Mucoadhesive Film Forming Spray for Buccal Drug Delivery: A Review


  • Reem Wael Shahadha Department of Pharmaceutics, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
  • Nidhal Khazaal Maraie Department of Pharmaceutics, College of Pharmacy, Al Farahidi University, Baghdad, Iraq



Film-Forming spray, Polymer, Buccal Drug Delivery System


Film-forming sprays provide a number of advantages over conventional topical treatments, including equal medication distribution and dosing, increased bioavailability (increase local drug concentration), and less irritability (Dosing frequency). Polymers and excipients that improve the characteristics of preparations and increase the stability of active substances are the building blocks of mucoadhesive film-forming sprays. Films made from diverse combinations of polymer and excipient exhibited a wide range of characteristics. This reveiw examines the many types of polymers and excipients, the different types of sprayers, the different evaluations, as well as the essential criteria that are involved in defining the sprayability and film properties. This comes to the conclusion that natural and synthetic polymers with viscoelastic properties can both be employed to optimize the administration of buccal drugs.


- Bogue MH. Orally dissolving film strips (ODFS): The final evolution of orally dissolving dosage forms. Drug Deliv Technol. 2009;9(2):24–9.

- K K Peh 1 CFW. Polymeric films as vehicle for buccal delivery: swelling, mechanical, and bioadhesive properties. J Pharm Pharm Sci. 1999;2(2):53–61.

- Singh S, Jain S, Muthu MS, Tiwari S, Tilak R. Preparation and Evaluation of Buccal Bioadhesive Films Containing Clotrimazole. AAPS PharmSciTech. 2008 Jun;9(2):660–7.

- DAWES LMCC and C. The Surface Area of the Adult Human Mouth and Thickness of the Salivary Film Covering the Teeth and Oral Mucosa. Res, J Dent. 1987;66(8):1300–2.

- Alopaeus JF, Hellfritzsch M, Gutowski T, Scherließ R, Almeida A, Sarmento B, et al. Mucoadhesive buccal films based on a graft co-polymer – A mucin-retentive hydrogel scaffold. Eur J Pharm Sci. 2020;142:105142.

- Caon T, Jin L, Simões CMO, Norton RS, Nicolazzo JA. Enhancing the buccal mucosal delivery of peptide and protein therapeutics. Pharm Res. 2015;32(1):1–21.

- Morales JO, Brayden DJ. Buccal delivery of small molecules and biologics: of mucoadhesive polymers, films, and nanoparticles. Curr Opin Pharmacol. 2017;36:22–8.

- Bagan J, Paderni C, Termine N, Campisi G, Lo Russo L, Compilato D, et al. Mucoadhesive polymers for oral transmucosal drug delivery: a review. Curr Pharm Des. 2012 Oct;18(34):5497–514.

- Chinna Reddy P, Chaitanya KSCC, Madhusudan Rao Y. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods. Daru. 2011;19(6):385–403.

- Pelin IM, Suflet DM. Mucoadhesive buccal drug delivery systems containing polysaccharides. Cellul Chem Technol. 2020;54(9–10):889–902.

- Płaczek M, Sznitowska M. [The mucoadhesion phenomena and importance in drug application]. Polim Med. 2009;39(2):49–64.

- Zhong Y, Zhuang C, Gu W, Zhao Y. Effect of molecular weight on the properties of chitosan films prepared using electrostatic spraying technique. Carbohydr Polym. 2019 May;212(February):197–205.

- Kathe K, Kathpalia H. Film forming systems for topical and transdermal drug delivery. Asian J Pharm Sci. 2017;12(6):487–97.

- Ranade S, Bajaj A, Londhe V, Babul N, Kao D. Fabrication of topical metered dose film forming sprays for pain management. Eur J Pharm Sci. 2017 Mar;100:132–41.

- Geh KJ, Stelzl A, Gröne A, Wagner L, Förster B, Winter G. Development of a sprayable hydrogel formulation for the skin application of therapeutic antibodies. Eur J Pharm Biopharm. 2019 Sep;142:123–32.

