A NOVEL DRUG DELIVERY SYSTEM OF INDIGENOUS HERBS FOR SUBLINGUAL IMMUNOTHERAPY IN COPD
DOI:
https://doi.org/10.22159/ijpps.2025v17i3.53317Keywords:
Bilayer tablet, Sublingual, Butterbur, Bee’s pollen, SLIT, COPD, Ex-vivo, In vitro, PermeabilityAbstract
Objective: To develop and evaluate bilayer sublingual tablets containing Butterbur and Bee’s Pollen extracts for the management of Chronic Obstructive Pulmonary Disease (COPD). The aim was to achieve anti-inflammatory, anti-allergic, and immune-modulatory effects via a non-invasive delivery system, improving patient compliance and therapeutic outcomes.
Methods: Bilayer tablets were formulated using direct compression, with Bee’s Pollen serving as the immune-modulatory layer and Butterbur as the anti-inflammatory layer. The tablets were evaluated for pre- and post-compression parameters, including flow properties, hardness, friability, disintegration, and dissolution. Fourier Transform Infrared (FTIR) spectroscopy confirmed drug-excipient compatibility. In vitro drug release studies were conducted, and ex vivo permeation studies using goat buccal mucosa simulated sublingual absorption. Stability tests followed ICH guidelines to ensure physical and chemical consistency under accelerated conditions.
Results: The bilayer tablets exhibited rapid disintegration (<3 minutes) and high drug release (>90%) during dissolution studies. FTIR analysis confirmed the absence of significant drug-excipient interactions. Ex vivo permeation studies demonstrated efficient drug absorption, supporting systemic delivery. Stability tests revealed no significant changes in parameters over 30 days. The best formulations, F8 and F9, showed superior dissolution and permeation profiles, with cumulative drug release reaching 94.91% (Butterbur) and 93.3% (Bee’s Pollen).
Conclusion: Bilayer sublingual tablets combining Butterbur and Bee’s Pollen extracts present a promising therapeutic strategy for COPD. The dual action of these herbal extracts offers enhanced anti-inflammatory and immune-modulating effects, potentially improving patient outcomes and compliance. Further clinical trials are recommended to validate these findings and explore long-term therapeutic potential.
Downloads
References
Liu, J., Ran, Z., Wang, F., Xin, C., Xiong, B., & Song, Z. (2020). Role of pulmonary microorganisms in the development of chronic obstructive pulmonary disease. Critical Reviews in Microbiology, 47(1), 1–12. https://doi.org/10.1080/1040841X.2020.1830748.
Suberna Basnet, Yallasai Vijaya Durga, Sunny Kumar Yadav, Subhi Adhikari, Sijina Ks. Effects of Socioeconomic and Clinical Factors on Treatment Adherence in Patients with Chronic Obstructive Pulmonary Diseases Patient: Focus on Inhalation Therapy. Asian J Pharm Clin Res. 2024 Oct. 7; 17(10):138-42.
Singh D, Agusti A, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Criner GJ, Frith P, Halpin DMG, Han M, López Varela MV, Martinez F, Montes de Oca M, Papi A, Pavord ID, Roche N, Sin DD, Stockley R, Vestbo J, Wedzicha JA, Vogelmeier C. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J. 2019 May 18;53(5):1900164. doi: 10.1183/13993003.00164-2019. PMID: 30846476.
World Health Organization: WHO, World Health Organization: WHO. Chronic obstructive pulmonary disease (COPD). 2024. https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)
P, Sucharitha J L, Sindhu M J, Teja A C, B M. Study on Risk Factors, Clinical and Therapeutic Profile of Chronic Obstructive Pulmonary Disease Patients in Government General Hospital. Asian J Pharm Clin Res. 2021 Mar. 7; 14(3):60-5.
MacNee W. Pathogenesis of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2(4):258-66; discussion 290-1. doi: 10.1513/pats.200504-045SR. PMID: 16267346; PMCID: PMC2713323.
Negewo, N.A., Gibson, P.G. and McDonald, V.M. (2015), COPD and its comorbidities. Respirology, 20: 1160-1171. https://doi.org/10.1111/resp.12642.
Aswal P, Bhumbla U. Prevalence of Cardiovascular Comorbidities in Patients with Chronic Obstructive Pulmonary Disease In Suburban Areas of South-West India. Asian J Pharm Clin Res. 2022 May 7; 15(5):72-5.
