Orodispersible tablets of telmisartan through cyclodextrin-surfactant complexation: A quality by design approach

Year 2022, Volume: 26 Issue: 5, 1202 - 1213, 28.06.2025

Lakshmanarao Potti Prameela Rani Avula

Abstract

Telmisartan is a poorly water-soluble drug with dissolution limited bioavailability. In this work,
solubility and dissolution rate were aimed to improve through the development of cyclodextrin (CD)
complexes containing surfactant; followed by developing them into orodispersible tablets (ODTs). Quality
by design approach was adopted in the optimization of CD-surfactant complex as well as in the optimization
of ODTs. Type of cyclodextrins, the concentration of the cyclodextrins, and concentration of poloxamer 188
were taken as the factors in the preparation of inclusion complexes by solvent evaporation method.
Solubility was taken as the response variable. The optimized formulation of the complex was taken for ODTs
preparation. Concentration of povidone, concentration of super-disintegrant and type of super-disintegrant
were taken as the independent factors, and disintegration time (DT) and time for 90% dissolution (T90%)
were taken as the responses. The tablets were prepared by direct compression technique. The results of both
the responses were analyzed by response surface quadratic model for the influence of the factors on them.
All three factors were found to have significant influence on both the responses (at p < 0.05). Graphical
optimization was performed by desirability functions approach in order to have low DT and low T90%. The
optimized telmisartan CD-surfactant complex was found to have a solubility of 2.86 mg/mL. The optimized
ODTs were found to have 20.4 sec. DT and 7.3 min. T90%. These results indicated that enhancement of
solubility of telmisartan as well as dissolution of the ODTs was successfully improved through quality by
design approach.

Keywords

Quality by design , solubility enhancement , dissolution enhancement , inclusion complexes , optimization , telmisartan , orodispersible tablets