- Tan X, Feldman SR, Chang J, Balkrishnan R. Topical drug delivery systems in dermatology: a review of patient adherence issues. Expert Opin Drug Deliv. 2012 Oct;9(10):1263–71.

- Mahmood A. Haiss, Nidhal K. Maraie. Preparation and evaluation of oral capsules containing apigenin nanocrystals prepared by ultrasonication. Al Mustansiriyah J Pharm Sci. 2022;21(3):16–24.

- Ghosh TK, Pfister WR, editors. Drug Delivery to the Oral Cavity. CRC Press; 2005.

- Baio FHR, Antuniassi UR, Castilho BR, Teodoro PE, Silva EE da. Correction: Factors affecting aerial spray drift in the Brazilian Cerrado. PLoS One. 2019 Jun;14 (6):e0217957.

- Gaytan I, Nicolas B, Gouriou F, Leru JP, Mallarach J. Effect of working pressure, fluid temperature, nozzle type and nozzle orifice size, on spray characteristics using viscous feed additiveDL-2-hydroxy-4-(methylthio) -butanoic-acid. Powder Technol. 2018 Aug;336(2017):383–92.

- Amar Lulla C. and Malhotra M. TOPCAL SPRAY COMPOSITIONS. Long Island City, NY.USA. Novamber 2005. Vol. 8.

- Joseph Sandor. VARIABLE SPRAY NOZZLE FOR PRODUCT SPRAYER. USA: United States Patent (19); 5,941,462, 1999. p. 8.

- Nogueira Martins R, Moraes HMF e, Freitas MAM de, Lima A da C, Furtado Junior MR. Effect of nozzle type and pressure on spray droplet characteristics. Idesia (Arica). 2021;39(1):101–7.

- Lefebvre AH, Mcdonell VG. Atomization and Sprays, Second Edition. 2nd ed. CRC Press, Taylor and Francis. 2017. 300 p.

- Kumar R, Philip A. Modified Transdermal Technologies: Breaking the Barriers of Drug Permeation via the Skin. Trop J Pharm Res. 2007;6(1):633–44.

- Thosar MM. Intra oral sprays -An overview. Int J Pharm Life Sci. 2011;2(11):1235–46.

- Kovács G, Zelei T, Vokó Z. Comparison of efficacy and local tolerability of estradiol metered-dose transdermal spray to estradiol patch in a network meta-analysis. Climacteric. 2016 Oct;19(5):488–95.

- Umar AK, Butarbutar M, Sriwidodo S, Wathoni N. Film-Forming Sprays for Topical Drug Delivery. Drug Des Devel Ther. 2020 Jul;14:2909–25.

- Bajaj A, Malhotra G, Madan M, Amrutiya N, Bakshi A. A novel metered dose transdermal spray formulation for oxybutynin. Indian J Pharm Sci. 2008;70(6):733.

- Sulaiman HT, Jabir SA, Kadhem Al-kinani K. Investigating the effect of different grades and concentrations of ph-sensitive polymer on preparation and characterization of lidocaine hydrochloride as in situ gel buccal spray. Asian J Pharm Clin Res. 2018;11(11):401–7.

- Maraie NK, Almajidi YQ. Effect of different mucoadhesive polymers on release of ondansetron HCl from intranasal mucoadhesive in situ gel. Al Mustansiriyah J Pharm Sci. 2018;17(2):10.

- Sharma M, Rathore A, Sharma S, Sadhu V, Reddy KR, Kulkarni R V. Recent progress in mucoadhesive polymers for buccal drug delivery applications. Nanomaterials in Diagnostic Tools and Devices. INC; 2020. 213–240 p.

- Lu W, Luo H, Zhu Z, Wu Y, Luo J, Wang H. Preparation and the Biopharmaceutical Evaluation for the Metered Dose Transdermal Spray of Dexketoprofen. J Drug Deliv [Internet]. 2014 Feb 11;2014:1–12.

- Grip J, Engstad RE, Skjæveland I, Škalko-Basnet N, Holsæter AM. Sprayable Carbopol hydrogel with soluble beta-1,3/1,6-glucan as an active ingredient for wound healing - Development and in-vivo evaluation. Eur J Pharm Sci. 2017 Sep;107:24–31.

