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Experimental Design Supported Formulation and Evaluation of Nanostructured Lipid Carrier Loaded Oro mucosal Film of Tenofovir Disoproxil Fumarate

Yıl 2024, Cilt: 28 Sayı: 4, 940 - 951, 28.06.2025

Kavitha Hk Sayani Bhattacharyya

Öz

Antiretroviral medication tenofovir disoproxil fumarate (TDF) is frequently used to treat HIV and Hepatitis B virus infection and possesses low oral bioavailability due to low cellular penetration, and intestinal degradation. The present research focuses to develop nanoparticle-loaded oral film of TDF for the pediatric population with an aim to improve bioavailability and patient compliance. A high-shear homogenization process was employed to prepare nanostructured lipid carriers (NLCs) of TDF using an I-Optimal design. The consequences of proportions of solid and liquid lipid, and surfactant concentrations on drug entrapment, loading, and particle size were studied with a planned 14 experimental runs. The optimized formulation was loaded into an oromucosal film using hydroxy propyl methyl cellulose (HPMC) polymer. The films were evaluated for their physicochemical, and mechanical properties. The permeation of the drug from the films through goat oral mucosa was estimated. The design yielded an optimized product characterized by its nanosized (215 nm), stability (0.1 mV), and high entrapment (95.6%) of TDF in the carrier matrix. The surface morphology proved the irregular surface of the nano lipid carrier. The oro-mucosal film exhibited prolonged residence time and was released gradually over 24 h. The permeation of the drug from the nanocarriers loaded film was significantly improved compared to the pure drug. These findings support the idea that NLC-loaded oro-mucosal adhesive films may represent a promising strategy for increasing TDF's oral bioavailability.

Anahtar Kelimeler

Tenofovir Disoproxil Fumarate Nano lipid carriers High shear homogenization Oro mucosal adhesive film Solvent Casting method

