International Journal of Pharma and Bio Sciences
    ISSN 0975-6299

Int J Pharm Bio Sci Volume 15 Issue 2, April-June, Pages:14-30

Formulation and In-Vitro Evaluation of Carvedilol Buccal Films Using HPMC E15 and Sago Starch as Polymer

Krishnaveni Manubolu , Mohammad Amisha Sulthana and K. Harinadha Baba

The study aimed to formulate and evaluate carvedilol-loaded buccal films using Sago starch and HPMC E15 as polymers. Carvedilol (Dose-3.125-25 mg) has α1-, β1- and β2-adrenergic blocker activity with other activities like antioxidant, calcium antagonist blocking, and smooth muscle proliferation action. Its oral bioavailability is 25-35% because of first-pass metabolism. Hence the main research objective is to formulate a buccal mucoadhesive dosage form for Carvedilol in the form of buccal Films by using two different semi-synthetic and natural polymers, Hydroxy Propyl Methyl Cellulose HPMC E15 and Sago Starch, to overcome the hepatic metabolism, reduce dosing frequency, low bioavailability, and to give controlled release of a drug and to improve patients’ compliance. The FTIR method revealed no interaction between carvedilol or any other polymers. Carvedilol buccal films were prepared using HPMC E15 and Sago starch solvent casting. The films were evaluated for thickness uniformity, folding endurance, weight uniformity, and content uniformity, swelling index, mucoadhesive strength, surface pH, kinetic, in-vitro, and Ex-vivo permeation studies. The thickness and weight uniformity of the prepared buccal films were found to be in a satisfactory range, the films have good folding-endurance over 300 folds, and the surface pH of the films ranged from 6.4-7 neutral pH. The drug content of the films was found to be uniform. The swelling index of buccal films was higher in the HPMC E15 films than in sago starch films. All buccal films have more than 7 hours of in-vitro residence time. The permeation studies were performed using goat buccal mucosa in a modified Franz diffusion cell for carvedilol-loaded buccal films in phosphate buffer for 8 hours, showing 95.04% permeation. In-vitro release studies were performed for carvedilolloaded buccal films in a phosphate buffer (6.8 pH) solution. The optimized film (S3) exhibited drug release 98.96% in 8 hours. Data from in-vitro release and ex-vivo permeation studies of films were fitted into kinetic models (Higuchi, Korsmeyer-Peppas models) to explain release profiles. The optimized formulations showed zero-order release followed by first-order and diffusion mechanisms (Higuchi). Thus, the prepared formulation of the carvedilol-loaded buccal film of sago starch and HPMC E15 can provide a controlled release and overcome the fast-pass metabolism of the drug.