- Nicolazzo JA, Reed BL, Finnin BC. Assessment of the Effects of Sodium Dodecyl Sulfate on the Buccal Permeability of Caffeine and Estradiol. J Pharm Sci. 2004;93(2):431–40.

- Borrás-Blasco J, López A, Morant MJ, Díez-Sales O, Herráez-Domínguez M. Influence of sodium lauryl sulphate on the in vitro percutaneous absorption of compounds with different lipophilicity. Eur J Pharm Sci. 1997;5(1):15–22.

- Sukhbir K, Navneet K, Sharma AK, Kapil K. Development of modified transdermal spray formulation of psoralen extract. Der Pharm Lett. 2013;5(2):85–94.

- Hoogstraate AJ, Senel S, Cullander C, Verhoef J, Junginger HE, Boddé HE. Effects of bile salts on transport rates and routes of FITC-labelled compounds across porcine buccal epithelium in vitro. J Control Release. 1996;40(3):211–21.

- Deneer VHM, Drese GB, Roemelé PEH, Verhoef JC, Lie-A-Huen L, Kingma JH, et al. Buccal transport of flecainide and sotalol: Effect of a bile salt and ionization state. Int J Pharm. 2002;241(1):127–34.

- Sahni J, Raj S, Ahmad FJ, Khar RK. Design and in vitro characterization of buccoadhesive drug delivery system of insulin. Indian J Pharm Sci. 2008 Jan;70(1):61–5.

- Taylor P, Abu-huwaij R. Potential Mucoadhesive Dosage Form of Lidocaine Hydrochloride : II . In Vitro and In Vivo Evaluation. (August 2015).

- Manganaro AM, Wertz PW. The effects of permeabilizers on the in vitro penetration of propranolol through porcine buccal epithelium. Mil Med. 1996;161(11):669–72.

- Morishita M, Barichello JM, Takayama K, Chiba Y, Tokiwa S, Nagai T. Pluronic F-127 gels incorporating highly purified unsaturated fatty acids for buccal delivery of insulin. Int J Pharm. 2001 Jan;212(2):289–93.

- Abdullah Q. Khudhur, Nidhal K. Maraie, Ayad M.R. Raauf. Highlight on lipids and its use for covalent and non-covalent conjugations. Al Mustansiriyah J Pharm Sci. 2020;20(3):1–13.

- Meng R, Yin D, Drapaca CS. A variable order fractional constitutive model of the viscoelastic behavior of polymers. Int J Non Linear Mech. 2019 Jul;113:171–7.

- Nicolazzo JA, Reed BL, Finnin BC. Modification of buccal drug delivery following pretreatment with skin penetration enhancers. J Pharm Sci. 2004;93(8):2054–63.

- Howie NM, Trigkas TK, Cruchley AT, Wertz PW, Squier CA, Williams DM. Short-term exposure to alcohol increases the permeability of human oral mucosa. Oral Dis. 2001;7(6):349–54.

- Trottet L, Merly C, Mirza M, Hadgraft J, Davis A. Effect of finite doses of propylene glycol on enhancement of in vitro percutaneous permeation of loperamide hydrochloride. Int J Pharm. 2004 Apr;274(1–2):213–9.

- Leichtnam ML, Rolland H, Wüthrich P, Guy RH. Formulation and evaluation of a testosterone transdermal spray. J Pharm Sci. 2006 Aug;95(8):1693–702.

- Reid ML, Benaouda F, Khengar R, Jones SA, Brown MB. Topical corticosteroid delivery into human skin using hydrofluoroalkane metered dose aerosol sprays. Int J Pharm. 2013 Aug;452(1–2):157–65.

- Mahdi ZH, Maraie NK, Al-Juboori ZA. Application of liquisolid technology to enhance the dissolution of cefixime from its oral capsules. Int J Appl Pharm. 2018;10(5):214–9.

- Vervaet C, Byron PR. Drug–surfactant–propellant interactions in HFA-formulations. Int J Pharm. 1999 Sep;186(1):13–30.

