DISSOLUTION ENHANCEMENT AND FORMULATION OF FILM COATED TABLETS OF LORNOXICAM BY PHASE TRANSITION METHOD: IN VITRO AND IN VIVO EVALUATION
Objective: This study aimed to enhance the oral solubility and dissolution of poorly soluble lornoxicam by anti-solvent precipitation, and the manufacture of oral tablets by the phase transition method.
Methods: The solvent was mixture of polyethylene glycol 400 and absolute ethanol. Three stabilizers Inutec SP1, Pluronic F127, Sucrose ester S1670 at two concentrations and two matrix formers Mannitol, and Avicel PH102 were used to obtain 12 formulae. The formulae were characterized regarding their infrared spectroscopy (IR), differential scanning calorimetry (DSC), particle size (PS) measurement, drug content and dissolution. Further characterizations were done for the optimum formula by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Four tablet formulae were manufactured by phase transition method. The optimum tablets (T3) were evaluated through hardness, drug content, disintegration, dissolution, IR, and stability studies. Finally, (T3) was compared to conventional tablets in New Zealand rabbits using crossover design.
Results: The dissolution rate for the prepared formulae was enhanced, from 3.44 to 5.96 folds. Statistical significance was obtained using one and two way ANOVA among formulae. The optimum tablet formula (T3) had hardness 5.637±1.57 kg, drug content 90.424±1.19%, disintegration time 341.5±9.62 s and the drug dissolved 72.107±0.0025%. Stability, after one month storage of the selected tablets at (25 °c/60% relative humidity), was satisfactory. The absorption extent of lornoxicam from (T3) compared to the conventional tablets was higher.
Conclusion: Taken together, the obtained results confirmed successfully the potential of the promising formula (T3), over the conventional tablets of lornoxicam.
2. EL-Menshawe SF, Eissa E, Ali AA, Abderhman AA. Enhancement of lornoxicam solubility by inclusion complexation with cyclodextrin: preparation and characterization. Int J Pharm Pharm Sci 2017;9:132-8.
3. Nalini R, Ezhilramya J. A comparative study of efficacy and safety of lornoxicam and diclofenac as postoperative analgesics after mastoidectomy surgery. Int J Pharm Pharm Sci 2017;9:77-83.
4. Hitzenberger G, Radhofer Welte S, Takacs F, Rosenow D. Pharmacokinetics of lornoxicam in man. Postgrad Med J 1990;66 Suppl 4:S22-6.
5. Radhofer Welt S, Dittrich P. Determination of the novel non-steroidal anti-inflammatory drug lornoxicam and its main metabolite in plasma and synovial fluid. J Chromatogr B Biomed Appl 1998;707:151-9.
6. Kumar S, Bhargava D, Thakkar A, Arora S. Drug carrier systems for solubility enhancement of BCS class II drugs: a critical review. Crit Rev Ther Drug Carrier Syst 2013;30:217-56.
7. Shakeel F, Haq N, Alanazi F, Alsarra I. Solubility of anti-inflammatory drug lornoxicam in ten different green solvents at different temperatures. J Mol Liq 2015;209:280-3.
8. Salem HF, Kharshoum RM. Nanoprecipitation technique for preparation of sterically stabilized risperidone nano-suspension: in vitro and in vivo study. Int J Pharm Pharm Sci 2016;8:136-42.
9. Agiba AM, Eldin AB. Insights into formulation technologies and novel strategies for the design of orally disintegrating dosage forms: a comprehensive industrial review. Int J Pharm Pharm Sci 2019;11:8-20.
10. Lee JH, Chun IK. Effects of various vehicles and fatty acids on the skin permeation of lornoxicam. J Pharm Invest 2012;42:235-41.
11. Lin Y, Alexandridis P. Temperature-dependent adsorption of Pluronic F127 block copolymers on to carbon black particles dispersed in aqueous media. J Phys Chem B 2002;106:10834-44.
12. Srinarong P, Hämäläinen S, Visser MR, Hinrichs WL, Ketolainen J, Frijlink HW. Surface-active derivative of inulin (Inutec®SP1): Is a superior carrier for solid dispersions with a high drug load. J Pharma Sci 2011;100:2333-42.
13. Soultani S, Ognier S, Engasser JM, Ghoul M. Comparitive study of some surface active properties of fructose esters and commercial sucrose esters. Colloids Surfaces: A Physicochemical Engineering Aspects 2003;227:35-44.
