ENHANCING DISSOLUTION RATE OF INDOMETHACIN BY IN SITU CRYSTALIZATION; DEVELOPMENT OF ORALLY DISINTEGRATING TABLETS

  • Nadia H. Naiem College of Pharmacy, University of Tanta, Pharmaceutical Technology Department, Tanta University, Egypt
  • Ebtessam A. Essa College of Pharmacy, University of Tanta, Pharmaceutical Technology Department, Tanta University, Egypt
  • Gamal M. Elmaghraby College of Pharmacy, University of Tanta, Pharmaceutical Technology Department, Tanta University, Egypt

Abstract

Objective: The main objective of this study was to investigate the potential of in situ crystallization of indomethacin, in presence or absence of hydrophilic materials, to improve drug dissolution with the goal of developing fast disintegrating tablets.

Methods: Indomethacin crystals were prepared by bottom up approach. Water containing hydrophilic additive (polymer or/and surfactant) was added to ethanolic solution of indomethacin while stirring. The selected polymers were hydroxylpropylmethyl cellulose E5 (HPMC E5), polyethylene glycol 6000 (PEG6000) and polyvinylpyrrolidone K40 (PVP K40). The surfactants used were Tween80 and Glucire 44/14. The precipitated particles were collected and air dried. Solid state characterization were performed in addition to in vitro release studies in both acidic (0.1 N HCL) and alkaline medium (phosphate buffer pH 6.8). Optimized formulation was selected to develop fast disintegrating tablets.

Results: Thermal behavior suggested modulation in crystalline nature with reduction in particle size that was confirmed by X-ray diffraction results. Infrared spectroscopy excluded any interaction between drug and hydrophilic excipients. Drug dissolution in acid media showed slight improve in drug release, while marked increase was observed in the alkaline media. Combination between Tween80 and HPMC (F7) showed the best dissolution parameters with 5-folds enhancement in release efficiency (RE) compared to pure drug. Formula F7 was successively used to formulate fast disintegrating tablets with prompted release of 58% of the loaded dose and RE of 83%.

Conclusion: In situ crystallization of indomethacin is a good approach for enhanced dissolution rate with the presence of hydrophilic additives during precipitation process improving the efficiency.

Keywords: In situ crystallization, Enhance solubility, Indomethacin, Fast disintegrating tablets

