DESIGN AND STATISTICAL OPTIMIZATION OF MUSKMELON PECTIN-BASED TELMISARTAN ORAL FAST DISSOLVING FILMS THROUGH QUALITY BY DESIGN

THAKUR REKHABAI; SANTOSH KUMAR

doi:10.22159/ijap.2025v17i6.54850

Authors

THAKUR REKHABAI Department of Pharmaceutics, GITAM School of Pharmacy, GITAM (Deemed to be University), Rushikonda, Visakhapatnam-530045, Andhra Pradesh, India https://orcid.org/0009-0009-3474-7480
SANTOSH KUMAR Department of Pharmaceutics, GITAM School of Pharmacy, GITAM (Deemed to be University), Rushikonda, Visakhapatnam-530045, Andhra Pradesh, India https://orcid.org/0000-0002-5541-9402

DOI:

https://doi.org/10.22159/ijap.2025v17i6.54850

Keywords:

Telmisartan, Oral fast dissolving films, Quality by design, Dissolution efficiency, solvent evaporation, Factorial designs

Abstract

Objective: This study aimed to design and statistically optimize oral fast-dissolving films containing telmisartan based on muskmelon pectin using a quality-by-design approach.

Methods: Cucumis melo pectin was extracted by acid hydrolysis. The physicochemical properties of muskmelon pectin were evaluated using FTIR, NMR, DSC, and SEM. The fast-dissolving films were made by solvent casting, and they were optimized using a 2³-factorial design. A two-way factorial design was used because it effectively assesses the impact of three film-forming polymers, namely muskmelon pectin, apple pectin, and citrus pectin, at two concentrations (0 mg and 350 mg), on important formulation responses such as percentage drug dissolution and dissolution efficiency within 10 min. With a few experimental runs, this strategy enables the investigation of both the independent and combined effects of factors. The Critical Quality Attributes (CQA) of each of the eight formulations were analyzed, including dissolution efficiency (DE%), disintegration time (DT), tensile strength (TS), thickness, and the percentage of drug dissolved in 10 min (PD%). The optimized formulation was evaluated for in vivo bioavailability in Wistar rats. The accelerated stability tests were performed according to ICH guidelines.

Results: The extracted muskmelon pectin was found to be amorphous and water-soluble, with a high degree of esterification, and exhibited satisfactory swelling index, viscosity, and pH values. Instrumental analyses using FT-IR, NMR, SEM, XRD, and DSC confirmed the material as pectin. The optimized formulation (F2) demonstrated favorable critical quality attributes, including drug dissolution efficiency at 10 min (DE₁₀min), tensile strength (TS), and percentage drug dissolved at 10 min (PD₁₀min), with drug release reaching approximately 95.61%. In vivo pharmacokinetic studies showed that TMF2 had significantly higher maximum plasma concentration (Cmax) and area under the curve (AUC), and relative bioavailability of 175.85%, showing a 75.85% enhancement over pure telmisartan, indicating the developed formulation significantly boosts drug absorption and may offer superior therapeutic effectiveness. Additionally, stability studies over six months revealed no significant changes in drug content, mechanical strength, or dissolution profiles, confirming the formulation’s stability and suitability for therapeutic use.

Conclusion: Telmisartan OFDFs were successfully designed and optimized using muskmelon pectin as a new film-forming agent through 2³ factorial designs, which exhibited 95.61% of the drug dissolution in 10 min and dissolution efficiency in 10 min alone, showing its better and efficient drug delivery.

References

1. Muralidhar S, Ramya K, T.V. Narayana, Sumaltha G, Rani N, Jayasree Prasanna R, Sri Nandini S.Oral Dissolving FIJAPilms: A Review. International Journal of Research and Review. 2023;10(9):450–465. https://doi.org/10.52403/ijrr.20230946

2. Saxena A, Singh T. Oral Dissolving Films: A Comprehensive Review on Recent Perspectives and Current Approach to Effective Drug Delivery. J Drug Deliv Ther. 2022 Mar 15;12(2):139–47. https://doi.org/10.22270/jddt.v12i2.5244

3. Gosse P. A review of telmisartan in the treatment of hypertension: blood pressure control in the early morning hours. Vasc Health Risk Manag. 2006;2(3):195–201. https://doi.org/10.2147/vhrm.2006.2.3.195

4. Chandel V, Biswas D, Roy S, Vaidya D, Verma A, Gupta A. Current Advancements in Pectin: Extraction, Properties and Multifunctional Applications. Foods. 2022 Sep 2;11(17):2683. https://doi.org/10.3390/foods11172683

5. Pardeshi C, Shevalkar G, Bari D, Singhai V, Kapadia R, Das U. Introduction to Quality by Design. In: Introduction to Quality by Design. 2024. https://doi.org/10.1007/978-981-99-8034-5_1

6. Liew SQ, Chin NL, Yusof YA. Extraction and Characterization of Pectin from Passion Fruit Peels. Agric Agric Sci Procedia.2014;2:231–6. https://doi.org/10.1016/j.aaspro.2014.11.033

7. Wang X, Chen Q, Lü X. Pectin extracted from apple pomace and citrus peel by subcritical water. Food Hydrocoll.2014;38:129–37. https://doi.org/10.1016/j.foodhyd.2013.12.003

8. Vakilian K, Nateghi L, Javadi A, et al. Extraction and Characterization of Pectins from Ripe Grape Pomace Using Both Ultrasound Assisted and Conventional Techniques. Food Anal Methods.2024;18:305–23. https://doi.org/10.1007/s12161-024-02710-w

9. Drishya CM, Wani KM. Exploring muskmelon peel as a novel source of pectin: Extraction methods and applications. Food Hum.2024;3:100331. https://doi.org/10.1016/j.foohum.2024.100331

