as an anti- adherent in 5% w/w to prevent adhering of tablets during coating process and finally titanium dioxide in 0.05% w/w as an opacifier^21-23.

 

Coating of Tablet:

The coating of tablet was done by spray coating method. The tablets were placed in coating pan and the pan is rotated at a speed of 25-30 rpm and the air gun temperature was 50º, spray pressure 3kg/cm² and spray rate of 12ml/min. Coating solution is sprayed on the tablets as the coating pan rotates at a specific speed^21-23.

 

Calibration of Mesalamine in Respective Solvents:

 

Figure No 1 : Calibration curve of Mesalamine in 0.1 N HCl

 

Figure No 2 : Calibration curve of Mesalamine in pH 7.2 buffer

In vitro dissolution study was performed for mesalamine using USP apparatus II (paddle method) at 50 rpm, 37±0.5ºC and 900 ml of dissolution medium. In order to simulate pH changes along GIT, the dissolution medium with 0.1 N HCl, pH 6 buffer and pH 7.2 buffer as given in USP were prepared. When performing the in vitro release experiments 0.1 N HCl medium was first used for 2hr which was then replaced by fresh simulated intestinal fluid medium and kept for 1 hr. this medium was again replaced by simulated colonic fluid and kept for 4 hr. Samples were withdrawn at regular time intervals. Samples were estimated using UV/VIS spectrophotometer with λ_max231.8 and 330 nm (Shimadzu 2450 – double beam UV/VIS spectrophotometer) at respective wavelength Calibration curve of Mesalamine in respective solvents is given in Figure No 1 and 2^24-30.

 

RESULT AND DISCUSSION:

Preformulation study:

Characterization of granules:

Organoleptic properties:

The mesalamine was studied for organoleptic characters such as colour, odour and appearance. Results of organoleptic properties of the mesalamine were found to be similar as mentioned in literature, which is given in table No 4.

 

Table No 4 :Identification test for mesalamine drug

Identification test	Observed Result	Reported standard
Appearance	Slightly crystalline powder	Slightly crystalline powder
Colour	Pale Yellow	Pale yellow
Odour	Egg like Smell	Egg like smell

 

Melting point:

The melting point determined by capillary, thiels tube method. The results are shown in table No 5 and compared with standard.

 

Table No 5: Melting point of mesalamine

 

Solubility:

Solubility of the drug in various solvents is performed and results are shown in table No 6.

 

Table No 6: Solubility of Mesalamine in various solvents

 

UV-Vis Spectroscopy:

Table No 7 : Wavelength of maximum absorbance in different solvents

In UV spectroscopy study, the maximum wavelength of mesalamine in 0.1 N HCl and pH 7.2buffer was found to be 231.8 nm and 330 nm respectively. Reported λ max was found to be 230 nm and 332 nm as shown in table No 7and its graph is shown in figure No 3.

 

Figure No 3: UV-Vis Spectrum of Mesalamine in 0.1N HCl and pH 7.2 buffer

 

FTIR spectra of Mesalamine:

The FTIR spectrum of Mesalamine exhibited characteristic signals as shown in Figure No 4andtable No 8. The absorption bands shown by Mesalamine are characteristic of the groups present in its molecular structure. The presence of absorption bands corresponding to the functional groups present in the structure of Mesalamine and absence of well-defined unaccountable peaks is a confirmation of the purity of the drug sample.

 

 

Figure No 4 : FT-IR spectrum of pure drug Mesalamine

 

 

Table No 8 : Identification of functional groups in FTIR spectra of Mesalamine

 

Evaluation of granules

For the tablets to be fine evaluation of granules must be done which contains bulk density, tapped density, angle of repose, Hausner’s ratio, % compressibility which is given in table No 9.

 

In-vitro Drug release study –

The dissolution rate studies were performed to evaluate the dissolution character of the mesalamine from the colon targeted tablets. Figure 5 shows release profile of all batches. The dissolution study of all formulations shows the percentage drug release were found to beIn between 88% to 99% in within given time period. From the data F9 shows the faster drug release compare to any other batch and F1 batch shows the lowest drug release and hence F9 was considered as the best formulation based on its kinetic release characteristic. The cumulative % drug release of drug is given in table No 10.

 

As the polymers used are HPMC K100 and Eudragit S100 the Eudragit S100 as a pH dependent polymer it dissolves at pH 7 in colon and HPMC K100 as a tablet release retardant avoids the excessive release of the drug into the colon and hence the drug release in the colon for longer period.

