TY  - 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 . .

TY  - CONF
AU  - Kurćubić, Ivana
AU  - Vajić, Una‐Jovana
AU  - Cvijić, Sandra
AU  - Crevar-Sakač, Milkica
AU  - Ibrić, Svetlana
AU  - Miloradović, Zoran
AU  - Mihailović‐Stanojević, Nevena
AU  - Ivanov, Milan
AU  - Karanović, Danijela
AU  - Jovović, Đurđica
AU  - Đuriš, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4512
AB  - Mucoadhesive buccal films can improve drug absorption by prolonging its retention
time on the buccal mucosa (1). The aim of the study was a comparative assessment of the
hemodynamic effects and pharmacokinetics of propranolol hydrochloride (PROP) after
buccal and oral administration in spontaneously hypertensive rats. Animals were divided
into 3 groups: Group I (control) received 0.5 mL of water with a gastric tube, group II
received an immediate-release 10 mg PROP tablet via gastric tube, and group III received a
mucoadhesive 10 mg PROP buccal film. Systolic (SP) and diastolic blood pressure (DP), and
heart rate (SF) were measured in rats, and pharmacokinetic PROP parameters, Cmax, tmax,
and AUC0 → 24, were calculated by noncompartmental analysis. Mucoadhesive buccal films
showed superior degree of absorption of PROP over immediate-release tablets (AUC0 → 24:
69.64 μgh/ml versus 24.61 μgh/ml). The tmax value was significantly higher in
mucoadhesive buccal films, which indicates a prolonged PROP release and longer
therapeutic effect (71.19h versus 29.73h). There was no statistically significant difference in
Cmax values between groups II and III of rats (4.74 μg ml versus 7.11 μg ml). Mucoadhesive
buccal films provide a more pronounced and long-lasting reduction primarily of SF
(reduction of 28-51% lasting from 10 minutes to the twelfth hour of testing), but also SP and
DP (between 15-30% from the first to the sixth hour of testing) compared to immediate-
release tablets. Mucoadhesive buccal films allow bypass/reduction of the extensive hepatic
first-pass metabolism, and consequently improve the therapeutic PROP effect.
AB  - Mukoadhezivni bukalni filmovi mogu poboljšati apsorpciju lekovite supstance
produžavajuć i vreme zadržavanja lekovitog preparata na bukalnoj sluznici (1). Cilj studije je
bila komparativna procena hemodinamskih efekata i farmakokinetike propranolol-
hidrohlorida (PROP) nakon bukalne i peroralne primene kod sponatano hipertenzivnih
pacova. Spontano hipertenzivni pacovi su podeljeni u 3 grupe: I (kontrolna) grupa je dobila
0,5 mL vode gastričnom sondom, II grupa je dobila tabletu sa trenutnim oslobađanjem sa 10
mg PROP gastričnom sondom i III grupa je dobila mukoadhezivni bukalni film sa 10 mg
PROP. Filmovi su pripremljeni korišćenjem polietilenoksida, hidroksipropilmetilceluloze i
polivinilalkohola kao film-formirajućih polimera sa mukoadhezivnim svojstvima. Pacovima
su mereni sistolni (SP) i dijastolni krvni pritisak (DP), srčana frekvencija (SF), a
neprostornom farmakokinetičkom analizom izračunati su parametri PROP: Cmax, t max i
AUC0→24 . Mukoadhezivni bukalni filmovi su pokazali superiornost u odnosu na tablete sa
trenutnim oslobađanjem u pogledu stepena apsorpcije PROP (AUC 0→24 : 69,64 μgh/ml
naspram 24,61 μgh/ml). Tmax vrednost je bila značajno veća kod mukoadhezivnih bukalnih
filmova što ukazuje na produženo oslobađanje PROP i duži terapijski efekat (71,19 h
naspram 29,73 h). Između II i II grupe pacova nema statistički značajne razlike u
vrednostima Cmax (4,74 μg/ml naspram 7,11 μg/ml). Mukoadhezivni bukalni filmovi izazivaju
izraženije i dugotrajnije smanjenje pre svega SF (smanjenje od 28-51% u trajanju od 10
minuta do dvanaestog sata ispitivanja), ali i SP i DP (između 15-30% od prvog do šestog sata
ispitivanja) u odnosu na tablete sa trenutnim oslobađanjem. Pripremljeni mukoadhezivni
bukalni filmovi omogućavaju zaobilazak/smanjenje ekstenzivnog metabolizma prvog
prolaza kroz jetru i posledično poboljšavaju terapijski efekat PROP.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension
T1  - Efekti akutne primene mukoadhezivnih bukalnih filmova sa propranolol‐hidrohloridom u animalnom modelu esencijalne hipertenzije
VL  - 72
IS  - 4 suplement
SP  - S235
EP  - S236
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4512
ER  - 

