PREPARATION AND EVALUATION OF RAPIDLY DISSOLVING TABLETS OF RALOXIFENE HYDROCHLORIDE BY TERNARY SYSTEM FORMATION

  • Gamal Mohamed El Maghraby Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, Egypt
  • Samar Fayez Ghanem University of Tanta

Abstract

Objectives: Enhancing the dissolution rate of raloxifene hydrochloride for the preparation of rapidly disintegrating tablets with subsequent rapid dissolution.

Methods: Binary and ternary solid dispersions (SDs) with different carriers were prepared at various drug: carrier ratios including cremophor RH 40, polyvinylpyrrolidone (PVP K30), poloxamer 407 and gelucire 44/14 as carriers and were evaluated by drug content, In-vitro dissolution studies, Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) analysis analysis. The most efficient solid dispersion was selected for preparation of rapidly dissolving tablets.

Results: SDs showed enhanced dissolution rate compared to the unprocessed drug. Differential scanning calorimetry revealed that enhancement in drug dissolution was mainly due to a change in its crystalline structure. FTIR studies revealed no interaction between the drug and excipients. The dissolution pattern of the drug from the prepared tablet depended on the components of the tablets with those containing a combination of super-disintegrants (crospovidone and croscarmellose) in the presence of citric acid as channeling agent and pH modifier being the best.

Conclusion: The study presented a system capable of increasing the dissolution rate of raloxifene with successful incorporation in rapidly disintegrating tablets with subsequent fast dissolution.

 

34
Keywords: Raloxifene hydrochloride, Binary solid dispersion, Ternary solid dispersion, Raloxifene dissolution rate, Rapidly dissolving tablets

Downloads

Download data is not yet available.

Author Biographies

Gamal Mohamed El Maghraby, Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta, Egypt
32
Samar Fayez Ghanem, University of Tanta
35

