Design expert assisted mathematical optimization of solubility and study of fast disintegrating tablets of Lercanidipine Hydrochloride
90% of drugs being researched today, posses poor solubility setback which inturn renders the drug with slower rate of absorption from the buccal route; hence dissolution is the rate limiting step for such lipophilic drugs. So, there is a need to keep a check on the dissolution profile of these drugs to ensure maximum therapeutic utilization. The dissolution rate therefore becomes a primary factor which governs the rate and extent of its absorption. Enormous work is being performed in the field of enhancement of solubility and dissolution behaviour of such drugs. Advancements and innovations have developed solid dispersion (SD) technique as the novel method for the solubility enhancement. Precision of dosing and patient's compliance is a crucial prerequisite for the management of chronic Antihypertensive treatment, So there arised a need to formulate a system which should resolve the difficulties associated with conventional tablets. This issue can be better tackled with the formulation of orally fast disintegrating tablets. The aim of the present study was to improve the solubility and dissolution rate of Lercanidipine hydrochloride (LRH) by formulating a solid dispersion with Polyvinyl pyrollidine (PVP-K30) and Guargum. Full Factorial designs are exploited to learn and research the effects of different variables on the quality determinant parameters. An appropriate statistical model was selected for the scrutiny of the enhanced dissolution pattern. Finally, these solid dispersions were incorporated into fast disintegrating tablets.
Keywords: Lercanidipine Hydrochloride, Solid dispersion, Statistical design approach, Melt fusion method, Fast disintegrating tablet, In vivo studies
2. Palmer AM. New horizons in drug metabolism, pharmacokinetics and drug discovery. Drug News Perspect. 2003; 16:57–62.
3. Serajuddin AT. Salt formation to improve drug solubility. Adv. Drug Deliv. Rev.; 2007; 59:603–616.
4. Jeffrey WM, Alvarez-Nunez A, Yalkowsky SH. Solubilization by cosolvents. Establishing useful constants for the log/linear model. Int. J. Pharm.; 2002; 245:153–166.
5. Chaumeil JC. Micronisation: a method of improving the bioavailability of poorly soluble drugs. Exp. Clin. Pharmacol.; 1998; 20:211–215.
6. Urbanetz NA, Lippold BC. Solid dispersions of nimodipine and polyethylene glycol 2000: Dissolution properties and physico-chemical characterisation. Eur J Pharm Biopharm.; 2005; 59:107-18.
7. Chen Y, Zhang GGZ, Neilly J, Marsh K, Mawhinney D, Sanzgiri YD. Enhancing the bioavailability of ABT-963 using solid dispersion containing Pluronic F-68. Int. J. Pharm.; 2004; 286:69–80.
8. Gohel MC, Patel LD. Processing of nimesulide–PEG 400–PG–PVP solid dispersions: preparation, characterization, and in vitro dissolution. Drug Dev. Ind. Pharm.; 2003; 29:299–310.
9. Hang Y, Myung-Kwan C, Hoo-Kyun C. Preparation and characterization of piroxicam/poloxamer solid dispersion prepared by melting method and solvent method. J. Korean Pharm. Sci.; 2007; 37: 1–5.
10. Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur. J. Pharm. Biopharm.; 2000; 50: 47–60.
11. Passerini N, Gonzalez-Rodriguez ML, Cavallari C, Rodriguez L, Albertini B. Preparation and characterization of ibuprofen–poloxamer 188 granules obtained by melt granulation. Eur. J. Pharm. Sci.; 2002; 15:71–78.
12. Passerini N, Albertini B, Perissutti B, Rodriguez L. Evaluation of melt granulation and ultrasonic spray congealing as techniques to enhance the dissolution of praziquantel. Int. J. Pharm.; 2006; 318:92–102.
13. Yu H, Chun MK, Choi HK. Preparation and characterization of piroxicam/ poloxamer solid dispersion prepared by melting method and solvent method. J. Korean Pharm. Sci.; 2007; 37: 1–5.
14. Patil MP, Naresh GJ. Preparation and characterization of gliclazide polyethylene glycol 4000 solid dispersions. Acta Pharm.; 2009; 59: 57–65.
15. Parmar N, Singla N, Amin SN, Kohli K. Study of cosurfactant effect on nanoemulsifying area and development of lercanidipine loaded (SNEDDS) self nanoemulsifying drug delivery systems. Colloids Surf B Biointerfaces; 2011; 86: 327–338.
