INTRODUCTION:

Suppositories are medicated solid bodies suitably shaped for rectal administration. Rectal drug delivery has a number of advantages such as reduced hepatic first pass elimination of high clearance drugs improved enzymatic drug stability, higher drug load, avoidance of gastric irritation associated with certain drugs in case of nausea, vomiting and when the patient is unconscious. Rectal route of administration is specifically useful for infants and children who have difficulty in swallowing oral medicine. Drug administered in suppository form can produce not only local effect but also systemic therapeutic action. Suppositories can be prepared by using lipophilic bases or by hydrophilic bases. These suppositories melt or dissolve in body fluids and release the drug Indomethacin, 1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl-acetic acid (1,2) a potent nonsteroidal antiinflammatory agent (NSAIA), has been used effectively in the management of moderate to severe rheumatoid arthritis, ankylosing spondilytis, osteoarthritis and acute gouty arthritis. Like other NSAIAs, indomethacin causes irritation, nausea, anorexia, gastric bleeding and diarrhoea when given orally(3–5).

Indomethacin (IM) is a well established analgesic, anti-inflammatory and anti-arthritic agent (6-12). However, it causes a number of side effects including the most frequent gastrointestinal actions (13-16).

MATERIAL AND METHOD:

The chemicals used in this study were pure drug indomethacin and polymers like PEG 400, PEG 6000 (Merck).

Preparation of standard stock solution

The stock solution (100µg/ml) of indomethacin was prepared by dissolving accurately about 10mg of drug in small volume of phosphate buffer 7.4 pH and the volume was making up to 100ml with phosphate buffer 7.4 pH to prepare standard stock solution.

Determination of λmax

Calibration curve of indomethacin was prepared with phosphate buffer 7.4 pH and λmax was found to be 207.7 nm.

Preparation of calibration curve

From the stock solution of indomethacin a series of dilutions ranging from 2-10 µg/ml were prepared. Absorbance of these solutions was measured at 207.7 nm wavelength and calibration curve was plotted between concentration and absorbance UV-Visible (Spectrophotometer-Shimadzu UV-1800). The maximum absorbance of indomethacin was observed at 207-210nm respectively.

Preparation of suppositories

Accurately weighed quantity of pure drug and PEG (400, 6000) were taken. Then PEG (400, 6000) was melted in china dish using heater. Then drug is then poured in to china dish. After complete mixing the mixture is poured in suppository mould and kept in refrigerator.

Table 1: Formulation table

Ingredients ( % w/w )	Quantity in mg (F1)	Quantity in mg (F2)
Indomethacin	10	10
PEG 6000	60	80
PEG 400	40	20

Evaluation of Indomethacin Suppositories

Prepared suppositories were evaluated for release characteristics from the moulds and the hardness was checked when pressed between thumb and index finger. All the suppositories (made by the respective bases and selected for further studies), were weighed and average weight was calculated. Then all the suppositories were individually weighed and the variation from the average was calculated. Liquefaction time of the suppositories was determined by the apparatus measures the time necessary for a suppository to liquefy under pressure similar to those found in the rectum in the presence of water at body temperature. A glass tube with a stricture was filled with distilled water to adjust below the mark of stricture and heated in water bath to a temperature of 37±0.5°. A suppository was introduced in the tube and carefully pushed down its length until it sets on the top of stricture with the help of glass rod. The glass rod was continued to rest of the suppository till it reached the stricture due to the melting of suppository. The time taken by the glass rod to reach the stricture was determined as the liquefaction time of the suppository.

In vitro drug release

In vitro release study was performed by using USP type1 rotating basket apparatus (Electrolab TDT- 08L) and modified continuous flow through bead-bed apparatus (fabricated in the laboratory). In the first method, dissolution medium was 500 ml mixed phosphate buffer pH 7.4. Rotation speed was controlled at 120 rpm while temperature was maintained at 37±0.5°. At specified time intervals, samples of 1 ml were withdrawn from the dissolution medium and that amount was replaced with fresh medium to maintain the volume constant. The absorbance of the diluted samples was measured at 207.7nm for indomethacin by using UV Visible spectrophotometer. The percentage drug release was calculated using an equation obtained from standard curve.