References

• [1] Bhowmik D, Bhanot R, Gautam D, Rai P, Kumar KP. Formulation and evaluation of telmisartan fast dissolving tablets by direct compression method. Res J Pharm Dosage Form Tech. 2017; 9(3): 131-139. [CrossRef]
• [2] Park J, Cho W, Cha KH, Ahn J, Han K, Hwang SJ. Solubilization of the poorly water-soluble drug, telmisartan, using supercritical anti-solvent (SAS) process. Int J Pharm. 2013 Jan 30;441(1-2):50-55. [CrossRef]
• [3] Diana R, Jafari M. Angiotensin II-receptor antagonists: An overview. Am J Health Syst Pharm. 200; 57(13): 1231- 1241. [CrossRef]
• [4] Shaikh FI, Patel MB, Surti NI, Patel VB. Preparation and characterization of lercanidipine hydrochloride inclusion complex with β-cyclodextrin and effect of complexation on solubility and dissolution. Res J Pharm Tech 2017; 10(4): 1041-1048. [CrossRef]
• [5] Patel B, Parikh RH, Swarnkar D. Enhancement of dissolution of telmisartan through use of solid dispersion techniquesurface solid dispersion. J Pharm Bioall Sci. 2012; 4: 64-68. [CrossRef]
• [6] Eswaraiah MC, Jaya S. Enhancement of dissolution rate of telmisartan by solid dispersion technique. Res J Pharm Tech. 2020; 13(5): 2217-2220. [CrossRef]
• [7] Borba PA, Pinotti M, Andrade GR, da Costa Jr NB, Junior LR, Fernandes D, de Campos CE, Stulzer HK. The effect of mechanical grinding on the formation, crystalline changes and dissolution behaviour of the inclusion complex of telmisartan and β-cyclodextrins. Carbohydr Polym. 2015 ;133: 373-383. [CrossRef]
• [8] Arora P, Singh J, Chadha R. Physicochemical characterization and evaluation of telmisartan: hydroxypropyl- βcyclodextrin: Tween 80 inclusion complex. Int J Pharm Pharm Sci. 2017; 9(9): 51-58.
• [9] Araújo LD, Lazzara G, Chiappisi L. Cyclodextrin/surfactant inclusion complexes: An integrated view of their thermodynamic and structural properties. Adv Colloid Interface Sci. 2021; 289: 102375. [CrossRef]
• [10] Valente AJ, Söderman O. The formation of host–guest complexes between surfactants and cyclodextrins. Adv Colloid Interface Sci. 2014 ;205: 156-176. [CrossRef]
• [11] Joshi R, Akram W, Garud N, Dubey A, Bhadkariya S. Development and optimization of orodispersible tablets using solid dispersion of telmisartan. J Drug Deliv Ther.. 2018; 8(6): 171-178. [CrossRef]
• [12] Londhe VY, Umalkar KB. Formulation development and evaluation of fast dissolving film of telmisartan. Indian J Pharm Sci. 2012; 74(2): 122-126.
• [13] Chatterjee A, Abdulla SkM, Nagarajan G, Shrivastava B. Design, development and in vivo pharmacokinetic of telmisartan loadedoral disintegration tablets. Int J Res Pharm Sci. 2020; 11(4): 8108-8118.
• [14] Ramos JJ, Diogo HP. Thermal behavior and molecular mobility in the glassy state of three anti-hypertensive pharmaceutical ingredients. RSC Adv. 2017; 7(18): 10831-10840. [CrossRef]
• [15] Kim JS. Study of flavonoid/hydroxypropyl-β-cyclodextrin inclusion complexes by UV-Vis, FT-IR, DSC, and X-Ray diffraction analysis. Prev Nutr Food Sci. 2020; 25(4): 449-456. [CrossRef]
• [16] Mbah CJ, Ozuo CO. Effect of surfactants on the solubility and intrinsic dissolution rate of sparfloxacin. Pharmazie. 2011; 66(3): 192-194. [CrossRef]
• [17] Maheriya PM. Cyclodextrin: a promising candidate in enhancing oral bioavailability of poorly water soluble drugs. MOJ Bioequiv Availab. 2017; 3(3): 60-63. [CrossRef]
• [18] Mahours GM, Shaaban DE, Shazly GA, Auda SH. The effect of binder concentration and dry mixing time on granules, tablet characteristics and content uniformity of low dose drug in high shear wet granulation. J Drug Deliv Sci Technol. 2017; 39: 192-199. [CrossRef]
• [19] Pabari RM, Ramtoola Z. Effect of a disintegration mechanism on wetting, water absorption, and disintegration time of orodispersible tablets. J Young Pharm. 2012; 4(3): 157-163.
• [20] Islam A, Haider SS, Reza MS. Formulation and evaluation of orodispersible tablet of domperidone. Dhaka Univ J Pharm Sci. 2011; 10(2): 117-122. [CrossRef]
• [21] Debnath S, Gayathri VG, Swetha D, Babu MN. Evaluation of disintegration efficacy of starch citrate in tablet formulations. Asian J Pharm Res. 2020; 10(2): 73-80. [CrossRef]
• [22] Edge S, Miller RW. Sodium starch glycolate. In: Row RC, Sheskey PJ, Owen SC (Eds). Handbook of Pharmaceutical Excipients. Pharmaceutical Press, London, 2005, pp. 701-704.
• [23] Zhao N, Augsburger LL. The influence of swelling capacity of superdisintegrants in different pH media on the dissolution of hydrochlorothiazide from directly compressed tablets. AAPS Pharmscitech. 2005; 6(1): E120-126. [CrossRef]
• [24] USFDA, United States Food Drug Administration. https://www.fda.gov/regulatory-information/search-fdaguidance- documents/q8r2-pharmaceutical-development(accessed on January 2, 2022).
• [25] Pitt KG, Heasley MG. Determination of the tensile strength of elongated tablets. Powder Technol. 2013; 238: 169- 175. [CrossRef]
• [26] Malik K, Arora G, Singh I, Arora S. Lallemantia reylenne seeds as superdisintegrant: Formulation and evaluation of nimesulide orodispersible tablets. Int J Pharm Investig. 2011; 1(3): 192-198. [CrossRef]
• [27] Gupta B, Kumar S. Fast dissolving tablets of fexofenadine hydrochloride by melt technology: Formulation and characterization. Int J Pharm Sci Res. 2018; 9(3): 1226-30. [CrossRef]