FACTORIAL DESIGN, OPTIMIZATION OF SWEETSOP STARCH AS A NEW NATURAL SUPERDISINTEGRANT IN THE FORMULATION OF CARVEDILOL FAST DISSOLVING TABLETS FOR BIOAVAILABILITY ENHANCEMENT

RAMA CHAKRADHAR DEVANI; SANTOSH KUMAR RADA

doi:10.22159/ijap.2025v17i3.53266

Authors

RAMA CHAKRADHAR DEVANI Department of Pharmaceutics, GITAM School of Pharmacy, GITAM (Deemed to be University), Rushikonda, Visakhapatnam-530045, Andhra Pradesh, India
SANTOSH KUMAR RADA Department of Pharmaceutics, GITAM School of Pharmacy, GITAM (Deemed to be University), Rushikonda, Visakhapatnam-530045, Andhra Pradesh, India

DOI:

https://doi.org/10.22159/ijap.2025v17i3.53266

Keywords:

Superdisintegrant, Sweetsop starch, In vitro dissolution, Bioavailability

Abstract

Objective: Carvedilol is a BCS class-II nonselective cardiac beta blocker with low bioavailability (35%) due to its poor solubility. To enhance the solubility and bioavailability, it can be formulated in Fast Dissolving Tablets (FDTs) employing a new natural superdisintegrant, Sweetsop starch, through factorial design.

Methods: Sweet Sop Starch (SSS) was extracted from the pulp of Annona squamosal L. The micromeritics characteristics of SSS were assessed, and the resulting product was utilized as a new superdisintegrant in the direct compression method of formulating Carvedilol (CRV) FDTs. The SSS was evaluated employing Fourier-transform infrared spectroscopy (FTIR), powdered x-ray diffraction, differential scanning calorimetry, and scanning electron microscopy. SSS, Potato starch (PS), and Sodium Starch Glycolate (SSG) were employed as superdisintegrants, and factorial design was used to investigate their disintegration property, Wetting Time (WT), and in vitro dissolution. The hardness, friability, homogeneity of Drug Content (DC), Water Absorption Ratio (R), in vivo pharmacokinetics, and stability parameters of formulated carvedilol FDTs were assessed.

Results: Micromeritic characteristics revealed that the produced SSS was fine, free-flowing, and crystalline. FTIR and DSC investigations indicated that there were no drug-excipient interactions. From the prepared formulations (F1 to F8), the one with a 5% SSS containing formulation CF2, demonstrated 98.44±1% drug release within ten minutes with 45±0.11 sec WT and had 32±01 sec DT. The optimized formula attained peak plasma concentration extremely quickly and showed 176.11 % relative bioavailability.

Conclusion: The formula containing 5% SSS showed good mechanical and physical characteristics, increased drug dissolution, and promoted quick disintegration with enhanced relative bioavailability in the management of hypertension and patient acceptance.

References

Sahithi M, Santosh Kumar R. Optimization of statistically designed aceclofenac fast dissolving tablets employing starch glutamate as a novel superdisintegrant. Int J Appl Pharm. 2020;12(1):77-88. doi: 10.22159/ijap.2020v12i1.34987.

Ashish P, Harsoliya MS, Pathan JK, Shruti S. A review: formulation of mouth dissolving tablet. Int J Pharm Clin Sci. 2011;1(1):1-8.

Raj, Behin Sundara, IS R, Punitha, Suraj Dube. Formulation and characterization of fast disintegrating tablets of amlodipine using super disintegrants. J App Pharm Sci. 2012;2(8):118-23. doi: 10.7324/JAPS.2012.2819.

Masih A, Kumar A, Singh S, Tiwari AK. Fast dissolving tablets: a review. Int J Curr Pharm Sci. 2017;9(2):8. doi: 10.22159/ijcpr.2017v9i2.17382.

Kumari N, Sharma R. An immediate release tablet of carvedilol with natural super disintegrants fenugreek seed mucilage and synthetic super disintegrants. Asian J Pharm Technol. 2020;10(3):156-64. doi: 10.5958/2231-5713.2020.00027.6.

Prakash Rao AH, Rada SK, Kandukuri S. Optimization of starch crotonate as a novel superdisintegrant in the formulation of fast dissolving tablets through 2³ factorial design. Int J App Pharm. 2021;7:247-56. doi: 10.22159/ijap.2021v13i4.41335.

Pinho LA, Temer AC, Ribeiro C, Sa-Barreto LL, Cunha Filho MS. The popularization of orodispersible tablets in the pharmaceutical market. Infarma. 2018;30(2):77-84. doi: 10.14450/2318-9312.v30.e2.a2018.pp77-84.

Aboud HM, El Komy MH, Ali AA, El Menshawe SF, Abd Elbary A. Development optimization and evaluation of carvedilol loaded solid lipid nanoparticles for intranasal drug delivery. AAPS Pharm Sci Tech. 2016;17(6):1353-65. doi: 10.1208/s12249-015-0440-8, PMID 26743643.

Lionberger RA, Lee SL, Lee L, Raw A, YU LX. Quality by design: concepts for ANDAs. AAPS J. 2008;10(2):268-76. doi: 10.1208/s12248-008-9026-7, PMID 18465252.