14. Lonare AA, Patel SR. Antisolvent crystallization of poorly water soluble drugs. Int J Chem Eng Appl 2013;4:337-41.
15. Dumas JP, Gibout S, Zalewski L. Interpretation of calorimetry experiments to characterize phase change materials. Int J Therm Sci 2014;78:48-55.
16. Hasson KJ, Ghareeb MM. Evaluation of innovative co-processed additive for direct compression tablets using atorvastatin and diazepam as model drugs. Int J Pharm Pharm Sci 2016;8:201-7.
17. Gattani S, Moon R. Formulation and in vitro evaluation of tablet containing gliclazide nanocrystals for solubility and dissolution enhancement using soluplus. Int J Pharm Sci Res 2018;9:133-9.
18. Raghad AN, Hind EZ. Enhancement of candesartan cilexetil dissolution rate by using different methods. A J Pharm Clin Res 2015;8:320–6.
19. Yeap SP, Lim J, Ngang HP, Ooi BS, Ahmad AL. Role of particle-particle interaction towards effective interpretation of Z-Average and particle size distributions from dynamic light scattering (DLS) analysis. J Nanosci Nanotechnol 2018;18: 6957-64.
20. Brännstrom K, Islam T, Gharibyan AL, Lakovleva I, Nilsson L, Lee CC, et al. The properties of amyloid-? fibrils are determined by the nucleation pathway. J Mole Biol 2018;430:1940-9.
21. Shewale S, Shete AS, Doijad RC, Kadam SS, Patil VA, Yadav AV. Formulation and solid state characterization of nicotinamide-based co-crystals of fenofibrate. Ind J Pharm Sci 2015;77:328-34.
22. Kuno Y, Kojima M, Ando S, Nakagami H. Evaluation of rapidly disintegrating tablets manufactured by phase transition of sugar alcohols. J Controlled Release 2005;105:16-22.
23. Kuno Y, Kojima M, Nakagami H, Yonemochi E, Terada K. Effect of the type of lubricant on the characteristics of orally disintegrating tablets manufactured using the phase transition of sugar alcohol. Eur J Pharm Biopharm 2008;69:986-92.
24. Kuno Y, Kojima M, Ando S, Nakagami H. Effect of preparation method on properties of orally disintegrating tablets made by phase transition. Int J Pharm 2008;355:87-92.
25. British Pharmacopoeia. The stationary office under licence from the controller of Her Majesty’s stationary office for the department of health. London; 2007. p. A111, A112, A153.
26. Jassim ZE, Mohammed MF, Sadeq ZA. Formulation and evaluation of fast dissolving film of lornoxicam. Asian J Pharm Clin Res 2018;11:174-85.
27. Pharmacopoeia E. 6th ed. published by Council of Europe. Strasbourg, France; 2009. p. 1169-70.
28. Pharmacopoeia B. The stationary office under licence from the controller of Her Majesty’s stationary office. Norwich; 1998. p. 174.
29. Abraham S, Deveswaran R, Anbu J, Furtado S, Baharath S. Pharmacokinetic studies of a chronotherapeutic drug delivery system of lornoxicam by LC-MS/MS method. Int J Appl Pharm 2018;10:88-93.
30. Moutasim MY, ElMeshad AN, El-Nabarawi MA. A pharmaceutical study on lornoxicam fast disintegrating tablets: formulation and in vitro and in vivo evaluation. Drug Delivery Transl Res 2017;7:450-9.
31. Elsharawy AM, Shukr MH, Elshafeey AH. Optimization and in vivo evaluation of duloxetine hydrochloride buccoadhesive lyophilized tablets. J Drug Delivery Sci Tech 2019;52:282-91.
32. Matteucci ME, Hotez MA, Johnston KP, Williams III RO. Drug nanoparticles by antisolvent precipitation: Mixing energy versus surfactant stabilization. Langmuir 2006;22:8951-9.
33. Bilati U, Allémann E, Doelker E. Development of nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles. Eur J Pharm Sci 2005;24:67-75.
34. Cushing BL, Kolesnichenko VL, O'Connor CJ. Recent advances in the liquid-phase synthesis of inorganic nanoparticles. Chem Rev 2004;104:3893-946.
35. Tomassetti M, Catalnabi A, Rossi V, Vecchio S. Thermal analysis study of the interactions between acetaminophen and excipients in solid dosage forms and in some binary mixtures. J Pharm Biomed Anal 2005;37:949-55.
36. Merck Index. 13th ed. Merck and Co. Inc., Whitehouse Station, NJ, USA; 2001. p. 1000.
37. Botha SA, Lotter AP. Compatibility study between naproxen and tablet excipients using differential scanning calorimetry. Drug Dev Ind Pharm 1990;16:673-83.