RESULTS AND DISCUSSION:

Fig 1: Standard calibration curve of indomethcin in phosphate buffer 7.4 pH

Evaluation of different formulations of indomethacin suppositories

Table 2: Evaluation of different formulations of indomethacin suppositories

Formulation

Hardness (kg/cm³)

Weight variation mg± SD

Drug content (%)

Liquefaction time min ±SD

2.9

0.91834±

1.117

7.45±0.01

0.9724±

0.637

8.00±0.01

Table 3: Comparative in-vitro dissolution study of different formulations of indomethacin suppositories

Time in hrs.	(F1)	(F2)
0	0	0
0.16	89.32	69.47
0.33	91.30	75.42
0.5	93.29	79.39
0.66	95.27	80.39
0.83	97.26	91.30
1	98.25	95.27

Figure 2: Comparative in-vitro dissolution study of different test formulations of indomethacin suppositories

CONCLUSION:

The indomethacin suppositories of different formulation were subjected to different evaluation parameters like hardness, weight variation, dissolution study, Liquefaction time which is shown in table no. 2. The hardness of suppositories was in the range which indicated good mechanical strength and ability to withstand physical pressure and stress. The weight variation was also in the range which is within limits and shows good resistance of suppositories to mechanical stress. The percent drug content of tablets was within permissible limits i.e. 81% to 93%. The prepared suppositories were also evaluated for their Liquefaction time and in-vitro drug release. The drug release profile of the different formulations was given in table 3 and figure 2. Based on the results it can be concluded that indomethacin suppositories can be prepared by utilizing two type of hydrophilic polymer that is PEG 6000, PEG 400 in different ratios and formulation (F1) gives fast drug release as compare to formulation (F2).

REFERENCES:

1. Borne RF. Nonsteroidal anti-inflammatory agents. In: Williams AD, Lemke LT, editors. Foye’s principle of medicinal chemistry. 5th ed. Lippincot William and Wilkins; 2002: 751–93.

2. Ajazuddin, Saraf S. Legal regulations of complementary and alternative medicines in different countries. Pharmacognosy Review .6 (12); 2012: 154-160.

3. Roberts II LJ, Morrow DJ. Analgesic-antipyretic and anti-inflammatory agents. In: Hardman JG, Limbird LE, Gilman AG, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 10th ed. New York: McGraw Hill; 2001:705–6.

4. Katzung BG, Furst DE. Nonsteroidal anti-inflammatory drugs: Disease-modifying antirheumatic drugs; Nonopoid analgesics; Drugs used in Gout. In: Katzung BG, editor. Basic and clinical pharmacology. 7th ed. Applenton and Lange; 1998: 588–9.

5. Das KP, Bhattacharya SK, Sen P. Pharmacology. B I Churchill Livingstone. 1995.

6. Tripathi KD. Essentials of medical pharmacology. 5th ed. Jaypee Brothers (P) Ltd Medical Publishers; 2003.

7. Osol A., in Remington's Pharmaceutical Sciences, Mack Publishing Co. Easton, Pennsylvania, 1985: l1-18

8. Giri TK, Verma S, Alexander A, Ajazuddin, Badwaik H, Tripathy M, Tripathi D.K. Crosslinked biodegradable alginate hydrogel floating beads for stomach site specific controlled delivery of metronidazole. FARMACIA. 61(3); 2013: 533-550.

9. Alexander A, Singh A. Herbal drugs used for the treatment of asthma: An overview. Int J Cur Biomed Phar Res. 1(2); 2011: 67-79.

10. Giri TK, Choudhary C, Alexander A, Ajazuddin, Badwaik H, Tripathy M, Tripathi D.K. Sustained Release of Diltiazem Hydrochloride from Cross-linked Biodegradable IPN Hydrogel Beads of Pectin and Modified Xanthan Gum. Indian Journal of Pharmaceutical Sciences. 75(6); 2013: 619-742

11. Ajazuddin, Giri, TK, Saraf, S, Saraf, S, Tripathi, DK. Approaches for breaking the barriers of drug permeation through transdermal drug delivery. Journal of Controlled Release. 164; 2012: 26-40.

12. Giri TK, Kumar K, Alexander A, Ajazuddin, Badwaik H, Tripathy M, Tripathi D.K. Novel Controlled Release Solid Dispersion for the Delivery of Diclofenac Sodium. Current Drug Delivery. 10; 2013: 435-443.

13. Hart, F. D. and Poardmen, R.L. "Indomethacin: A new Non-steroid Antiinflammatory Agent" Brit. Med. J., 2; 1973: 965-971.

14. Kelly, M. "Indomethacin: An Antirheumatic Drug" Lancet, 2; 1964: 474-475.

15. Lovgren, O. and Allender, E. "Side Effect of Indomethacin" Brit. Med.J., 1; 1964: 118.

16. Dewangan D, Kumar T, Alexander A, Nagori K, Tripathi DK. Pyrazole: Their Chemistry and Pharmacological Potentials: A Review. Review Article Current Pharma Research ISSN. 1(4); 2011: 369-377.

Received on 05.05.2016 Modified on 19.05.2016

Research J. Pharm. and Tech. 2016; 9(7):942-944.

DOI: 10.5958/0974-360X.2016.00181.5