@conference{
author = "Kurćubić, Ivana and Vajić, Una‐Jovana and Cvijić, Sandra and Crevar-Sakač, Milkica and Ibrić, Svetlana and Miloradović, Zoran and Mihailović‐Stanojević, Nevena and Ivanov, Milan and Karanović, Danijela and Jovović, Đurđica and Đuriš, Jelena",
year = "2022",
abstract = "Mucoadhesive buccal films can improve drug absorption by prolonging its retention
time on the buccal mucosa (1). The aim of the study was a comparative assessment of the
hemodynamic effects and pharmacokinetics of propranolol hydrochloride (PROP) after
buccal and oral administration in spontaneously hypertensive rats. Animals were divided
into 3 groups: Group I (control) received 0.5 mL of water with a gastric tube, group II
received an immediate-release 10 mg PROP tablet via gastric tube, and group III received a
mucoadhesive 10 mg PROP buccal film. Systolic (SP) and diastolic blood pressure (DP), and
heart rate (SF) were measured in rats, and pharmacokinetic PROP parameters, Cmax, tmax,
and AUC0 → 24, were calculated by noncompartmental analysis. Mucoadhesive buccal films
showed superior degree of absorption of PROP over immediate-release tablets (AUC0 → 24:
69.64 μgh/ml versus 24.61 μgh/ml). The tmax value was significantly higher in
mucoadhesive buccal films, which indicates a prolonged PROP release and longer
therapeutic effect (71.19h versus 29.73h). There was no statistically significant difference in
Cmax values between groups II and III of rats (4.74 μg ml versus 7.11 μg ml). Mucoadhesive
buccal films provide a more pronounced and long-lasting reduction primarily of SF
(reduction of 28-51% lasting from 10 minutes to the twelfth hour of testing), but also SP and
DP (between 15-30% from the first to the sixth hour of testing) compared to immediate-
release tablets. Mucoadhesive buccal films allow bypass/reduction of the extensive hepatic
first-pass metabolism, and consequently improve the therapeutic PROP effect., Mukoadhezivni bukalni filmovi mogu poboljšati apsorpciju lekovite supstance
produžavajuć i vreme zadržavanja lekovitog preparata na bukalnoj sluznici (1). Cilj studije je
bila komparativna procena hemodinamskih efekata i farmakokinetike propranolol-
hidrohlorida (PROP) nakon bukalne i peroralne primene kod sponatano hipertenzivnih
pacova. Spontano hipertenzivni pacovi su podeljeni u 3 grupe: I (kontrolna) grupa je dobila
0,5 mL vode gastričnom sondom, II grupa je dobila tabletu sa trenutnim oslobađanjem sa 10
mg PROP gastričnom sondom i III grupa je dobila mukoadhezivni bukalni film sa 10 mg
PROP. Filmovi su pripremljeni korišćenjem polietilenoksida, hidroksipropilmetilceluloze i
polivinilalkohola kao film-formirajućih polimera sa mukoadhezivnim svojstvima. Pacovima
su mereni sistolni (SP) i dijastolni krvni pritisak (DP), srčana frekvencija (SF), a
neprostornom farmakokinetičkom analizom izračunati su parametri PROP: Cmax, t max i
AUC0→24 . Mukoadhezivni bukalni filmovi su pokazali superiornost u odnosu na tablete sa
trenutnim oslobađanjem u pogledu stepena apsorpcije PROP (AUC 0→24 : 69,64 μgh/ml
naspram 24,61 μgh/ml). Tmax vrednost je bila značajno veća kod mukoadhezivnih bukalnih
filmova što ukazuje na produženo oslobađanje PROP i duži terapijski efekat (71,19 h
naspram 29,73 h). Između II i II grupe pacova nema statistički značajne razlike u
vrednostima Cmax (4,74 μg/ml naspram 7,11 μg/ml). Mukoadhezivni bukalni filmovi izazivaju
izraženije i dugotrajnije smanjenje pre svega SF (smanjenje od 28-51% u trajanju od 10
minuta do dvanaestog sata ispitivanja), ali i SP i DP (između 15-30% od prvog do šestog sata
ispitivanja) u odnosu na tablete sa trenutnim oslobađanjem. Pripremljeni mukoadhezivni
bukalni filmovi omogućavaju zaobilazak/smanjenje ekstenzivnog metabolizma prvog
prolaza kroz jetru i posledično poboljšavaju terapijski efekat PROP.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension, Efekti akutne primene mukoadhezivnih bukalnih filmova sa propranolol‐hidrohloridom u animalnom modelu esencijalne hipertenzije",
volume = "72",
number = "4 suplement",
pages = "S235-S236",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4512"
}

Kurćubić, I., Vajić, U., Cvijić, S., Crevar-Sakač, M., Ibrić, S., Miloradović, Z., Mihailović‐Stanojević, N., Ivanov, M., Karanović, D., Jovović, Đ.,& Đuriš, J.. (2022). Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S235-S236.
https://hdl.handle.net/21.15107/rcub_farfar_4512

Kurćubić I, Vajić U, Cvijić S, Crevar-Sakač M, Ibrić S, Miloradović Z, Mihailović‐Stanojević N, Ivanov M, Karanović D, Jovović Đ, Đuriš J. Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension. in Arhiv za farmaciju. 2022;72(4 suplement):S235-S236.
https://hdl.handle.net/21.15107/rcub_farfar_4512 .

Kurćubić, Ivana, Vajić, Una‐Jovana, Cvijić, Sandra, Crevar-Sakač, Milkica, Ibrić, Svetlana, Miloradović, Zoran, Mihailović‐Stanojević, Nevena, Ivanov, Milan, Karanović, Danijela, Jovović, Đurđica, Đuriš, Jelena, "Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S235-S236,
https://hdl.handle.net/21.15107/rcub_farfar_4512 .