Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films
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2023
Authors
Kurćubić, Ivana
Đuriš, Jelena

Cvijić, Sandra

Crevar, Milkica

Ibrić, Svetlana

Miloradović, Zoran
Mihailović-Stanojević, Nevena
Karanović, Danijela
Ivanov, Milan
Jovović, Đurđica
Vajić, Una-Jovana
Article (Published version)

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In order to exploit the advantage of drug delivery through the buccal mucosa, mucoadhesive buccal films with propranolol hydrochloride based on polyethylene oxide, hydroxypropyl methylcellulose, and polyvinyl alcohol have been developed. The aim of this study was the development, pharmaceutical-technological (uniformity of mass and drug content, film thickness, potential interactions between polymers and propranolol hydrochloride, in vitro drug permeation and drug release, mechanical and mucoadhesive properties), and biopharmaceutical characterization of prepared mucoadhesive buccal films through conducting in vivo study in spontaneously hypertensive rats and in silico modeling of intraoral and gastrointestinal drug absorption. For in vivo study formulation F2 (hydroxypropylmethyl cellulose 0.5%, polyethylene oxide 3.5%, polyvinyl alcohol 1.5%, propylene glycol 3%, and propranolol hydrochloride 2%) was selected, which showed the highest values of tensile strength and percentage of elon...gation, as well as the highest value of the force of adhesion. Results of pharmacokinetic in rats and in silico modeling confirmed the superiority of the mucoadhesive buccal films over immediate-release tablets (in rats: AUC0→24h 66.13 ± 18.03 vs. 24.61 ± 5.52 μg⋅h/mL, AUC0→∞ 111.82 ± 39.04 vs. 47.85 ± 11.67 μg⋅h/mL; in silico: AUC0→24h 200.17 vs.74.58 ng⋅h/mL, AUC0→∞ 204.04 vs. 75.64 ng⋅h/mL). Hemodynamic measurements have shown that mucoadhesive buccal films, compared to immediate-release tablets, provide a more pronounced decrease primarily in heart rate (28-51%), but also in diastolic pressure (up to 33%), as well as a longer heart rate reduction that was maintained for up to 12th h. Therefore, mucoadhesive buccal films increased the degree of absorbed drug and thus contributed to better therapeutic outcomes compared to immediate-release tablets for peroral administration.
Keywords:
Spontaneously hypertensive rats / Hemodynamic measurements / Mucoadhesive buccal film / Pharmacokinetic / Propranolol hydrochlorideSource:
Journal of Drug Delivery Science and Technology, 2023, 86Publisher:
- Elsevier
Funding / projects:
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200161 (University of Belgrade, Faculty of Pharmacy) (RS-200161)
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200015 (University of Belgrade, Institute for Medical Research) (RS-200015)
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- Editions de Sante
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PharmacyTY - JOUR AU - Kurćubić, Ivana AU - Đuriš, Jelena AU - Cvijić, Sandra AU - Crevar, Milkica AU - Ibrić, Svetlana AU - Miloradović, Zoran AU - Mihailović-Stanojević, Nevena AU - Karanović, Danijela AU - Ivanov, Milan AU - Jovović, Đurđica AU - Vajić, Una-Jovana PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4932 AB - In order to exploit the advantage of drug delivery through the buccal mucosa, mucoadhesive buccal films with propranolol hydrochloride based on polyethylene oxide, hydroxypropyl methylcellulose, and polyvinyl alcohol have been developed. The aim of this study was the development, pharmaceutical-technological (uniformity of mass and drug content, film thickness, potential interactions between polymers and propranolol hydrochloride, in vitro drug permeation and drug release, mechanical and mucoadhesive properties), and biopharmaceutical characterization of prepared mucoadhesive buccal films through conducting in vivo study in spontaneously hypertensive rats and in silico modeling of intraoral and gastrointestinal drug absorption. For in vivo study formulation F2 (hydroxypropylmethyl cellulose 0.5%, polyethylene oxide 3.5%, polyvinyl alcohol 1.5%, propylene glycol 3%, and propranolol hydrochloride 2%) was selected, which showed the highest values of tensile strength and percentage of elongation, as well as the highest value of the force of adhesion. Results of pharmacokinetic in rats