10. Kumar A, Chauhan G. Extraction and characterization of pectin from apple pomace and its evaluation as lipase (steapsin) inhibitor. CarbohydrPolym.2010;82:454–9. https://doi.org/10.1016/j.carbpol.2010.05.001

11. Hossain A, Rana MM, Billah MT, Haque M. Optimizing Pectin Yield From Burmese Grape (Baccaurearamiflora) Peels Using Box–Behnken Design and Quality Evaluation. Int J Food Sci. 2024. https://doi.org/10.1155/2024/8064657

12. Patra PA, Basak U. Physicochemical Characterization of Pectin Extracted from Six Wild Edible Fruits in Odisha, India. Curr Res Nutr Food Sci J. 2020;8(2):402–9. https://doi.org/10.12944/CRNFSJ.8.2.05

13. Qin C, Yang G, Wu S, Zhang H, Zhu C. Synthesis, physicochemical characterization, antibacterial activity, and biocompatibility of quaternized hawthorn pectin. Int J Biol Macromol.2022;213:1047–56. https://doi.org/10.1016/j.ijbiomac.2022.06.028

14. Madhuvanthi S, Selvapriya K, Nirmala R, Agalya A, Jeya N. Extraction and characterization of pectin derived from underutilized papaya seeds as a value-added product. J Appl Nat Sci. 2022;14(1):127–32. https://doi.org/10.31018/jans.v14i1.3269

15. Shivamathi CS, Muthu GM, Raja VK, Soosai M, Maran J, Rajaram SK, Varalakshmi P. Optimization of Ultrasound Assisted Extraction of Pectin from Custard Apple Peel: Potential and New Source. CarbohydrPolym.2019;225:115240. https://doi.org/10.1016/j.carbpol.2019.115240

16. Zhou X, Liu L, Li J, Wang L, Song X. Extraction and Characterization of Pectin from Jerusalem Artichoke Residue and Its Application in Blueberry Preservation. Coatings. 2022;12(3):385. https://doi.org/10.3390/coatings12030385

17. Yang N, Wang D, Geng Y, Man J, Gao Y, Hang Y, Zheng H, Zhang M. Structure, physicochemical characterisation and properties of pectic polysaccharide from Premmapuberulapamp. Food Hydrocoll.2022;128:107550. https://doi.org/10.1016/j.foodhyd.2022.107550

18. Raihan R, Wafa A, Zhakfar AM, Sudhakar CK. Oral Disintegrating Films: A Review. J Nat Sci Rev. 2024;2(2):60–74. https://doi.org/10.62810/jnsr.v2i2.42

19. Devi MG, R SK. Design, Optimization and Evaluation of Ranolazine Fast-Dissolving Films Employing Mango Kernel Starch as a New Natural Superdisintegrant. Int J Appl Pharm. 2024;16(6):271–81. https://doi.org/10.22159/ijap.2024v16i6.51506

20. Hiremath HSP, Sansthanmath AM, Manjunath MKP, Choudhary S, Kole PS, Koshti GS, Shetiya AA, Mahesh MM. Formulation and Optimization of Fast Dissolving Buccal Films of Hydralazine HCl Using Design Expert Software. Int J Pharm Investig. 2024;15(1):265–76. https://doi.org/10.5530/ijpi.20251728

21. Kusuma A, Santosh R. Optimization of Fast-Dissolving Tablets of Carvedilol Using 2³ Factorial Design. Int J Appl Pharm. 2024;16(1):98–107. https://doi.org/10.22159/ijap.2024v16i1.49535

22. Pandey G, Kumar R, Sharma R, Singh Y, Teotia U. Development and Optimization of Oral Fast Dissolving Film of Salbutamol Sulphate by Design of Experiment. Am J PharmTech Res. 2013;3(2).

23. Farghaly DA, Afifi SA, Aboelwafa AA, et al. Oral Dissolving Film of Rivastigmine: Optimization Using Factorial Design. J Pharm Innov.2023;18:1892–907. https://doi.org/10.1007/s12247-023-09743-4

24. Bala R, Sharma S. Formulation optimization and evaluation of fast dissolving film of aprepitant by using design of experiment. Bull Fac Pharm Cairo Univ. 2018;56(2):159–68. https://doi.org/10.1016/j.bfopcu.2018.04.002

25. Daud A, Peepliwal A, Bonde M, Sapkal N, Gaikwad N, Gunawardena CB. Design and development of Nicotiana tabacum film using factorial design. Int J Pharm Pharm Sci. 2016;8(8):115–23.

26. Choudhary S, Harish KH, Sansthanmath AM, Mahesh M, Sagare RD, Dasankoppa FS, Swamy AHV. Design and Statistical Optimization of Fast-Dissolving Buccal Films of Doxylamine Succinate for Allergy Treatment. Int J Pharm Investig. 2024;14(4):1242–52. https://doi.org/10.5530/ijpi.14.4.137.

27. Husain M, Agnihotri VV, Goyal SN, Agrawal YO. Development, optimization and characterization of hydrocolloid based mouth dissolving film of telmisartan for the treatment of hypertension. Food Hydrocoll Health. 2022;2(100064):100064. https://doi.org/10.1016/j.fhfh.2022.100064

28. Londhe VY, Umalkar KB. Formulation development and evaluation of fast dissolving film of telmisartan. Indian J Pharm Sci. 2012;74(2):122–6. https://doi.org/10.4103/0250-474X.10384.

29. Pokhariya P, Ganarajan G, Preeti K. Formulation and evaluation of mouth dissolving tablet of telmisartan using natural superdisintegrants. Indo Am J Pharm Sci. 2016;3(7):271-281.