 

Table No. 9 : Evaluation parameters of Granules

Formulation	Bulk density	Tapped density	Hausner’s ratio	% Compressibility index	Angle of repose
F1	0.434	0.5	1.150	13.06	28.20±0.48
F2	0.454	0.5	1.100	9.1	29.04±0.98
F3	0.416	0.5	1.200	16.68	27.88±0.32
F4	0.384	0.454	1.181	15.37	27.42±0.58
F5	0.50	0.625	1.25	20.00	28.44±0.31
F6	0.454	0.555	1.22	18.18	29.61±0.52
F7	0.454	0.555	1.22	18.18	29.61±0.52
F8	0.454	0.555	1.22	18.18	29.86±0.16
F9	0.50	0.625	1.22	18.18	29.74±0.33

 

The table given above shows the parameters and are within limits.

 

 

Table No. 10 : Cumulative % release of drug

	Cumulative % drug release
Time in (min)	F1	F2	F3	F4	F5	F6	F7	F8	F9
0	0±0.00	0±0.00	0±0.00	0±0.00	0±0.00	0±0.00	0±0.00	0±0.00	0±0.00
30	0±0.00	0±0.00	0±0.00	0±0.00	0±0.00	0±0.00	0±0.00	0±0.00	0±0.00
60	0±0.00	0±0.00	0.098±	0±0.00	0±0.00	0±0.00	0±0.00	0.083±	0±0.00
90	0.083 ±0.00	0.098 ±0.00	0.143 ±0.001	0.105 ±0.001	0.090 ±0.00	0.120 0.001±	0.098 ±0.00	0.120 ±0.001	0.105 0.001±
120	0.113 ±0.001	0.136 0.005±	0.158 ±0.001	0.166 ±0.00	0.143 ±0.001	0.188 ±0.002	0.151 ±0.003	0.166 ±0.004	0.196 ±0.06
150	0.157 ±0.001	0.190 ±0.002	0.103 ±0.004	0.201 ±0.007	0.114 ±0.003	0.179 ±0.008	0.206 ±0.005	0.136 ±0.009	0.174 ±0.02
180	0.223 ±0.001	0.288 ±0.013	0.206 ±0.006	0.304 ±0.007	0.295 ±0.011	0.332 ±0.022	0.321 ±0.012	0.288 ±0.060	0.288 ±0.022
210	5.510 ±0.001	5.897 ±0.011	5.455 ±0.01	5.704 ±0.011	5.648 ±0.010	6.174 ±0.019	6.008 ±0.008	7.280 ±0.058	7.888 ±0.026
240	11.63 ±0.77	12.63 ±0.41	12.18 ±0.29	14.84 ±0.41	13.35 ±0.59	15.51 ±0.60	17.39 ±0.56	17.90 ±0.64	17.08 ±0.50
270	17.18 ±0.83	17.91 ±0.55	17.18 ±0.40	22.41 ±0.31	20.41 ±0.42	21.60 ±0.62	22.61 ±0.48	23.35 ±0.76	25.50 ±0.67
300	24.78 ±0.40	31.16 ±0.21	26.17 ±0.98	31.51 ±0.43	30.64 ±0.85	29.85 ±0.52	34.80 ±0.62	35.66 ±0.98	36.84 ±0.65
330	44.51 ±0.52	53.07 ±0.38	44.15 ±0.76	48.66 ±0.62	44.30 ±0.92	46.05 ±0.84	49.01 ±0.46	50.43 ±0.86	49.36 ±0.51
360	71.55 ±0.82	71.01 ±0.59	70.40 ±0.68	72.42 ±0.52	71.66 ±0.57	72.05 ±0.62	73.49 ±0.45	73.32 ±0.35	77.49 ±0.62
390	80.18 ±0.55	79.31 ±0.65	80.07 ±0.46	80.73 ±0.38	79.03 ±0.63	81.74 ±0.72	83.91 ±0.43	82.47 ±0.79	81.71 ±0.86
420	90.17 ±0.57	89.46 ±0.89	90.84 ±0.58	92.72 ±0.50	90.55 ±0.62	91.41 ±0.95	94.72 ±0.63	93.15 ±0.45	97.74 ±0.63

 

Table No. 11 : Best Fit Model

Formulation	Zero order plot	First order plot	Hixon-Crowell plot	Higuchi plot	Korsemeyer -peppas plot
	Regression Coefficient (R²)				n value
F1	0.9689	0.9501	0.9455	0.8947	0.7971
F2	0.9759	0.9672	0.9693	0.9298	0.8448
F3	0.9659	0.9576	0.9504	0.8995	0.8022
F4	0.9726	0.9829	0.9700	0.9304	0.8454
F5	0.9716	0.9623	0.9613	0.9186	0.8294
F6	0.9845	0.9764	0.9593	0.9161	0.8267
F7	0.9734	0.988	0.971	0.933	0.8498
F8	0.9801	0.9683	0.9745	0.9377	0.8561
F9	0.9846	0.9628	0.967	0.9367	0.847

 

Figure No. 5: Comparative in-vitro release profile of all formulations

 

Maintaining the sink condition is important during the dissolution experiment for consistent and accurate measurement of the dissolution rate. Sink dissolution could be maintained throughout the dissolution study and drug solubility could not be a factor responsible for retardation of drug release from the formulation studied.