Keywords: Carvedilol, HPMC E15, Sago Starch, Buccal films, Buccal Drug Delivery, fast-pass metabolism.
Full HTML:
  1. S. K. Mishra, Monika, P. Bhardwaj R. Singh, Ajay Kumar Shukla. "Formulation, optimization, and evaluation of buccal films of Diclofenac Sodium." 4 July 2019. Advance Pharmaceutical Journal 2019; 4(4):103-107
  2. Madhavi BR, Murthy VSN, Rani AP, Dileep Kumar Gattu DK. “Buccal film drug delivery system- An innovative and emerging technology.” 2013. Journal of Molecular Pharmaceutics & Organic Process Research, 1(3): 1-6.
  3. Sudhakar Y, Ketousetuo K, Bandyopadhyay AK, et al. “Buccal bioadhesive drug delivery: a promising option for orally less efficient drugs.”  2006.  J Control Release 114:15–40.
  4. Farnoosh K, Antonijevic MD, Chowdhry BZ, et al. “Formulation development of a carrageenan-based delivery system for buccal drug delivery using ibuprofen as a model drug.”  2011.  J Biomater Nano Biotechnology 2:582–95.
  5. Concetta G, Ayensu II, John JT, et al. “Development and characterization of chitosan films impregnated with insulin loaded PEG-b-PLA nanoparticles (NPs): a potential approach for buccal delivery of macromolecules.” 2012. Int J Pharm 428:143–51.
  6. Chowdary KPR, Shrinivas L. “Mucoadhesive Drug Delivery System: A Review of Current Status. Indian Drug.”  2000; 37(9):400-405
  7. Rana P, Murthy RS. “Formulation and evaluation of mucoadhesive buccal films impregnated with carvedilol nanosuspension: a potential approach for delivering drugs with high first-pass metabolism.” Drug delivery. 2013 Jun 1;20(5):224-35.
  8. Choudhary A, Tiwari G, Pandey M, Kymonil KM, Saraf SA. “Formulation and characterization of carvedilol buccal mucoadhesive patches.” Int. J. Res. Pharm. Sci. 2010;1(4):396-401.
  9. British Pharmacopoeia, Ed 2005: 1745. 
  10. Martindale: The Complete Drug Reference. 34th Edition, Published by Pharmaceutical Press. New York. 2004: 881.
  11. Parmar Viram J, Lumbhani AN, Vijayalakshmi P. “F0rmulation Development and Evaluation of Buccal Films of Carvedilol”. 2010. IJPSR, Vol.1, Issue 8.
  12. Mandakini Devi H, Balange AK, Viji P. Structural, thermal and film forming properties of gelatin from pink perch surimi refiner discharge.
  13. Baby A, Shivakumar HN, Alayadan P. Formulation and Evaluation of Film Forming Solution of Diphenhydramine Hydrochloride for Transdermal Delivery. Indian Journal of Pharmaceutical Education and Research. 2022 Jan 1;56(1):43-9.
  14. Kumar A, Bali V, Kumar M, Pathak K. Comparative evaluation of porous versus nonporous mucoadhesive films as the buccal delivery system of glibenclamide. Aaps Pharmscitech. 2013 Dec; 14:1321-32. 
  15. Habib F, Abdel Azeem M, Fetih G, Safwat M. Mucoadhesive buccal patches of lornoxicam: I-development and in-vitro characterization. Bulletin of Pharmaceutical Sciences. Assiut. 2010 Jun 30;33(1):59-68.
  16. Mady OY, Abulmeaty MM, Donia AA, Al-Khureif AA, Al-Shoubki AA, Abudawood M, Abdel Moety DA. Formulation and bioavailability of novel mucoadhesive buccal films for candesartan cilexetil in rats. Membranes. 2021 Aug 26;11(9):659.
  17. Costa ID, Abranches RP, Garcia MT, Pierre MB. Chitosan-based mucoadhesive films containing 5-aminolevulinic acid for buccal cancer treatment. Journal of Photochemistry and Photobiology B: Biology. 2014 Nov 1;140:266-75.
  18. Ammanage A, Rodriques P, Kempwade A, Hiremath R. Formulation and evaluation of buccal films of piroxicam co-crystals. Future Journal of Pharmaceutical Sciences. 2020 Dec;6(1):1-1. 
  19. Rasool BK, Khan SA. In vitro evaluation of miconazole mucoadhesive buccal films. Int J Appl Pharm. 2010;2(4):23-6. 
  20. Takeuchi Y, Kawamoto M, Tahara K, Takeuchi H. Design of a new disintegration test system for evaluating orally disintegrating films. International Journal of Pharmaceutics. 2018 Dec 20;553(1-2):281-9.
  21. Singh S, Jain S, Muthu MS, Tiwari S, Tilak R. Preparation and evaluation of buccal bioadhesive films containing clotrimazole. AAPS PharmSciTech. 2008 Jun;9:660-7.
  22. Singh S, Dharmesh S, Suresh SD, Sunil BB. Development and In vivo Bioavailability Evaluation of Sumatriptan Succinate Buccal Tablets. International Journal of Pharmaceutical Sciences and Nanotechnology (IJPSN). 2014 May 31;7(2):2477-86.
  23. Madhavi BR, Murthy VS, Rani AP, Kumar GD. Buccal film drug delivery system-an innovative and emerging technology. J Mol Pharm Org Process Res. 2013;1(3):2-6. 
  24. Kumria R, Al-Dhubiab BE, Shah J, Nair AB. Formulation and evaluation of chitosan-based buccal bioadhesive films of zolmitriptan. Journal of Pharmaceutical Innovation. 2018 Jun;13:133-43.
  25. Hanif M, Zaman M, Chaurasiya V. Polymers used in the buccal film: a Review. Designed Monomers and Polymers. 2015 Feb 17;18(2):105-11.