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References

1. Shailendra K, Dina NM, Rishab J, Pankaj S. Fast disintegrating combination tablets of omeprazole and domperidone. Asian J Pharm Clin Res 2009;2:74-82.
2. Vogt M, Kunath K, Dressman JB. Dissolution enhancement offenofibrate by micronization, cogrinding and spray-drying: comparisonwith commercial preparations. Eur J Pharm Biopharm 2008;68:283-8.
3. Kulkarani U, Patil BS, Hariprasanna RC, Borgaonkar PA, Hogade MG. Formulation and development of fast dissolving meloxicam tablets by solid dispersion technique. Int J Curr Pharm Res 2010;2:82-5.
4. Essa EA. Enhancement of carvedilol dissolution: surface solid dispersion versus solid dispersion. Asian J Pharm 2015;8: 283-9.
5. Elkordy AA, Tan XN, Essa EA. Spironolactone release from liquisolid formulations prepared with Capryol™ 90, Solutol® HS-15 and Kollicoat® SR 30 D as Non-volatile liquid vehicles. Eur J Pharm Biopharm 2013;83:203-23.
6. Saurabh SS, Issarani R, Nagori BP. Formulation and evaluation of self-emulsifying drug delivery system of etoricoxib. Asian J Pharm Clin Res 2017;10:367-72.
7. Balata GF, Essa EA, Shamardl HA, Zaidan SH, Abourehab MAS. self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol. Drug Des Dev Ther 2016;10:117-28.
8. Sunday AS, Simon C. Particle engineering techniques for inhaled biopharmaceuticals. Adv Drug Delivery Rev 2006;58:1009–29.
9. Yohei K, Koichi W, Manabu N, Shizuo Y, Satomi O. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications. Int J Pharm 2011;420:1–10.
10. Rasenack N, Muller BW. Dissolution rate enhancement by in situ micronization of poorly water-soluble drugs. Pharm Res 2002;19:1894-900.
11. Xia D, Quan P, Piao H, Piao H, Sun S, Yin Y, et al. Preparation of stable nitrendipine nanosuspensions uing the precipitation-ultrasonication method for enhancement of dissolution and oral bioavailability. Eur J Pharm Sci 2010;40:325-34.
12. Park MW, Yeo SD. Antisolvent crystallization of carbamazepine from organic solutions. Chem Eng Res Design 2012;90:2202–8.
13. El Kordy AA, Jatto A, Essa EA. In situ controlled crystallization as a tool to improve the dissolution of glibenclamide. Int J Pharm 2012;428:118-20.
14. Essa EA, Elmarakby A, Donia A, El Maghraby GM. Controlled precipitation for enhanced dissolution rate of flurbiprofen: development of rapidly disintegrating tablets. Drug Dev Ind Pharm 2017;24:1-10.
15. Lobenberg R, Amidon GL. Modern bioavailability: bioequivalence and biopharmaceutics classification system: new scientific approaches to international regulatory standard. Eur J Pharm Biopharm 2000;50:3-12.
16. Al Saidan SM, Alsughayer A, Eshra AG. Improved dissolution rate of indomethacin by adsorbents. Drug Dev Ind Pharm 1998;24:389-94.
17. Sinha B, Muller RH, Moeschwitzer JP. Bottom Up approaches for preparing drug nanocrystals: formulation and factors affecting particle size. Int J Pharm 2013;453:126-41.
18. United States Pharmacopiae National Formulary 24, United States Pharmacopial Convention, Rockville, MD; 2000.
19. Jain CP, Naruka PS. Formulation and evaluation of fast dissolving tablets of valsartan. Int J Pharm Pharm Sci 2009;1:219–26.
20. Bettinetti GP, Sorrenti M, Rossi S, Ferrari F, Mura P, Faucci MT. Assessment of solid-state interactions of naproxen with amorphous cyclodextrin derivatives by DSC. J Pharm Biomed Anal 2002;30:1173-9.
21. Otsuka M, Kato F, Matsuda Y, Ozaki Y. Comparative determination of polymorphs of indomethacin in powders and tablets by chemometrical near-infrared spectroscopy and x-ray powder diffractometry. AAPS PharmSciTech 2003;4:1-12.
22. Balata G, Shamardl H. Controlled crystallization as a tool to enhance the dissolution and anti-inflammatory properties of indomethacin. J Pharm Res 2012;5:4175-81.
23. El-Badry M, Fetih G, Fathy M. Improvement of solubility and dissolution rate of indomethacin by solid dispersions in gelucire 50/13 and PEG4000. Saudi Pharm J 2009;17:217–25.
24. Arafa MF, El-Gizawy SA, Osman MA, El Maghraby GM. Sucralose as Co-Crystal Co-former for hydrochlorothiazide: development of oral disintegrating tablets. Drug Delivery Ind Pharm 2016;42:1225-33.
25. Shirke SH, Shete AS, Doijad RC. Enhancement of dissolution rate of indomethacin by Kollicoat IR based solid dispersions. Der Pharm Lett 2015;7:64-73.
26. Essa EA, Balata GF. Preparation and characterization of domperidone solid dispersion. Pak J Pharm Sci 2012;25:783-91.
27. El Maghraby GM, Alomrani AH. Synergistic enhancement of itraconazole dissolution by ternary system formulation with pluronic F68 and hydroxypropylmethyl cellulose. Sci Pharm 2009;77:401–17.
28. Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol 1975;27:48-59.
29. Nokhodchi A, Javadzadeh Y, Siahi-Shadbad MR, Barzegar-Jalali M. The effect of type and concentration of vehicles on the dissolution rate of poorly soluble drug indomethacin from liquisolidcompacts. J Pharm Pharmacol Sci 2005;8:18–25.
30. Wen H, Morris KR, Park K. Study on the interactions between polyvinylpyrrolidone (PVP) and acetaminophen crystals: partial dissolution pattern change. J Pharm Sci 2005;94:2166–74.
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Naiem, N. H., E. A. Essa, and G. M. Elmaghraby. “ENHANCING DISSOLUTION RATE OF INDOMETHACIN BY IN SITU CRYSTALIZATION; DEVELOPMENT OF ORALLY DISINTEGRATING TABLETS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 10, no. 5, May 2018, pp. 18-23, doi:10.22159/ijpps.2018v10i5.24311.
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