Fatima D, Tiwari S, Gowardipe Ps, Sk S. Study of Lipid Profile and Atherogenic Index in Patients with Chronic Obstructive Pulmonary Disease. Asian J Pharm Clin Res. 2022 Dec. 7; 15(12):184-6.
Weiss A, Porter S, Rozenberg D, O'Connor E, Lee T, Balter M, Wentlandt K. Chronic Obstructive Pulmonary Disease: A Palliative Medicine Review of the Disease, Its Therapies, and Drug Interactions. J Pain Symptom Manage. 2020 Jul;60(1):135-150. doi: 10.1016/j.jpainsymman.2020.01.009. Epub 2020 Jan 29. PMID: 32004618.
Devi M K, S S, Lalsasidharan S, S S, Shaik M, Sandeep G, Lal Sasidharan S, Rajasekhar V, Shaik M, N D, Sandeep G, Rajasekhar V, N D. A Clinical Study on Safety and Efficacy of Formoterol and Tiotropium Combination Compared to Formoterol and Tiotropium with Roflumilast Combination in Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease Patients. Asian J Pharm Clin Res. 2018 Mar. 1; 11(3):184-6.
Nurhidayah M, Fadilah F, Arsianti A, Bahtiar A. Identification of FGFR Inhibitor as ST2 Receptor/Interleukin-1 Receptor-Like 1 Inhibitor in Chronic Obstructive Pulmonary Disease Due to Exposure to E-Cigarettes by Network Pharmacology and Molecular Docking Prediction. Int J App Pharm. 2022 Mar. 7; 14(2):256-6.
Ejiofor S, Turner AM. Pharmacotherapies for COPD. Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine. 2013;7. doi:10.4137/CCRPM.S7211.
Braghiroli, A., Braido, F., Piraino, A., Rogliani, P., Santus, P., & Scichilone, N. (2020). Day and Night Control of COPD and Role of Pharmacotherapy: A Review. International Journal of Chronic Obstructive Pulmonary Disease, 15, 1269–1285. https://doi.org/10.2147/COPD.S240033.
Chalela R, Gea J, Barreiro E. Immune phenotypes in lung cancer patients with COPD: potential implications for immunotherapy. J Thorac Dis. 2018 Jul;10(Suppl 18):S2186-S2189. doi: 10.21037/jtd.2018.06.143. PMID: 30123556; PMCID: PMC6072947.
Qi, Y., Yan, Y., Tang, D., Han, J., Zhu, X., Cui, M., … Fan, F. (2024). Inflammatory and Immune Mechanisms in COPD: Current Status and Therapeutic Prospects. Journal of Inflammation Research, 17, 6603–6618. https://doi.org/10.2147/JIR.S478568.
Cox LS, Larenas Linnemann D, Nolte H, Weldon D, Finegold I, Nelson HS. Sublingual immunotherapy: a comprehensive review. J Allergy Clin Immunol. 2006 May;117(5):1021-35. doi: 10.1016/j.jaci.2006.02.040. PMID: 16675328.
Baba SM, Rasool R, Gull A, Qureshi TA, Beigh AH, Qadri Q, Shah ZA. Effectiveness of Sublingual Immunotherapy in the Treatment of HDM-Induced Nasobronchial Allergies: A 3-Year Randomized Case-Control Study From Kashmir. Front Immunol. 2021 Oct 13;12:723814. doi: 10.3389/fimmu.2021.723814. PMID: 34721385; PMCID: PMC8548833.
Zeng Y, Xiao H, Gao S, Li J, Yang C, Zeng Q, Luo X, Luo R, Chen X, Liu W. Efficacy and immunological changes of sublingual immunotherapy in pediatric allergic rhinitis. World Allergy Organ J. 2023 Jul 23;16(7):100803. doi: 10.1016/j.waojou.2023.100803. PMID: 37520614; PMCID: PMC10382672.
Lawrence MG, Steinke JW, Borish L. Basic science for the clinician: Mechanisms of sublingual and subcutaneous immunotherapy. Ann Allergy Asthma Immunol. 2016 Aug;117(2):138-42. doi: 10.1016/j.anai.2016.06.027. PMID: 27499541; PMCID: PMC4978173.