38. Joshi BV, Patil VB, Pokharkar VB. Compatibility studies between carbamazepine and tablet excipients using thermal and non-thermal methods. Drug Dev Ind Pharm 2002;28:687-94.
39. Galindo Rodriguez S, Allémann SE, Fessi H, Doelker E. Physico-chemical parameters associated with nanoparticle formation in the salting out, emulsification-diffusion and nanoprecipitation methods. Pharm Res 2004;21:1428-39.
40. Hillstorm C, Jakobsson JG. Lornoxicam: pharmacology and usefulness to treat acute postoperative and musculoskeletal pain a narrative review. Expert Opin Pharmacother 2013;14:1679-94.
41. Dong Y, Ng WK, Hu J, Shen S, Tan RB. A continous and highly effective static mixing process for antisolvent precipitation of nanoparticles of poorly water-soluble drugs. Int J Pharm 2010;386:256-61.
42. Zimmermann A, Millqvist Fureby A, Elema MR, Hansen T, Müllertz A, Hovgaard L. Adsorption of pharmaceutical excipients onto microcrystals of siramesine hydrochloride: effects on physico-chemical properties. Eur J Pharm Biopharm 2009;71:109-16.
43. Xia D, Quan P, Piao H, Piao H, Sun S, Yin Y, et al. Preparation of stable nitrendipine nanosuspensions using the precipitation-ultrasonication method for enhancement of dissolution and oral bioavailability. Eur J Pharm Sci 2010;40:325-34.
44. Kocbek P, Baumgartner S, Kristl J. Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs. Int J Pharm 2006;312:179-86.
45. Masih A, Kumar A, Singh S, Tiwari AK. Fast dissolving tablets: a review. Int J Curr Pharm Res 2017;9:8-18.
46. Rudnic EM, Schwartz JD. Oral solid dosage forms. In: Alfonso RG. editor. Remington: The Science and Practice of Pharmacy. 20th ed. Philadelphia: Lippincot Williams and Wilkins Inc; 2000. p. 858-93.
47. Bhavani D, Rao NG. Formulation and evaluation of valsartan fast disintegrating tablets by vacuum drying technique. Asian J Pharm Clin Res 2016;9:73-9.
48. Dobrowolski A, Pieloth D, Wiggers H, Thommes M. Electrostatic precipitation of submicron particles in a molten carrier. Pharmaceutics 2019;11:1-7.
49. Juppo AM. Relationship between breaking force and pore structure of lactose, glucose and mannitol tablets. Int J Pharm 1996;127:95-102.
50. Mattsson S, Nystrom C. The use of mercury porosimetry in assessing the effect of different binders on the pore structure and bonding properties of tablets. Eur J Pharm Biopharm 2001;52:237-47.
51. Nystrom C, Karehill PG. Studies on direct compression of tablets: XVI. The use of surface area measurements for the evaluation of bonding surface area in compressed powders. Powder Technol 1986;47:201-9.
52. Nystrom C, Alderborn G, Duberg M, Karehill PG. Bonding surface area and bonding mechanism-two important factors for the understanding of powder compactability. Drug Dev Ind Pharm 1993;19:2143-96.
53. Agrawal A, Duhedia M, Deng W, Shepard K, Zong L, Povilaitis E, et al. Development of tablet formulation of amorphous solid dispersions prepared by hot melt extrusion using quality by design approach. AAPS PharmSciTech 2016;17:214-32.
54. Kathpalia H, Patil A. Formulation and evaluation of orally disintegrating films of levocetrizine dihydrochloride. Indian J Pharm Sci 2017;79:204-11.
55. Kianfar F, Antonijevic M, Chowdhry B, Boateng JS. Lyophilized wafers comprising carrageenan and pluronic acid for buccal drug delivery using model soluble and insoluble drugs. Colloids Surf B 2013;103:99-106.
56. Szymanska E, Winnicka K. Stability of chitosan-a challenge for pharmaceutical and biomedical applications. Mar Drugs 2015;13:1819-46.
57. Wong A, Xiang X, Ong P, Mitchell EQY, Syn N, Wee I, et al. A review on liquid chromatography-Tandem Mass spectrometry methods for rapid quantification of oncology drugs. Pharmaceutics 2018;10:1-20.
58. El-Mahmoudy A. Pharmacokinetics of lornoxicam in rabbits after single intravenous bolus and intramuscular administrations. Int J Pharmacol Toxicol 2016;4:66-73.
This work is licensed under a Creative Commons Attribution 4.0 International License.