References

1. Hochner-Celnikier D. Pharmacokinetics of raloxifene and its clinical application. Eur J Obstet Gynecol Reprod Biol 1999;85:23‒9.
2. Lippuner K, Buchard PA, De Geyter C, Imthurn B, Lamy O, Litschgi M, et al. Recommendations for raloxifene use in daily clinical practice in the swiss setting. Eur Spine J 2012;21:2407–17.
3. Agnusdei D. Clinical efficacy of raloxifene in postmenopausal women. Eur J Obstet Gynecol Reprod Biol 1999;85:43–6.
4. Kastelan D, Giljevic Z, Kraljevic I, Korsic M. Selective estrogen receptor modulators: A possible new treatment of osteoporosis in male. Med Hypotheses 2006;6:1052–3.
5. Gielen E, Vanderschueren D, Callewaert F, Boonen S. Osteoporosis in men. Best Pract Res Clin Endocrinol Metab 2011;25:321–35.
6. Thakkar H, Nangesh J, Parmar M, Patel D. Formulation and characterization of lipid-based drug delivery system of raloxifene-microemulsion and self-microemulsifying drug delivery system. J Pharm Bioallied Sci 2011;3:442–8.
7. Cubitt HE, Houston JB, Galetin A. Prediction of human drug clearance by multiple metabolic pathways: integration of hepatic and intestinal microsomal and cytosolic data. Drug Metab Dispos 2011;39:864–73.
8. Keshavarz A, Karimi-Sabet J, Fattahi A, Golzary AA, Rafiee-Tehrani M, Dorkoosh FA. Preparation and characterization of raloxifene nanoparticles using rapid expansion of supercritical solution (RESS). J Supercrit Fluids 2012;63:169–79.
9. El-Maghraby GM, Alomrani AH. Synergistic enhancement of itraconazole dissolution by ternary system formation with pluronic F68 and Hydroxypropyl methylcellulose. Sci Pharm 2009;77:401–17.
10. Oh MJ, Shim JB, Yoo H, Lee GY, Jo H, Jeong SM, et al. The dissolution property of raloxifene Hcl solid dispersion using hydroxypropyl methylcellulose. Macromol Res 2012;20:835–41.
11. Tran TH, Poudel BK, Marasini N, Woo JS, Choi HG, Yong CS, et al. Development of raloxifene-solid dispersion with improved oral bioavailability via spray-drying technique. Arch Pharm Res 2013;36:86–93.
12. Suthar AK, Solanki SS, Dhanwani RK. Enhancement of dissolution of poorly water soluble raloxifene by preparing nanoparticles. J Adv Pharm Educ Res 2011;2:189–94.
13. Jha RK, Tiwari S, Mishra B. Bioadhesive microspheres for bioavailability enhancement of raloxifene hydrochloride: formulation and pharmacokinetic evaluation. AAPS Pharm SciTech 2011;12:650–7.
14. El-Sheikh MA, Elnaggar YSR, Gohar EY, Abdallah OY. Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal. Int J Nanomed 2012;7:3787–802.
15. Kim AR, Lim SJ, Lee BJ. Metabolic inhibition and kinetics of raloxifene by pharmaceutical excipients in human liver microsomes. Int J Pharm 2009;368:37–44.
16. Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol 1975;27:48–9.
17. Pabari RM, Jamil A, Kelly JG, Ramtoola Z. Fast disintegrating crystalline solid dispersions of simvastatin for incorporation into orodispersible tablets. Int J Pharm Invest 2014;4:51–9.
18. British Pharmacopoeia. Seventh edition. Consistency of Formulated Preparations. London: British Pharmacopoeia Commission; 2013.
19. British Pharmacopoeia. Seventh edition. Friability. London: British Pharmacopoeia Commission; 2013.
20. European Pharmacopoeia Supplement 4.1. Council of Europe; European Directorate for the Quality of Medicine, Strasbourg, Tablets Monograph 0478; 2002.
21. Shaikh S, Khirsagar RV, Quazi A. Fast disintegrating tablets: an overview of formulation and technology. Int J Pharm Pharm Sci 2010;2:9–15.
22. El-Maghraby GM, Elsergany RN. Fast disintegrating tablets of nisoldipine for intra-oral administration. Pharm Dev Technol 2014;19:641–50.
23. Burraa M, Jukanti R, Janga KY, Sunkavalli S, Velpula A, Ampati S, et al. Enhanced intestinal absorption and bioavailability of raloxifene hydrochloride via lyophilized solid lipid nanoparticles. Adv Powder Technol 2013;24:393–402.
24. Nabi-Meibodia M, Vatanara A, Najafabadi AR, Rouinia MR, Ramezani V, Gilani K, et al. The effective encapsulation of a hydrophobic lipid-insoluble drug in solid lipid nanoparticles using a modified double emulsion solvent evaporation method. Colloids Surf B 2013;112:408–14.
25. Liu L, Wang X. Improved dissolution of oleanolic acid with ternary solid dispersions. AAPS PharmSciTech 2007;8:E113.
26. Ha NS, Tran TT, Tran PH, Park JB, Lee BJ. Dissolution-enhancing mechanism of alkalizers in poloxamer-based solid dispersions and physical mixtures containing poorly water-soluble valsartan. Chem Pharm Bull (Tokyo) 2011;59:844–50.
27. Goddeeris C, Van den Mooter G. Free flowing solid dispersions ofthe anti-HIV UC 781 with poloxamer 407 and a maximum amountof TGPS 1000: investigating the relationship between physicochemical characteristics and dissolution behavior. Eur J Pharm Sci 2008;35:104–13.
