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1.
AAPS PharmSciTech ; 25(2): 34, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332233

RESUMO

Pravastatin sodium (PVS) is a hypolipidemic drug with poor oral bioavailability due to the first-pass effect. Therefore, this study aims to formulate and evaluate transdermal patches containing PVS-loaded nanoemulsions (PVS-NEs) to increase PVS's hypolipidemic and hepatoprotective activities. PVS-NEs were prepared using the aqueous titration method, where oleic acid was chosen as an oil phase, and span 80 and tween 80 were used as surfactant and cosurfactant respectively. Droplet size (DS), polydispersity index (PDI), zeta potential (ZP), clarity, and thermodynamic stability of NEs were all characterized. Also, PVS-NEs (NE2) with 50% oil phase, 40% SC mix 2:1, and 10% water were selected as an optimum formula based on the results of DS (251 ± 16), PDI (0.4 ± 0.16), and ZP (-70 ± 10.4) to be incorporated into a transdermal patch, and PVS-NE2 loaded transdermal patches (PVS-NE2-TDPs) were prepared by solvent evaporation method. F1 patch with HPMC E15 and PVP K30 in a ratio of 3:1 represented satisfactory patch properties with good drug-excipients compatibility. Thus, it was selected as an optimum patch formula. The optimized F1 patch was characterized for thickness, moisture content, weight variation, and drug-excipients incompatibility. Therefore, it was subjected to ex vivo skin permeation and finally pharmacodynamic studies. Ex vivo permeation studies of F1 revealed that the cumulative amount of PVS permeated across rat skin was 271.66 ± 19 µg/cm2 in 72 h, and the pharmacodynamic studies demonstrated that the F1 patch was more effective in treating hyperlipidemia than PVS-TDP (control patch) based on both blood analysis and histopathological examination. .


Assuntos
Hiperlipidemias , Pravastatina , Ratos , Animais , Administração Cutânea , Excipientes , Adesivo Transdérmico , Hiperlipidemias/tratamento farmacológico , Ratos Wistar
2.
Int J Nanomedicine ; 18: 721-742, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816332

RESUMO

Purpose: Pravastatin sodium (PVS) is a hypolipidemic drug which suffers from extensive first-pass metabolism and short half-life. Poly(d,l-lactide-co-glycolide) (PLGA) is considered a promising carrier to improve its hypolipidemic and hepatoprotective activities. Methods: PVS-loaded PLGA nanoparticles (PVS-PLGA-NPs) were prepared by double emulsion method using a full 32 factorial design. The in vitro release and the physical stability studies of the optimized PVS-PLGA-NPs (F5) were performed. Finally, both hypolipidemic and hepatoprotective activities of the optimized F5 NPs were studied and compared to PVS solution. Results: All the studied physical parameters of the prepared NPs were found in the accepted range. The particle size (PS) ranged from 90 ± 0.125 nm to 179.33 ± 4.509 nm, the poly dispersity index (PDI) ranged from 0.121 ± 0.018 to 0.158 ± 0.014. The optimized NPs (F5) have the highest entrapment efficiency (EE%) (51.7 ± 5%), reasonable PS (168.4 ± 2.506 nm) as well as reasonable zeta potential (ZP) (-28.3 ± 1.18mv). Solid-state characterization indicated that PVS is well entrapped into NPs. All NPs have distinct spherical shape with smooth surface. The prepared NPs showed a controlled release profile. F5 showed good stability at 4 ± 2°C during the whole storage period of 3 months. In vivo study and histopathological examination indicated that F5 NPs showed significant increase in PVS hypolipidemic as well as hepatoprotective activity compared to PVS solution. Conclusion: The PVS-PLGA-NPs could be considered a promising model to evade the first-pass effect and showed improvement in the hypolipidemic and hepatoprotective activities compared to PVS solution.