  26. Choudhary A, Tiwari G, Pandey M, Kymonil KM, Saraf SA. Formulation and characterization of carvedilol buccal mucoadhesive patches. Int. J. Res. Pharm. Sci. 2010;1(4):396-401.
  27. Nair AB, Al-Dhubiab BE, Shah J, Jacob S, Saraiya V, Attimarad M, Sree Harsha N, Akrawi SH, Shehata TM. Mucoadhesive buccal film of almotriptan improved therapeutic delivery in the rabbit model. Saudi Pharmaceutical Journal. 2020 Feb 1;28(2):201-9. 
  28. Nair AB, Kumria R, Harsha S, Attimarad M, Al-Dhubiab BE, Alhaider IA. “In vitro techniques to evaluate buccal films. Journal of Controlled Release.” 2013 Feb 28;166(1):10-21.
  29. Salehi S, Boddohi S. “New formulation and approach for the mucoadhesive buccal film of rizatriptan benzoate.” Progress in biomaterials. 2017 Dec;6:175- 87.
  30. Jagtap VD. “Development and evaluation of buccal film of carvedilol phosphate.” Indexing and Abstracting. 2020.
  31. Dinte E, Muntean DM, Andrei V, Bo?ca BA, Dudescu CM, BarbuTudoran L, Borodi G, Andrei S, Gal AF, Rus V, Gherman LM. “In Vitro and In Vivo Characterisation of a Mucoadhesive Buccal Film Loaded with  Doxycycline Hyclate for Topical Application in Periodontitis.” Pharmaceutics. 2023 Feb 8;15(2):580.
  32. Okazaki, M. “The Structure and Characteristics of Sago Starch.” In: Ehara, H., Toyoda, Y., Johnson, D. (eds) Sago Palm. Springer, Singapore. 2018.
  33. Nair AB, Al-Dhubiab BE, Shah J, Jacob S, Saraiya V, Attimarad M, Sree Harsha N, Akrawi SH, Shehata TM. Mucoadhesive buccal film of almotriptan improved therapeutic delivery in the rabbit model. Saudi pharmaceutical journal. 2020 Feb 1;28(2):201-9.
  34. D. Pathak, S. Pahwa and S. Singh. Formulation And Evaluation Of Sago Starch Film Containing Levocetirizine Dihydrochloride. IJPSR. 2021 Feb 1; Vol. 12(2): 1082-1091. 
  35. Takeuchi Y, Ikeda N, Tahara K, Takeuchi H. Mechanical characteristics of orally disintegrating films: Comparison of folding endurance and tensile properties. International Journal of Pharmaceutics. 2020 ;589:119876.
  36. Nappinnai M, Chandanbala R, Balaijirajan R. Formulation and evaluation of nitrendipine buccal films. Indian journal of pharmaceutical sciences. 2008 ;70(5):631.
  37. Poeloengasih CD, Anggraeni FD. Exploring the characteristics of sago starch films for pharmaceutical application. Starch?Stärke. 2014 :(11-12):1103-8.
  38. Hendradi E, Riantiny AI, Hasiholan J, Miatmoko A. The Effect of Different Ratios of the Hydrophilic Polymers Sodium Alginate 20cP and Hydroxy Propyl Methyl Cellulose E15 on the Physicochemical Characteristics of Meloxicam Patch. InProceedings of International Conference on Applied Pharmaceutical Sciences (ICoAPS) 2018.
  39. Tiwari S, Rajabi-Siahboomi A. Modulation of drug release from hydrophilic matrices. Pharmaceutical Technology Europe. 2008 ;20(9).
  40. Hasnain MS, Siddique MU, Gadewar MM, Ansari MT, Ahsan MN, Nandi G, Nayak AK. Uses of tailor-made plant starches in drug delivery. InTailor-Made Polysaccharides in Drug Delivery 2023  (pp. 327-346). Academic Press.
  41. Salehi S, Boddohi S. New formulation and approach for mucoadhesive buccal film of rizatriptan benzoate. Progress in biomaterials. 2017 ;6:175-87.
  42. Chan SY, Goh CF, Lau JY, Tiew YC, Balakrishnan T. Rice starch thin films as a potential buccal delivery system: Effect of plasticiser and drug loading on drug release profile. International journal of pharmaceutics. 2019 ;562:203-11.
  43. Soe MT, Pongjanyakul T, Limpongsa E, Jaipakdee N. Modified glutinous rice starch-chitosan composite films for buccal delivery of hydrophilic drug. Carbohydrate polymers. 2020 Oct 1;245:116556.
  44. Brouillet F, Bataille B, Cartilier L. High-amylose sodium carboxymethyl starch matrices for oral, sustained drug-release: formulation aspects and in vitro drug-release evaluation. International journal of pharmaceutics. 2008 May 22;356(1-2):52-60.
  45. Tuovinen L, Peltonen S, Järvinen K. Drug release from starch-acetate films. Journal of Controlled Release. 2003  4;91(3):345-54.
  46. Karthik M, Sunil R. Formulation And Evalution Of Terbutaline Sulphate Buccal Patches By Using Hpmc K4m, Hpmc E15 Polymers. World Journal of Pharmaceutical Research. 2017 Nov 28;7(2):1075-113.
[Download PDF]
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy
Pharmaceutical Fields
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Pharmaceutics
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Novel drug delivery system
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Nanotechnology
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Pharmacology
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Pharmacognosy
© Copyright 2009-2015 IJPBS, India. All rights reserved. Specialized online journals by ubijournal. Website by Ubitech Solutions
         Home I Contact I Terms & Conditions