- Puratchikody A, Prasanth V V., Mathew ST, Kumar AB. Buccal drug delivery: Past, present and future - A review. Int J Drug Deliv. 2011;1(2):171–84.

- Gohel MC, Nagori SA. Fabrication of Modified Transport Fluconazole Transdermal Spray Containing Ethyl Cellulose and Eudragit® RS100 as Film Formers. AAPS PharmSciTech. 2009 Jun;10 (2):684–91.

- Ghareeb MM, Mohammad HA. Study the effects of secondary polymers on the properties of buccoadhesive polyvinyl alcohol patches of 5-Flourouracil. Int J Pharm Pharm Sci. 2013;5 (SUPPL.4):484–8.

- Vávrová K, Lorencová K, Klimentová J, Novotný J, Holý A, Hrabálek A. Transdermal and dermal delivery of adefovir: Effects of pH and permeation enhancers. Eur J Pharm Biopharm. 2008 Jun;69(2):597–604.

- Salehi S, Boddohi S. New formulation and approach for mucoadhesive buccal film of rizatriptan benzoate. Prog Biomater. 2017;6(4):175–87.

- Patil BSST, Kulkarni U, Hariprasanna RC, Wadageri GV. Development and in-vitro evaluation of mucoadhesive buccal tablets of Tizanidine hydrochloride using natural polymer xanthan gum. Int J Pharm Sci Rev Res [Internet]. 2011;8(2):140–6.

- Liu X, Doub WH, Guo C. Assessment of the influence factors on nasal spray droplet velocity using phase-Doppler anemometry (PDA). AAPS PharmSciTech. 2011 Mar;12(1):337–43.

- Monton C, Settharaksa S, Suksaeree J, Chusut T. The preparation, characterization, and stability evaluation of a microemulsion-based oral spray containing clove oil for the treatment of oral candidiasis. J Drug Deliv Sci Technol. 2020;57:1–7.

- Mahadlek J, Myo Thurein S, Thammasut W, Phaechamud T. Clotrimazole-loaded fatty acid-based in situ forming film oral spray. Mater Today Proc [Internet]. 2022 Jan 1 [cited 2022 Jul 20];52(xxxx):2479–84.

- Paradkar M, Thakkar V, Soni T, Gandhi T, Gohel M. Formulation and evaluation of clotrimazole transdermal spray. Drug Dev Ind Pharm. 2015 Oct;41(10):1718–25.

- Gohel MC, Nagori SA. Fabrication of Modified Transport Fluconazole Transdermal Spray Containing Ethyl Cellulose and Eudragit® RS100 as Film Formers. AAPS PharmSciTech. 2009;10(2):684–91.

- Paradkar M, Thakkar V, Soni T, Gandhi T, Gohel M. Formulation and evaluation of clotrimazole transdermal spray. Drug Dev Ind Pharm [Internet]. 2015 Oct 3;41(10):1718–25.

- Lu W, Luo H, Wu Y, Zhu Z, Wang H. Preparation and characterization of a metered dose transdermal spray for testosterone. Acta Pharm Sin B. 2013 Dec;3(6):392–9.

- Bajaj A, Malhotra G, Madan M, Amrutiya N, Bakshi A. A novel metered dose transdermal spray formulation for oxybutynin. Indian J Pharm Sci [Internet]. 2008; 70(6):733.

- Radhakrishnan A, Kuppusamy G, Karri VVSR. Spray bandage strategy in topical drug delivery. J Drug Deliv Sci Technol. 2018 Feb;43:113–21.

- Edwards A, Qi S, Liu F, Brown MB, McAuley WJ. Rationalising polymer selection for supersaturated film forming systems produced by an aerosol spray for the transdermal delivery of methylphenidate. Eur J Pharm Biopharm. 2017 May; 114:164–74.

- Sabri LA, Sulayman HT, Ameen DW. Formulation of Tinidazole as an Oral Suspension Dosage Form. Al Mustansiriyah J Pharm Sci. 2013;13(1):82–93.