28. El-Gizawy SA, Osman MA, Arafa MF, El Maghraby GM. Aerosil as a novel co-crystal co-former for improving the dissolution rate of hydrochlorothiazide. Int J Pharm 2015;478:773‒8.
29. Sethia S, Squillante E. Solid dispersion of carbamazepine in PVP K30 by conventional solvent evaporation and supercritical methods. Int J Pharm 2004;272(1-2):1–10.
30. Roni MA, Dipu MH, Kibria G, Rahman H, Rony MDR, Jalil RU. Dissolution enhancement of poorly soluble carbamazepine by using polymeric solid dispersions. Int J Pharm Sci Res 2011;2:49–57.
31. Ibrahim MA, El-Badry M. Formulation of immediate release pellets containing famotidine solid dispersions. Saudi Pharm J 2014;22:149–56.
32. Bandela JJ, Anupama CH. Advanced PEGylation for the development of raloxifene hydrochloride, BCS Class II Drug. J Young Pharm 2009;1:306–11.
33. Sammour OA, Hammad MA, Megrab NA, Zidan AS. Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion. AAPS Pharm Sci Tech 2006;7:E55.
34. Parmar KR, Shah SR, Sheth NR. Studies in dissolution enhancement of ezetimibe by solid dispersions in combination with a surface adsorbent. Dissolution Technol 2011;8:55–61.
35. Nep EI, Conway BR. Preformulation studies on grewia gum as a formulation excipient. J Therm Anal Calorim 2012;108:197‒205.
36. Kunasekaran V, Krishnamoorthy K. Compatibility studies of Rasagiline mesylate with selected excipients for an effective solid lipid nanoparticles formulation. Int J Pharm Pharm Sci 2015;7:73–80.
37. Perdue JD, Seaton PJ, Tyrell JA, DeVido DR. The removal of cremophor EL from paclitaxel for quantitative analysis by HPLC-UV. J Pharm Biomed Anal 2006;41:117‒23.
38. Rai VK, Rajput BS, Sharma M, Agarwal A, Gupta A, Singh N. Solubility Enhancement of poorly water-soluble drug (Raloxifene Hydrochloride) by using different hydrophilic binders in solid dosage form. Pharmacie Globale 2010;3:120‒3.
39. Tran TH, Poudel BK, Marasini N, Woo JS, Choi HG, Yong CS, Kim JO. Development of raloxifene-solid dispersion with improved oral bioavailability via spray-drying technique. Arch Pharmacal Res 2013;36:86–93.
40. Patel PV, Panchal SS, Mehta TA. Improvement of dissolution rate of tacrolimus by solid dispersion technique. J Pharm Invest 2013;43:45–53.
41. Tallury P, Randall MK, Thaw KL, Preisser JS, Kalachandra S. Effects of solubilizing surfactants and loading of antiviral, antimicrobial, and antifungal drugs on their release rates from ethylene vinyl acetate copolymer. Dent Mater 2007;23:977–82.
42. Liao JB, Liang YZ, Chen YL, Xie JH, Liu WH, Chen JN, et al. Novel patchouli alcohol ternary solid dispersion pellets prepared by poloxamers. Iran J Pharm Res 2015;14:15–26.
43. Abd Alaziz DM, Sammour OA, Elshamy AA, Neseem DI. Formulation and evaluation of binary and ternary solid dispersions of domperidone by solvent evaporation method. Afr J Pharm Pharmacol 2014;8:66–80.
44. Parmar KR, Shah SR, Sheth NR. Preparation, Characterization and in vitro evaluation of Ezetimibe Binary Solid Dispersions with Poloxamer 407 and PVP K30. J Pharm Sci Innovation 2011;6:107‒14.
45. Patel SK, Solanki AB, Parikh JR. Enhancement of rate of dissolution of fenofibrate by ternary solid dispersion. J Pharm Cosmetol 2010;1:1–11.
46. Ahuja N, Katare OP, Singh B. Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers. Eur J Pharm Biopharm 2007;65:26–38.
47. Yamashita K, Nakate T, Okimoto K, Ohike A, Tokunaga Y, Ibuki R, et al. Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int J Pharm 2003;267:79–91.
48. Kumari R, Chandel P, Kapoor A. Paramount role of solid dispersion in enhancement of solubility. Indo Global J Pharm Sci 2013;3:78–89.
49. Al-Obaidi H, Buckton G. Evaluation of griseofulvin binary and ternary solid dispersions with HPMCAS. AAPS PharmSciTech 2009;10:1172–7.
50. Sinha S, Ali M, Baboota S, Ahuja A, Kumar A, Ali J. Solid dispersion as an approach for bioavailability enhancement of poorly water-soluble drug ritonavir. AAPS PharmSciTech 2010;11:518–27.
51. El-Maghraby GM, Alomrani AH. Effect of binary and ternary solid dispersions on the in vitro dissolution and in-situ rabbit intestinal absorption of gliclazide. Pak J Pharm Sci 2011;24:459–68.
52. Dey P, Maiti S. Orodispersible tablets: a new trend in drug delivery. J Nat Sci Biol Med 2010;1:2–5.
53. Tuladhar MD, Carless JE, Summers MP. The effects of polymorphism, particle size and compression pressure on the dissolution rate of phenylbutazone tablets. J Pharm Pharmacol 1983;35:269‒74.
Statistics
673 Views | 4141 Downloads
How to Cite
Maghraby, G. M. E., and S. F. Ghanem. “PREPARATION AND EVALUATION OF RAPIDLY DISSOLVING TABLETS OF RALOXIFENE HYDROCHLORIDE BY TERNARY SYSTEM FORMATION”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 1, Nov. 2015, pp. 127-36, https://innovareacademics.in/journals/index.php/ijpps/article/view/9160.
Section
Original Article(s)