and in silico modeling confirmed the superiority of the mucoadhesive buccal films over immediate-release tablets (in rats: AUC0→24h 66.13 ± 18.03 vs. 24.61 ± 5.52 μg⋅h/mL, AUC0→∞ 111.82 ± 39.04 vs. 47.85 ± 11.67 μg⋅h/mL; in silico: AUC0→24h 200.17 vs.74.58 ng⋅h/mL, AUC0→∞ 204.04 vs. 75.64 ng⋅h/mL). Hemodynamic measurements have shown that mucoadhesive buccal films, compared to immediate-release tablets, provide a more pronounced decrease primarily in heart rate (28-51%), but also in diastolic pressure (up to 33%), as well as a longer heart rate reduction that was maintained for up to 12th h. Therefore, mucoadhesive buccal films increased the degree of absorbed drug and thus contributed to better therapeutic outcomes compared to immediate-release tablets for peroral administration. PB - Elsevier T2 - Journal of Drug Delivery Science and Technology T1 - Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films VL - 86 DO - 10.1016/j.jddst.2023.104715 ER -
@article{ author = "Kurćubić, Ivana and Đuriš, Jelena and Cvijić, Sandra and Crevar, Milkica and Ibrić, Svetlana and Miloradović, Zoran and Mihailović-Stanojević, Nevena and Karanović, Danijela and Ivanov, Milan and Jovović, Đurđica and Vajić, Una-Jovana", year = "2023", abstract = "In order to exploit the advantage of drug delivery through the buccal mucosa, mucoadhesive buccal films with propranolol hydrochloride based on polyethylene oxide, hydroxypropyl methylcellulose, and polyvinyl alcohol have been developed. The aim of this study was the development, pharmaceutical-technological (uniformity of mass and drug content, film thickness, potential interactions between polymers and propranolol hydrochloride, in vitro drug permeation and drug release, mechanical and mucoadhesive properties), and biopharmaceutical characterization of prepared mucoadhesive buccal films through conducting in vivo study in spontaneously hypertensive rats and in silico modeling of intraoral and gastrointestinal drug absorption. For in vivo study formulation F2 (hydroxypropylmethyl cellulose 0.5%, polyethylene oxide 3.5%, polyvinyl alcohol 1.5%, propylene glycol 3%, and propranolol hydrochloride 2%) was selected, which showed the highest values of tensile strength and percentage of elongation, as well as the highest value of the force of adhesion. Results of pharmacokinetic in rats and in silico modeling confirmed the superiority of the mucoadhesive buccal films over immediate-release tablets (in rats: AUC0→24h 66.13 ± 18.03 vs. 24.61 ± 5.52 μg⋅h/mL, AUC0→∞ 111.82 ± 39.04 vs. 47.85 ± 11.67 μg⋅h/mL; in silico: AUC0→24h 200.17 vs.74.58 ng⋅h/mL, AUC0→∞ 204.04 vs. 75.64 ng⋅h/mL). Hemodynamic measurements have shown that mucoadhesive buccal films, compared to immediate-release tablets, provide a more pronounced decrease primarily in heart rate (28-51%), but also in diastolic pressure (up to 33%), as well as a longer heart rate reduction that was maintained for up to 12th h. Therefore, mucoadhesive buccal films increased the degree of absorbed drug and thus contributed to better therapeutic outcomes compared to immediate-release tablets for peroral administration.", publisher = "Elsevier", journal = "Journal of Drug Delivery Science and Technology", title = "Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films", volume = "86", doi = "10.1016/j.jddst.2023.104715" }
Kurćubić, I., Đuriš, J., Cvijić, S., Crevar, M., Ibrić, S., Miloradović, Z., Mihailović-Stanojević, N., Karanović, D., Ivanov, M., Jovović, Đ.,& Vajić, U.. (2023). Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films. in Journal of Drug Delivery Science and Technology Elsevier., 86. https://doi.org/10.1016/j.jddst.2023.104715
Kurćubić I, Đuriš J, Cvijić S, Crevar M, Ibrić S, Miloradović Z, Mihailović-Stanojević N, Karanović D, Ivanov M, Jovović Đ, Vajić U. Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films. in Journal of Drug Delivery Science and Technology. 2023;86. doi:10.1016/j.jddst.2023.104715 .
Kurćubić, Ivana, Đuriš, Jelena, Cvijić, Sandra, Crevar, Milkica, Ibrić, Svetlana, Miloradović, Zoran, Mihailović-Stanojević, Nevena, Karanović, Danijela, Ivanov, Milan, Jovović, Đurđica, Vajić, Una-Jovana, "Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films" in Journal of Drug Delivery Science and Technology, 86 (2023), https://doi.org/10.1016/j.jddst.2023.104715 . .