16. Mukne AP, Nagarsenker MS. Triamterene _ cyclodextrin systems: preparation, characterization and in vivo evaluation. AAPS.; 2004; 5: 19–24.
17. Tayade P, Modi A. A comparative solubility enhancement profile of valdecoxib with different solubilization approaches. Indian J Pharm Sci.; 2007; 69: 274-278.
18. Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today; 2007; 12: 1068-1075.
19. Satomi O, Hideyuki S, Kumiko O, Yohei K, Takahiro M, Kayo Y. Improved dissolution and pharmacokinetic behavior of cyclosporine A using high-energy amorphous solid dispersion approach. Int J Pharm.; 2010; 399: 94-101.
20. Sambamoorthy U, Madanmohan K, Rohitreddy T, Someshear K, Kumaraswamy D. Formulation of sustain release solid dispersions of verapamil hydrochloride us¬ing ethyl cellulose and eudragit-Rspo. Int J Pharm Pharm Sci.; 2011; 3: 116-22.
21. Dinge A, Nagarsenker M. Formulation and evaluation of fast dissolving films for delivery of triclosan to the oral cavity. AAPS Pharm Sci Tech.; 2008; 9: 349-56.
22. Xingwang Z, Ningyun S, Baojian W, Yi L, Tianzheng G, Wei W. Physical charac¬terization of lansoprazole/PVP solid dispersion prepared by fluid-bed coating technique. Powder technol.; 2008; 182: 480-485.
23. Veerendra R, Pankaj R, Surender G, Harish D, Gitika A, Manju N. Formulation and characterization of solid dispersion of glimepride through factorial design. Iran J Pharm Sci.; 2011; 7: 7-16.
24. Seoung W, Min-soo K, Jeong-soo K, Hee Jun P, Sibeum L, Jong-soo w. Preparation and characterization of simvastatin/hydropropyl-β-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process. Eur J Pharm Biopharm.; 2007; 66: 413-21.
25. Khan S, Kataria P, Nakhat P, Yeole P. Taste masking of ondansetron hydrochloride by polymer carrier system and formulation of rapid-disintegrating tablets. AAPS Pharm Sci Tech.; 2007; 8: (E1-E7).
26. Ganesh MC, Pramod GY, Ashok VB, Sharwaree RH. Effect of some physical parameters and crospovidone on directly compressed frusemide tablets. Asian J Pharm.; 2008; 6: 235-40.
27. Vemula SK, Veerareddy PR. Fast disintegrating tablets of flurbiprofen: Formulation and characterization. Lat Am J Pharm.; 2011; 30: 1135-41.
28. Shoukri RA, Ahmed IS, Shamma RS. In vitro and in vivo evaluation of nimesulide lyophilized orally disintegrating tablets. Eur. J. Pharm. Sci.; 2009; 73: 162–71.
29. Subhash PG, Dinesh BM, Ravikumar M. 2012. Assessment of Lercanidipine Hydrochloride for Transdermal Delivery: Physiochemical, in-vitro and ex-vivo Characterization of Matrix type Lercanidipine Hydrochloride Transdermal Patches. Int. J. Pharm. Biol. Sci.; 2012; 3: 349-365
30. Sri J, Bhikshapathi DVRN. Formulation, development, and in vivo evaluation of mouth dissolving films containing palonosetron HCL. Int. J. Drug Deliv.; 2016; 8: 23–36.
31. Zeng F, Wang L, Zhang W, Shi KZ, Ong L. Formulation and in vivo evaluation of oral disintegrating tablets of clozapine/HydroXypropyl-Beta-cyclodextin inclusion complexes. AAPS PharmTech.; 2013; 14: 854–860.
32. Chavez-Eng CM, Constanzer ML, Matuszewski BK. Simultaneous determination of Aprepitant and two metabolites in human plasma by high-performance liquid chromatography with tandem mass spectrometric detection. J. Pharm. Biomed. Anal.; 2004; 35: 1213–1229.
33. Shaikh MTM, Gore A, Salunkhe KS, Chaudhari SR. Formulation Development & Evaluation of Fast Dissolving Oral Film of Amlodipine Besilate by Solvent Casting Technique. Int. J. Pharm. Biol. Sci.; 2013; 2: 534-44.
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