Kaynakça

  • [1] Ray AS, Fordyce MW, Hitchcock MJM. Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of human immunodeficiency virus. Antiviral Res. 2016;125:63–70. https:// doi.org/10.1016/j.antiviral.2015.11.009
  • [2] Chauhan I, Yasir M, Verma M, Singh AP. Nanostructured lipid carriers: A groundbreaking approach for transdermal drug delivery. Adv Pharm Bull. 2020;10(2):150–165. https://doi.org/10.34172/apb.2020.021
  • [3] Basahih TS, Alamoudi AA, El-Say KM, Alhakamy NA, Ahmed OAA. Improved transmucosal delivery of glimepiride via unidirectional release buccal film loaded with vitamin e tpgs-based nanocarrier. Dose-Response. 2020;18(3): 1559325820945164. https://doi.org/10.1177/1559325820945164
  • [4] Haider M, Abdin SM, Kamal L, Orive G. Nanostructured lipid carriers for delivery of chemotherapeutics: A review. Pharmaceutics. 2020;12(3):1–26. https://doi.org/10.3390/pharmaceutics12030288
  • [5] Reddy HV R, Bhattacharyya S. Mucoadhesive buccal delivery of drugs- challenges and present aspects. Indian drugs. 2020;57(6):7-20. https://doi.org/10.53879/id.57.06.12294
  • [6] Reddy HV R, Bhattacharyya S. In vitro evaluation of mucoadhesive in situ nanogel of celecoxib for buccal delivery. Ann Pharm Fr. 2021;79(4):418–430. https://doi.org/10.1016/j.pharma.2021.01.006
  • [7] Alopaeus JF, Hellfritzsch M, Gutowski T, Scherließ R, Almeida A, Sarmento B, Natasa SB,Tho I. Mucoadhesive buccal films based on a graft co-polymer – A mucin-retentive hydrogel scaffold. Eur J Pharm Sci. 2020;142:105142. https://doi.org/10.1016/j.ejps.2019.105142
  • [8] Tenofovir disoproxil: uses, interactions, mechanism of action | DrugBank Online. https://doi.org/10.1016/j.ejps.2019.105142
  • [9] Khan AB, Thakur RS. Formulation and evaluation of mucoadhesive microspheres of tenofovir disoproxil fumarate for intravaginal use. Curr Drug Del. 2014;11(1):112-122. https://doi.org/ 10.2174/156720181000131028120709
  • [10] Patel D, Dasgupta S, Dey S, Ramani YR, Ray S, Mazumder B. Nanostructured Lipid Carriers (NLC)-based gel for the topical delivery of aceclofenac: Preparation, characterization, and in vivo evaluation. Sci Pharm. 2012;80(3):749-764. http://dx.doi.org/10.3797/scipharm.1202-12
  • [11] Alhayali A, Rao PV, Velaga S. Silodosin oral films: Development, physico-mechanical properties and in vitro dissolution studies in simulated saliva. J Drug Del Sci Tech. 2019:53:101122. https://doi.org/ 10.1016/j.jddst.2019.06.019.
  • [12] Dhawale P, Mahajan NM, Mahapatra DK, Mahajan UN, Gangane PS. HPMC K15M and Carbopol 940 mediated fabrication of ondansetron hydrochloride intranasal mucoadhesive microspheres. J Appl Pharm Sci. 2018;8(08): 075-083. https://doi.org/ 10.7324/JAPS.2018.8812
  • [13] Kovačević AB, Müller RH, Keck CM. Formulation development of lipid nanoparticles: Improved lipid screening and development of tacrolimus loaded nanostructured lipid carriers (NLC). Int J Pharm. 2020;576:118918. https://doi.org/10.1016/j.ijpharm.2019.118918
  • [14] Jafarifar Z, Rezaie M, Sharifan P, Jahani V, Daneshmand S, Ghazizadeh H, Ferns GA, Shiva G, Majid GM. Preparation and characterization of nanostructured lipid carrier (NLC) and nanoemulsion containing vitamin d3. Appl Bıochem Bıotechnol. 2022;194(2):914–929. https://doi.org/10.1007/s12010-021-03656-z
  • [15] Harshitha C, Bhattacharyya S. Statistical optimization amalgamated approach on formulation development of nano lipid carrier loaded hydrophilic gel of fluticasone propionate. Indian J Pharm Edu Res. 2021;55(2):1–10. https://doi.org/ 10.5530/ijper.55.2.79
  • [16] Liu D, Liu Z, Wang L, Zhang C, Zhang N. Nanostructured lipid carriers as novel carrier for parenteral delivery of docetaxel. Colloids and Surf B: Biointerfaces. 2011;85(2):262–269. https://doi.org/10.1016/j.colsurfb.2011.02.038
  • [17] Yaghoubi A, Ghojazadeh M, Abolhasani S, Alikhah H, Khaki-Khatibi F. Correlation of serum levels of vitronectin, malondialdehyde and hs-crp with disease severity in coronary artery disease. J Cardiovasc Thorac Res. 2015;7(3):113–117. https://doi.org/10.15171%2Fjcvtr.2015.24
  • [18] Guilherme VA, Ribeiro LNM, Alcântara ACS, Castro SR, Rodrigues da Silva GH, da Silva CG, Marcia CB, Juliana CN, Dristina GM, Abdalla HB,Bonfante R,Cereda CMS, Paula ED. Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration. Sci Rep. 2019;9(1):1–11. https://doi.org/10.1038/s41598-019-47486-w
  • [19] Pi J, Wang S, Li W, Kebebe D, Zhang Y, Zhang B. Qi D, Guo P, Li N, Liu Z. A nano-cocrystal strategy to improve the dissolution rate and oral bioavailability of baicalein. Asian J Pharm Sci. 2019; 14:154–164. https://doi.org/10.1016/j.ajps.2018.04.009
  • [20] Takeuchi K, Watanabe M, Yanagi M, Murakami I, Hosono H, Nishizawa S, Chigono Y, Hirabayashi S, Matsuda J, Yamaoka K, Inoue K. In vitro and clinical evaluation of an oral mucosal adhesive film containing indomethacin. Yakugaku Zasshi. 2008;128(12):1791–1795. https://doi.org/10.1248/yakushi.128.1791
  • [21] Bhattacharyya S, RangaRao BG. Formulation and development of oral disintegrating film of fexofenadine hydrochloride. Acta Pharm Sci. 2022;60 (4):345–362. https://doi.org/ 10.23893/1307-2080.APS6023
  • [22] Havele S, Dhaneshwar S. Stress studies of tenofovir disoproxil fumarate by HPTLC in bulk drug and pharmaceutical formulation. Sci World J.2012;894136. https://doi.org/10.1100/2012/894136
  • [23] Mahajan HS, Deshmukh SR. Development and evaluation of gel-forming ocular films based on xyloglucan. Carbohydr Polym. 2015;122:243–247. https://doi.org/10.1016/j.carbpol
  • [24] Preis M, Woertz C, Kleinebudde P, Breitkreutz J. Oromucosal film preparations: Classification and characterization methods. Expert Opin Drug Deliv. 2013;10(9):1303–1317. https://doi.org/10.1517/17425247.2013.804058
  • [25] Mahboob MBH, Riaz T, Jamshaid M, Bashir I, Zulfiqar S. Oral films: A comprehensive review. Int Cur Pharm J. 2016;5(12):111–117. https://doi.org/10.3329/icpj.v5i12.30413
  • [26] Satishbabu B, Srinivasan B. Preparation and evaluation of buccoadhesive films of atenolol. Indian J Pharm Sci. 2008;70(2):175–179. https://doi.org/10.4103%2F0250-474X.41451.
  • [27] Jovanović M, Tomić N, Cvijić S, Stojanović D, Ibrić S, Uskoković P. Mucoadhesive gelatin buccal films with propranolol hydrochloride: Evaluation of mechanical, mucoadhesive, and biopharmaceutical properties. Pharmaceutics. 2021;13(2):1–19. https://doi.org/10.3390/pharmaceutics13020273
  • [28] Gaba B, Fazil M, Khan S, Ali A, Baboota S, Ali J. Nanostructured lipid carrier system for topical delivery of terbinafine hydrochloride. Bull Fac Pharm. 2015;53(2):147–159. https://doi.org/10.1016/j.bfopcu.2015.10.001
  • [29] Kamble RN, Mehtre R V., Mehta PP, Nangare P, Patil SS. Albendazole electrospun nanofiber films: in-vitro and ex-vivo assessment. Bionanoscience. 2019;9(3):625–636. https://doi.org/10.1007/s12668-019-00627-x