Assuntos
Ácido Láctico , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ácido Poliglicólico , Portadores de Fármacos/metabolismo , Pravastatina , Nanopartículas/metabolismo , Tamanho da Partícula
3.
Int J Nanomedicine ; 15: 1335-1347, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184589

RESUMO

BACKGROUND: Atorvastatin calcium (AT) is an ocular anti-inflammatory with limited bioavailability when taken orally due to its low solubility in low pH and extensive first-pass effect. To overcome these problems, AT was entrapped in polymeric nanoparticles (NPs) to improve surface properties and sustained release, in addition to achieving site-specific action. METHODS: AT was entrapped in chitosan (CS)-coated polylactic-co-glycolic acid (PLGA) NPs to form AT-PLGA-CS-NPs (F1). F1 and free AT were embedded in thermosensitive Pluronic®127-hydroxypropyl methylcellulose (HPMC) to form thermosensitive gels (F2) and (F3) while F4 is AT suspension in water. F1 was assessed for size, surface charge, polydispersity index (PDI), and morphology. F2 and F3 were examined for gelation temperature, gel strength, pH, and viscosity. In vitro release of the four formulations was also investigated. The ocular irritancy and anti-inflammatory efficacy of formulations against prostaglandin E1-(PGE1) induced ocular inflammation in rabbits were investigated by counting the polymorphonuclear leukocytes (PMNs) and protein migrated in tears. RESULTS: Oval F1 of 80.0-190.0±21.6 nm exhibited a PDI of 0.331 and zeta potential of 17.4±5.62 mV with a positive surface charge. F2 and F3 gelation temperatures were 35.17±0.22°C and 36.93±0.31°C, viscosity 12,243±0.64 and 9759±0.22 cP, gel strength 15.56±0.6 and 12.45±0.1 s, and pHs of 7.4±0.02 and 7.4±0.1, respectively. In vitro release of F1, F2, F3, and F4 were 48.21±0.31, 26.48±0.5, 84.76±0.11, and 100% after 24 hrs, respectively. All formulations were non-irritant. F2 significantly inhibited lid closure up to 3 h, PMN counts and proteins in tear fluids up to 5 h compared to other formulations. CONCLUSION: AT-PLGA-CS-NP thermosensitive gels proved to be successful ocular anti-inflammatory drug delivery systems.


Assuntos
Anti-Inflamatórios/farmacologia , Atorvastatina/farmacologia , Quitosana/química , Oftalmopatias/tratamento farmacológico , Inflamação/tratamento farmacológico , Nanopartículas/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Anti-Inflamatórios/administração & dosagem , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/farmacologia , Atorvastatina/administração & dosagem , Materiais Biocompatíveis/química , Disponibilidade Biológica , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Oftalmopatias/induzido quimicamente , Oftalmopatias/patologia , Géis/química , Inflamação/induzido quimicamente , Inflamação/patologia , Nanopartículas/química , Coelhos
4.
AAPS PharmSciTech ; 18(5): 1795-1809, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27830515

RESUMO

Econazole nitrate (EC) is an active, imidazole antifungal agent. However, low aqueous solubility and dissolution rate of EC has discouraged its usage for the treatment of ophthalmic fungal infection. In this study, inclusion complexes of EC with cyclodextrins were prepared to enhance its solubility, dissolution, and ocular bioavailability. To achieve this goal, EC was complexed with ß-CyD/HP-ß-CyD using kneading, co-precipitation, and freeze-drying techniques. Phase-solubility studies were performed to investigate the complexes in the liquid form. Additionally, the complexes in the solid form were characterized with Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and transmission electron microscopy (TEM). Furthermore, different eye drops containing EC-CyD complexes were prepared using different polymers and then characterized regarding their drug contents, pH, viscosity, mucoadhesive strength, and in vitro release characteristics. The results showed that stable EC-CyD complexes were formed in 1:1 molar ratio as designated by BS-type diagram. Econazole nitrate water solubility was significantly increased in about three- and fourfold for ß-CyD and HP-ß-CyD, respectively. The results showed that the prepared complexes were spherical in shape having an average particle diameter from 110 to 288.33 nm with entrapment efficiency ranging from 64.24 to 95.27%. DSC investigations showed the formation of real inclusion complexes obtained with co-precipitation technique. From the in vitro studies, all eye drops containing co-precipitate complexes exhibited higher release rate than that of other complexes and followed the diffusion-controlled mechanism. In vivo study proved that eye drops containing EC-CyD complexes showed higher ocular bioavailability than EC alone which indicated by higher AUC, Cmax, and relative bioavailability values.


Assuntos
Ciclodextrinas/administração & dosagem , Ciclodextrinas/química , Econazol/administração & dosagem , Econazol/química , Administração Oftálmica , Animais , Antifúngicos/administração & dosagem , Antifúngicos/química , Antifúngicos/metabolismo , Disponibilidade Biológica , Varredura Diferencial de Calorimetria/métodos , Ciclodextrinas/metabolismo , Econazol/metabolismo , Liofilização/métodos , Masculino , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos
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