 

Mechanism of Drug Release:

From the in-vitro release study and the graph obtained from the release of drugs it states that all batches follows zero order except F4 and F7 batch which follows first order. The dissolution rate of batches F1 to F9 was fitted only to Zero order andFirst order model.The coefficient of determination (R²) value was used as criteria to choose best model to fit drug release from the tablets. The R² values of all models are given in above table. In almost all case the R² of zero order is higher than any other model indicating that the drug release from the formulation followed Zero order. The best fit model is given in table No 11.

 

Scanning Electron Microscopy:

Scanning electron microscopy carried out for checking uniformity of coating layer of optimized batch. The SEM of coated and uncoated tablet was carried out at 500X and 1500X. From SEM study Figure 6 and 7 indicates that tablets are uniformly coated.

 

Figure No. 6 : SEM of uncoated tablet F9 batch

 

Figure No. 7 : SEM of coated tablet F9 batch

 

X-RAY Diffraction study:

In this study pure drug sample represents the XRD and not having sharp intense peak. Peak shown in figure 8and its theta values are given in table 12. From theta value and intensity of peak it can conclude that drug having no crystalline nature. In other the mixture of polymer and drug after compression were used for XRD study. Peak shown in figure 9and its theta values are given in table 13.

 

Figure No.8 : X-RD of Mesalamine

Table No.12 : Φ value from XRD of Mesalamine

 

Figure No. 9: XRD of Mesalamine and polymer mixture after compression

 

Table No. 13: Φ Value of Mesalamine and polymer mixture after compression

 

The XRD study is done to represents the crystalline nature of the pure drug sample and their compression mixture which represents the crystalline nature of the drug.

 

The Figure 8 and 9 represents that the drug is not crystalline in nature as their peaks are not sharp so this indicates that the drug is non-crystalline in nature and the mixture sample also contains the same situation so this states that there is no change in the tablet after compression.

 

Accelerated stability study:

Accelerated stability testing of the tablet of the optimized batch F9 was subjected to evaluate for the physio-chemical parameters, for three month at 40ºC/ 75% RH. As shown in table 14. There is no change in the physio-chemical properties of the tablets except drug release slightly differ.

 

 

Table No 14 : Stability study of Mesalamine tablet

	Parameters	After one month observation	After two month observation	After three month observation
1	Physical appearance	No change	No change	No change
2	Weight variation (mg)	0.603±0.060	0.601±0.059	0.602±0.060
3	Thickness (mm)	5.60±0.15	5.55±0.15	5.53±0.15
4	Hardness (Kg/cm²)	8.33±0.57	8.25±0.57	8.19±0.57
5	Friability	0.223±0.0030	0.220±0.0030	0.218±0.0030
6	Drug content (mg/tab)	100.34±0.25	99.92±0.20	99.89±0.21
7	In-vitro Dissolution	97.68	97.39	97.07

 

 

Figure No 10 : Optimized batch stability model fit graph

 

Stability study indicates that dissolution of optimized F9 batch follows same Zero order with no visible changes in the appearance of the tablet at each month interval till the end of the storage period and there was a little change in all but it’s negligible which is shown in Figure No 10.As there was negligible change and no change in physical appearance it indicates that the development formulation was stable. Drug release of the tablet at each month interval matches as compared to the Optimised batch i.e. 97.68%, 97.39%, 97.07%.

 

ACKNOELEDMENT:

We are thankful to BES Chemicals Ltd., Ankleshvar, India for Mesalamine as a gift sample and Evonik Industry for Eudragit S100 as a gift sample.

 

CONCLUSION:

·         From the literature review it was concluded that the polymer Eudragit S100 can be used in the formulation and it also helps in releasing drug for prolong period.

·         Mesalamine complies with the parameters of its physio-chemical properties.

·         The varying concentration of HPMC K100 used retards the drug release.

·         The varying concentration of Eudragit S100 used also helps to retard the release of drug.

·         The drug excipient compatibility study for one month at 50ºC /75%RH did not show any changes in the physical properties.

·         The various polymers and excipients used in varying concentration showed a promising result.

·         The wet granulation method is suitable for the tablet formulation.

·         The Eudragit S100 coating gives a negligible drug release in the intestine which is considerable and releases drug in colon by dissolving above pH 7.

·         The XRD of the drug shows the drug is slightly crystalline in nature.

·         The SEM of the uncoated and coated tablet shows a desirable change.

·         The accelerated stability study of the drug show no changes in the colour, shape, drug release etc.

 

REFERENCES:

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Received on 30.08.2014          Modified on 05.09.2014

Accepted on 10.09.2014          © RJPT All right reserved