Yıl 2024, Cilt: 28 Sayı: 4, 940 - 951, 28.06.2025

Kavitha Hk Sayani Bhattacharyya

Öz

Kaynakça

  • [1] Ray AS, Fordyce MW, Hitchcock MJM. Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of human immunodeficiency virus. Antiviral Res. 2016;125:63–70. https:// doi.org/10.1016/j.antiviral.2015.11.009
  • [2] Chauhan I, Yasir M, Verma M, Singh AP. Nanostructured lipid carriers: A groundbreaking approach for transdermal drug delivery. Adv Pharm Bull. 2020;10(2):150–165. https://doi.org/10.34172/apb.2020.021
  • [3] Basahih TS, Alamoudi AA, El-Say KM, Alhakamy NA, Ahmed OAA. Improved transmucosal delivery of glimepiride via unidirectional release buccal film loaded with vitamin e tpgs-based nanocarrier. Dose-Response. 2020;18(3): 1559325820945164. https://doi.org/10.1177/1559325820945164
  • [4] Haider M, Abdin SM, Kamal L, Orive G. Nanostructured lipid carriers for delivery of chemotherapeutics: A review. Pharmaceutics. 2020;12(3):1–26. https://doi.org/10.3390/pharmaceutics12030288
  • [5] Reddy HV R, Bhattacharyya S. Mucoadhesive buccal delivery of drugs- challenges and present aspects. Indian drugs. 2020;57(6):7-20. https://doi.org/10.53879/id.57.06.12294
  • [6] Reddy HV R, Bhattacharyya S. In vitro evaluation of mucoadhesive in situ nanogel of celecoxib for buccal delivery. Ann Pharm Fr. 2021;79(4):418–430. https://doi.org/10.1016/j.pharma.2021.01.006
  • [7] Alopaeus JF, Hellfritzsch M, Gutowski T, Scherließ R, Almeida A, Sarmento B, Natasa SB,Tho I. Mucoadhesive buccal films based on a graft co-polymer – A mucin-retentive hydrogel scaffold. Eur J Pharm Sci. 2020;142:105142. https://doi.org/10.1016/j.ejps.2019.105142
  • [8] Tenofovir disoproxil: uses, interactions, mechanism of action | DrugBank Online. https://doi.org/10.1016/j.ejps.2019.105142
  • [9] Khan AB, Thakur RS. Formulation and evaluation of mucoadhesive microspheres of tenofovir disoproxil fumarate for intravaginal use. Curr Drug Del. 2014;11(1):112-122. https://doi.org/ 10.2174/156720181000131028120709
  • [10] Patel D, Dasgupta S, Dey S, Ramani YR, Ray S, Mazumder B. Nanostructured Lipid Carriers (NLC)-based gel for the topical delivery of aceclofenac: Preparation, characterization, and in vivo evaluation. Sci Pharm. 2012;80(3):749-764. http://dx.doi.org/10.3797/scipharm.1202-12
  • [11] Alhayali A, Rao PV, Velaga S. Silodosin oral films: Development, physico-mechanical properties and in vitro dissolution studies in simulated saliva. J Drug Del Sci Tech. 2019:53:101122. https://doi.org/ 10.1016/j.jddst.2019.06.019.
  • [12] Dhawale P, Mahajan NM, Mahapatra DK, Mahajan UN, Gangane PS. HPMC K15M and Carbopol 940 mediated fabrication of ondansetron hydrochloride intranasal mucoadhesive microspheres. J Appl Pharm Sci. 2018;8(08): 075-083. https://doi.org/ 10.7324/JAPS.2018.8812
  • [13] Kovačević AB, Müller RH, Keck CM. Formulation development of lipid nanoparticles: Improved lipid screening and development of tacrolimus loaded nanostructured lipid carriers (NLC). Int J Pharm. 2020;576:118918. https://doi.org/10.1016/j.ijpharm.2019.118918
  • [14] Jafarifar Z, Rezaie M, Sharifan P, Jahani V, Daneshmand S, Ghazizadeh H, Ferns GA, Shiva G, Majid GM. Preparation and characterization of nanostructured lipid carrier (NLC) and nanoemulsion containing vitamin d3. Appl Bıochem Bıotechnol. 2022;194(2):914–929. https://doi.org/10.1007/s12010-021-03656-z
  • [15] Harshitha C, Bhattacharyya S. Statistical optimization amalgamated approach on formulation development of nano lipid carrier loaded hydrophilic gel of fluticasone propionate. Indian J Pharm Edu Res. 2021;55(2):1–10. https://doi.org/ 10.5530/ijper.55.2.79