Głobińska, Anna et al. Mechanisms of allergen-specific immunotherapy. Annals of Allergy, Asthma & Immunology, Volume 121, Issue 3, 306 – 31.
Arefin P, Habib Ms, Ahmed Nu, Rahim Ma, Ibrahim M, Bhattacharjee Sc, Chakraborty D, Das S, Karmakar D, Bhowmik D, Islam S, Arefin Ms. Allergic Rhinitis, and Importance of Fexofenadine HCL Sustained Release Microsphere as its Treatment Approach. Int J App Pharm. 2022 Jan. 7; 14(1):13-7.
Canonica GW, Cox L, Pawankar R, Baena-Cagnani CE, Blaiss M, Bonini S, Bousquet J, Calderón M, Compalati E, Durham SR, van Wijk RG, Larenas-Linnemann D, Nelson H, Passalacqua G, Pfaar O, Rosário N, Ryan D, Rosenwasser L, Schmid-Grendelmeier P, Senna G, Valovirta E, Van Bever H, Vichyanond P, Wahn U, Yusuf O. Sublingual immunotherapy: World Allergy Organization position paper 2013 update. World Allergy Organ J. 2014 Mar 28;7(1):6. doi: 10.1186/1939-4551-7-6. PMID: 24679069; PMCID: PMC3983904.
Kulalert P, Phinyo P, Lao-Araya M. Efficacy and safety of house dust mite sublingual immunotherapy tablets in allergic rhinitis: A systematic review and meta-analysis. World Allergy Organ J. 2022 Sep 7;15(9):100691. doi: 10.1016/j.waojou.2022.100691. PMID: 36119654; PMCID: PMC9465266.
Wise SK, Schlosser RJ. Subcutaneous and sublingual immunotherapy for allergic rhinitis: what is the evidence? Am J Rhinol Allergy. 2012 Jan-Feb;26(1):18-22. doi: 10.2500/ajra.2012.26.3691. PMID: 22391071; PMCID: PMC3906519.
Aboshady OA, Elghanam KM. Sublingual immunotherapy in allergic rhinitis: efficacy, safety, adherence and guidelines. ClinExpOtorhinolaryngol. 2014 Dec;7(4):241-9. doi: 10.3342/ceo.2014.7.4.241. Epub 2014 Nov 14. PMID: 25436040; PMCID: PMC4240478.
KeshavarzShahbaz S, Varasteh AR, Koushki K, Ayati SH, Mashayekhi K, Sadeghi M, Moghadam M, Sankian M. Sublingual dendritic cells targeting by aptamer: Possible approach for improvement of sublingual immunotherapy efficacy. IntImmunopharmacol. 2020 Aug;85:106603. doi: 10.1016/j.intimp.2020.106603. Epub 2020 May 30. PMID: 32485357.
Din L, Lui F. Butterbur. [Updated 2023 Jun 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537160/.
Abdelfattah Dse, Fouad Ma, Elmeshad An, El-Nabarawi Ma, Elhabal Sf. Anti-Obesity Nutraceuticals: Insights Into Mechanisms of Action And Potential Use of Biocompatible Nanocarriers for Delivery. Int J App Pharm. 2024 Jul. 7; 16(4):57-65.
Kocot J, Kiełczykowska M, Luchowska-Kocot D, Kurzepa J, Musik I. Antioxidant Potential of Propolis, Bee Pollen, and Royal Jelly: Possible Medical Application. Oxid Med Cell Longev. 2018 May 2;2018:7074209. doi: 10.1155/2018/7074209. PMID: 29854089; PMCID: PMC5954854.
H. Chaudhary, Rathee, P. ,Rathee, S. , and Kumar, V. , “Natural Relief for Allergies: An Overview”, Pharmacognosy Review, vol. 2, no. 4, pp. 241-248, 2008.
Thomet OA, Simon HU. Petasins in the treatment of allergic diseases: results of preclinical and clinical studies. Int Arch Allergy Immunol. 2002 Oct;129(2):108-12. doi: 10.1159/000065884. PMID: 12403927.