Borse LB, Bendale AR, Borse SL, Naphade VD, Jadhav AG. Formulation and evaluation of mouth dissolving tablet rivaroxaban and its validation. Biosci Biotechnol Res Asia. 2022;19(4):943-54. doi: 10.13005/bbra/3043.

DE Los Santos Santos MA, Balois Morales R, Bello Lara JE, Leon Fernandez AE, Jimenez Zurita JO, Bautista Rosales PU. Phytochemical compounds in soursop fruit starches (Annona muricata L.). Rev Bio Cienc. 2023;10. https://doi.org/10.15741/revbio.10.e1502.

Swarnalatha N, Maravajhala V. Formulation in vitro and in vivo evaluation of taste masked oral disintegrating tablets of fexofenadine hydrochloride using semisynthetic and natural superdisintegrants. Int J App Pharm. 2021;13(5):99-108. doi: 10.22159/ijap.2021v13i5.41558.

Singh R, Saxena S, Jain S. Formulation and evaluation of mouth dissolving tablet containing non-steroidal anti-inflammatory drug. Res J Pharm Technol. 2021;14(1):432-6. doi: 10.5958/0974-360X.2021.00078.0.

Kumar I, Chaudhary D, Thakur B, Pandit V. Formulation and evaluation of piroxicam fast dissolving tablets using direct compression and sublimation method. J Drug Delivery Ther. 2020;10(3-s):17-25. doi: 10.22270/jddt.v10i3-s.4063.

Kumari PV, Rao YS. Formulation and evaluation of orodispersible tablets of donepezil hydrochloride. Int J Curr Pharm Sci. 2020;12(4):45-51. doi: 10.22159/ijcpr.2020v12i4.39049.

Gugulothu D, Choudhary SK. Design and in vitro evaluation of floating drug delivery system of glipizide using a combination of natural mucilages and synthetic polymers. Int J Pharm Pharm Sci. 2021;13(7):40-8. doi: 10.22159/ijpps.2021v13i7.41644.

Nirmala D, Vidyavathi M. Preparation and evaluation of fast dissolving tablets of pitavastatin by 3² full factorial design. Int J Appl Pharm. 2020;12(1):108-14. doi: 10.22159/ijap.2020v12i1.35678.

Anusha K, Rada SK. Oral disintegrating tablets: best approach for faster therapeutic action of poorly soluble drugs. Egypt Pharm J. 2021;20(2):105-14. doi: 10.4103/epj.epj_63_20.

Anusha K, Santosh KR. Optimization of starch hyaluronate as a new super disintegrant in the formulation of fast dissolving tablets of nisoldipine. Eur Chem Bull. 2023;12(3):1606-32.

Nagar P, Singh K, Chauhan I, Verma M, Yasir M, Khan A. Orally disintegrating tablets: formulation preparation techniques and evaluation. J Appl Pharm Sci. 2011;4(1):35-45.

Aboud HM, El Komy MH, Ali AA, El Menshawe SF, Abd Elbary A. Development optimization and evaluation of carvedilol loaded solid lipid nanoparticles for intranasal drug delivery. AAPS PharmSciTech. 2016;17(6):1353-65. doi: 10.1208/s12249-015-0440-8, PMID 26743643.

Mazzo DJ. The ICH stability guideline. In: Mazzo DJ, editor. International stability testing. CRC Press; 2020. p. 1-13. doi: 10.1201/9781003076087-1.

Eisa AM, El Megrab NA, El Nahas HM. Formulation and evaluation of fast dissolving tablets of haloperidol solid dispersion. Saudi Pharm J. 2022;30(11):1589-602. doi: 10.1016/j.jsps.2022.09.002, PMID 36465849.

Jaya S, Amala V. Formulation and in vitro evaluation of oral disintegrating tablets of amlodipine besylate. Int J App Pharm. 2019;11(1):49. doi: 10.22159/ijap.2019v11i1.28457.

Dhahir RK, Al Kotaji M. Formulation of orally disintegrating tablets of cinnarizine by using the direct compression method. Int J Appl Pharm. 2019;11(1):117-23. doi: 10.22159/ijap.2019v11i1.29599.

Sharma V, Arora V. Comparison of various natural superdisintegrants in the formulation of fast dissolving carvedilol tablet. Int J Pharm Sci Res. 2012;3(10):3947. doi: 10.13040/IJPSR.0975-8232.3(10).3947-54.

Parfati N, Rani KC, Charles N, Geovany V. Preparation and evaluation of atenolol-β-cyclodextrin orally disintegrating tablets using co-process crospovidone sodium starch glycolate. Int J App Pharm. 2018;10(5):190. doi: 10.22159/ijap.2018v10i5.27982.

Sahoo CK, Mohanty D, Bhaskar J, Ramana DV. Formulation and evaluation of fast dissolving tablets of carvedilol using sodium starch glycolate. Int J Pharm Sci Rev Res. 2018;51(1):35-40.

Kusuma A, Santosh Kumar R. Optimization of fast dissolving tablets of carvedilol using 2³ factorial design. Int J App Pharm. 2024;16(1):98-107. doi: 10.22159/ijap.2024v16i1.49535.