  • [16] Liu D, Liu Z, Wang L, Zhang C, Zhang N. Nanostructured lipid carriers as novel carrier for parenteral delivery of docetaxel. Colloids and Surf B: Biointerfaces. 2011;85(2):262–269. https://doi.org/10.1016/j.colsurfb.2011.02.038
  • [17] Yaghoubi A, Ghojazadeh M, Abolhasani S, Alikhah H, Khaki-Khatibi F. Correlation of serum levels of vitronectin, malondialdehyde and hs-crp with disease severity in coronary artery disease. J Cardiovasc Thorac Res. 2015;7(3):113–117. https://doi.org/10.15171%2Fjcvtr.2015.24
  • [18] Guilherme VA, Ribeiro LNM, Alcântara ACS, Castro SR, Rodrigues da Silva GH, da Silva CG, Marcia CB, Juliana CN, Dristina GM, Abdalla HB,Bonfante R,Cereda CMS, Paula ED. Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration. Sci Rep. 2019;9(1):1–11. https://doi.org/10.1038/s41598-019-47486-w
  • [19] Pi J, Wang S, Li W, Kebebe D, Zhang Y, Zhang B. Qi D, Guo P, Li N, Liu Z. A nano-cocrystal strategy to improve the dissolution rate and oral bioavailability of baicalein. Asian J Pharm Sci. 2019; 14:154–164. https://doi.org/10.1016/j.ajps.2018.04.009
  • [20] Takeuchi K, Watanabe M, Yanagi M, Murakami I, Hosono H, Nishizawa S, Chigono Y, Hirabayashi S, Matsuda J, Yamaoka K, Inoue K. In vitro and clinical evaluation of an oral mucosal adhesive film containing indomethacin. Yakugaku Zasshi. 2008;128(12):1791–1795. https://doi.org/10.1248/yakushi.128.1791
  • [21] Bhattacharyya S, RangaRao BG. Formulation and development of oral disintegrating film of fexofenadine hydrochloride. Acta Pharm Sci. 2022;60 (4):345–362. https://doi.org/ 10.23893/1307-2080.APS6023
  • [22] Havele S, Dhaneshwar S. Stress studies of tenofovir disoproxil fumarate by HPTLC in bulk drug and pharmaceutical formulation. Sci World J.2012;894136. https://doi.org/10.1100/2012/894136
  • [23] Mahajan HS, Deshmukh SR. Development and evaluation of gel-forming ocular films based on xyloglucan. Carbohydr Polym. 2015;122:243–247. https://doi.org/10.1016/j.carbpol
  • [24] Preis M, Woertz C, Kleinebudde P, Breitkreutz J. Oromucosal film preparations: Classification and characterization methods. Expert Opin Drug Deliv. 2013;10(9):1303–1317. https://doi.org/10.1517/17425247.2013.804058
  • [25] Mahboob MBH, Riaz T, Jamshaid M, Bashir I, Zulfiqar S. Oral films: A comprehensive review. Int Cur Pharm J. 2016;5(12):111–117. https://doi.org/10.3329/icpj.v5i12.30413
  • [26] Satishbabu B, Srinivasan B. Preparation and evaluation of buccoadhesive films of atenolol. Indian J Pharm Sci. 2008;70(2):175–179. https://doi.org/10.4103%2F0250-474X.41451.
  • [27] Jovanović M, Tomić N, Cvijić S, Stojanović D, Ibrić S, Uskoković P. Mucoadhesive gelatin buccal films with propranolol hydrochloride: Evaluation of mechanical, mucoadhesive, and biopharmaceutical properties. Pharmaceutics. 2021;13(2):1–19. https://doi.org/10.3390/pharmaceutics13020273
  • [28] Gaba B, Fazil M, Khan S, Ali A, Baboota S, Ali J. Nanostructured lipid carrier system for topical delivery of terbinafine hydrochloride. Bull Fac Pharm. 2015;53(2):147–159. https://doi.org/10.1016/j.bfopcu.2015.10.001
  • [29] Kamble RN, Mehtre R V., Mehta PP, Nangare P, Patil SS. Albendazole electrospun nanofiber films: in-vitro and ex-vivo assessment. Bionanoscience. 2019;9(3):625–636. https://doi.org/10.1007/s12668-019-00627-x
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İlaç Dağıtım Teknolojileri
Bölüm Articles
Yazarlar