Kwak JE, Lee JY, Baek JY, Kim SW, Ahn MR. The Antioxidant and Anti-Inflammatory Properties of Bee Pollen from Acorn (QuercusacutissimaCarr.) and Darae (Actinidia arguta). Antioxidants (Basel). 2024 Aug 13;13(8):981. doi: 10.3390/antiox13080981. PMID: 39199227; PMCID: PMC11352170.
Momin MM, Kane S, Abhang P. Formulation and evaluation of bilayer tablet for bimodal release of venlafaxine hydrochloride. Front Pharmacol. 2015 Jul 9;6:144. doi: 10.3389/fphar.2015.00144. PMID: 26217229; PMCID: PMC4496574.
Shankrayya M, Kulakarni ST, Vinayaka DM, Sathwik, Sourav AK, Taj S and Rahul RPK: Formulation and evaluation of carbamazepine bilayer tablet for bimodal release. Int J Pharm Sci & Res 2023; 14(10): 5017-24. doi: 10.13040/IJPSR.0975-8232.14(10).5017-24.
Aghera, Nikunj & Shah, Suresh &Vadalia, Kantilal. (2012). Formulation and evaluation of sublingual tablets of losartan potassium. Asian Pacific Journal of Tropical Disease. 2. S130–S135. 10.1016/S2222-1808(12)60138-8.
Choudhury, Priyanka & Deb, Pulak & Dash, Suvakanta. (2016). Formulation and statistical optimization of bilayer sublingual tablets of Levocetirizine hydrochloride and Ambroxol hydrochloride. Asian Journal of Pharmaceutical and Clinical Research. 9. 228-234. 10.22159/ajpcr.2016.v9i5.13343
Prajapati ST, Patel PB, Patel CN. Formulation and evaluation of sublingual tablets containing Sumatriptan succinate. Int J Pharm Investig. 2012 Jul;2(3):162-8. doi: 10.4103/2230-973X.104400. PMID: 23373008; PMCID: PMC3555012
Bayrak Z, Tas C, Tasdemir U, Erol H, Ozkan CK, Savaser A, Ozkan Y. Formulation of zolmitriptan sublingual tablets prepared by direct compression with different polymers: in vitro and in vivo evaluation. Eur J Pharm Biopharm. 2011 Aug;78(3):499-505. doi: 10.1016/j.ejpb.2011.02.014. Epub 2011 Feb 23. PMID: 21352916
Muneeba Akhtar, Muhammad Jamshaid, Muhammad Zaman, Agha Zeeshan Mirza, Bilayer tablets: A developing novel drug delivery system, Journal of Drug Delivery Science and Technology, Volume 60, 2020, 102079, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2020.102079.
Desai PM, Er PX, Liew CV, Heng PW. Functionality of disintegrants and their mixtures in enabling fast disintegration of tablets by a quality by design approach. AAPS PharmSciTech. 2014 Oct;15(5):1093-104. doi: 10.1208/s12249-014-0137-4. Epub 2014 May 22. PMID: 24848762; PMCID: PMC4179650.
Nony E, Bouley J, Le Mignon M, Lemoine P, Jain K, Horiot S, Mascarell L, Pallardy M, Vincentelli R, Leone P, Roussel A, Batard T, Abiteboul K, Robin B, de Beaumont O, Arvidsson M, Rak S, Moingeon P. Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in birch pollen-allergic patients. Allergy. 2015 Jul;70(7):795-804. doi: 10.1111/all.12622. Epub 2015 Apr 20. PMID: 25846209.
Ryakala H, Dineshmohan S, Ramesh A, Gupta VR. Formulation and in vitro evaluation of bilayer tablets of nebivolol hydrochloride and nateglinide for the treatment of diabetes and hypertension. J Drug Deliv. 2015;2015:827859. doi: 10.1155/2015/827859. Epub 2015 Jan 14. PMID: 25648606; PMCID: PMC4310311.
Semalty M, Semalty A, Kumar G. Formulation and characterization of mucoadhesive buccal films of glipizide. Indian J Pharm Sci. 2008 Jan;70(1):43-8. doi: 10.4103/0250-474X.40330. PMID: 20390079; PMCID: PMC2852059.
Published
How to Cite
Issue
Section
Copyright (c) 2025 V. DEEPA KUMARI, G. SELVI, S. SHYAM SUNDAR, A. LAKSHMI PRIYA
This work is licensed under a Creative Commons Attribution 4.0 International License.