Kavitha Hk 0000-0002-4163-2413

Sayani Bhattacharyya 0000-0002-4013-4316

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2024 Cilt: 28 Sayı: 4

Kaynak Göster

APA Hk, K., & Bhattacharyya, S. (2025). Experimental Design Supported Formulation and Evaluation of Nanostructured Lipid Carrier Loaded Oro mucosal Film of Tenofovir Disoproxil Fumarate. Journal of Research in Pharmacy, 28(4), 940-951.
AMA Hk K, Bhattacharyya S. Experimental Design Supported Formulation and Evaluation of Nanostructured Lipid Carrier Loaded Oro mucosal Film of Tenofovir Disoproxil Fumarate. J. Res. Pharm. Temmuz 2025;28(4):940-951.
Chicago Hk, Kavitha, ve Sayani Bhattacharyya. “Experimental Design Supported Formulation and Evaluation of Nanostructured Lipid Carrier Loaded Oro Mucosal Film of Tenofovir Disoproxil Fumarate”. Journal of Research in Pharmacy 28, sy. 4 (Temmuz 2025): 940-51.
EndNote Hk K, Bhattacharyya S (01 Temmuz 2025) Experimental Design Supported Formulation and Evaluation of Nanostructured Lipid Carrier Loaded Oro mucosal Film of Tenofovir Disoproxil Fumarate. Journal of Research in Pharmacy 28 4 940–951.
IEEE K. Hk ve S. Bhattacharyya, “Experimental Design Supported Formulation and Evaluation of Nanostructured Lipid Carrier Loaded Oro mucosal Film of Tenofovir Disoproxil Fumarate”, J. Res. Pharm., c. 28, sy. 4, ss. 940–951, 2025.
ISNAD Hk, Kavitha - Bhattacharyya, Sayani. “Experimental Design Supported Formulation and Evaluation of Nanostructured Lipid Carrier Loaded Oro Mucosal Film of Tenofovir Disoproxil Fumarate”. Journal of Research in Pharmacy 28/4 (Temmuz 2025), 940-951.
JAMA Hk K, Bhattacharyya S. Experimental Design Supported Formulation and Evaluation of Nanostructured Lipid Carrier Loaded Oro mucosal Film of Tenofovir Disoproxil Fumarate. J. Res. Pharm. 2025;28:940–951.
MLA Hk, Kavitha ve Sayani Bhattacharyya. “Experimental Design Supported Formulation and Evaluation of Nanostructured Lipid Carrier Loaded Oro Mucosal Film of Tenofovir Disoproxil Fumarate”. Journal of Research in Pharmacy, c. 28, sy. 4, 2025, ss. 940-51.
Vancouver Hk K, Bhattacharyya S. Experimental Design Supported Formulation and Evaluation of Nanostructured Lipid Carrier Loaded Oro mucosal Film of Tenofovir Disoproxil Fumarate. J. Res. Pharm. 2025;28(4):940-51.