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1.
Drug Deliv ; 29(1): 3304-3316, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36372978

RESUMO

Onychomycosis accounts for 90% of nail infections worldwide. Topical therapy provides localized effects with minimal adverse systemic actions, yet its effectiveness is limited by minimal drug permeation through the keratinized nail plate. Ciclopirox (CIX) is a FDA-approved broad-spectrum antimycotic agent. However, the complete cure with its nail lacquer (8% w/v) may continue for one year with a high cost. Therefore, poly lactide-co-glycolide (PLGA) nanocapsules (NCs) of CIX were prepared by nanoprecipitation and optimized through a 23 factorial design to be incorporated into hydroxypropyl chitosan (HPCH) based nail lacquer. Nail hydration, in vitro nail absorption, minimum inhibitory concentration (MIC), inhibition zones and ex vivo fungal growth on nail fragments were evaluated. The optimized NCs of CIX based on 100 mg PLGA 2 A and lipoid S75 showed a mean diameter of 174.77 ± 7.90 nm, entrapment efficiency (EE%) of 90.57 ± 0.98%, zeta potential (ZP) of -52.27 ± 0.40 mV and a prolonged drug release. Nail lacquer of the optimized NCs exhibited a higher stability than NCs dispersion. Compared to CIX solution (1% w/v), the respective decrease in MIC for NCs and their lacquer was four- and eight-fold. The lacquer superiority was confirmed by the enhancement in the nail hydration and absorption by 4 and 2.60 times, respectively, relative to CIX solution and the minimal ex vivo fungal growth. Therefore, HPCH nail lacquer of (1% w/v) CIX-PLGA-NCs can be represented as a potential topical delivery system for enhanced in vitro nail absorption and therapeutic efficacy against onychomycosis at a low dose.


Assuntos
Quitosana , Nanocápsulas , Onicomicose , Humanos , Onicomicose/tratamento farmacológico , Ciclopirox/uso terapêutico , Laca , Antifúngicos , Piridonas , Administração Tópica
2.
Drug Deliv ; 28(1): 1795-1809, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34470551

RESUMO

Nizatidine (NIZ), a histamine H2-receptor antagonist, is soluble and stable in the stomach, however, it exhibits a short half-life and a rapid clearance. Therefore, chitosan (CS) and polyethylene oxide (PEO) nanofibers (NFs) at different weight ratios were prepared by electrospinning and characterized. The selected uncrosslinked and glutaraldehyde-crosslinked NFs were investigated regarding floating, solid-state characteristics, in vitro release, and in vitro cytotoxicity. The cytoprotective activity against ethanol-induced gastric injury in rats was evaluated through macroscopical, histopathological, immunohistochemical, and oxidative stress examinations. NFs based on 8:2 CS:PEO exhibited the smallest diameter (119.17 ± 22.05 nm) and the greatest mucoadhesion (22.82 ± 3.21 g/cm2), so they were crosslinked with glutaraldehyde. Solid-state characterization indicated polymers interaction, a successful crosslinking, and NIZ dispersion in NFs. Crosslinking maintained swollen mats at pH 1.2 (swelling% = 29.47 ± 3.50% at 24 h), retarded their erosion at pH 6.8 (swelling%= 84.64 ± 4.91% vs. 25.40 ± 0.79% for the uncrosslinked NFs at 24 h), augmented the floating up to 24 h vs. 10 min for the uncrosslinked NFs at pH 1.2 and prolonged the drug release (%drug released ≥ 93% at 24 h vs. 4 and 5 h for the uncrosslinked NFs at pHs 1.2 and 6.8, respectively). The viability of Caco-2 cells ≥ 86.87 ± 6.86% revealed NFs biocompatibility and unreacted glutaraldehyde removal. Crosslinking of 8:2 CS:PEO NFs potentiated the antiulcer activity (38.98 vs. 8.67 for the uncrosslinked NFs) as well as it preserved the gastric wall architecture, COX-2 expression, and oxidative stress markers levels of the normal rats.


Assuntos
Antiulcerosos/farmacologia , Quitosana/química , Glutaral/química , Nanofibras/química , Nizatidina/farmacologia , Polietilenoglicóis/química , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacocinética , Células CACO-2 , Sobrevivência Celular , Química Farmacêutica , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Nizatidina/administração & dosagem , Nizatidina/farmacocinética , Distribuição Aleatória , Ratos
3.
Drug Des Devel Ther ; 14: 677-696, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32109993

RESUMO

BACKGROUND: Naringin is a promising anti-inflammatory drug against various disorders including ulcerative colitis. However, its oral bioavailability is low (8%) possibly due to cleavage at the upper gut. Consequently, colon targeting would be necessary for drug protection at the upper gut, enhanced oral bioavailability and potentiated cytoprotection against colitis. METHODOLOGY: This study involved the formulation of compression-coated tablets of naringin employing mixtures of pH-sensitive Eudragit L100-55 (EUD-L100-55) and different time-dependent polymers including ethyl cellulose (EC), sodium alginate (ALG) and sodium carboxymethyl cellulose (SCMC). Drug-polymer interaction during release was assessed using Fourier transform-infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Tablets were evaluated in vitro. Surface morphology of the optimized tablets either before or after exposure to the different release media was examined employing scanning electron microscopy (SEM). Cytoprotection potential of the optimized tablets against indomethacin-induced colitis in rabbits was screened and compared to core tablets through a histopathological examination of colon, measurement of serum perinuclear antineutrophil cytoplasmic antibodies (pANCA) and immunohistochemical localization of tumor necrosis factor-alpha (TNF-α). RESULTS: FT-IR and DSC results may indicate drug-polymers interaction during release. Release retardation could be related to polymer swelling that was in the order of SCMC > ALG > EC. SEM examination indicated more porous coats at the buffers relative to the acidic medium. Colon targeting was expected in case of coats of 5% ALG, 5% SCMC and 10% EC (w/w) in combination with EUD-L100-55; thus, they were selected for in vivo evaluation. Effective cytoprotection of selected tablets against indomethacin-induced colitis was indicated by a significant (P<0.05) reduction in mucosal damage, serum levels of pANCA and TNF-α expression compared to untreated colitis and core-pretreated groups. Compared to EC, higher cytoprotection potential of ALG- and SCMC-based tablets was reflected by lower concentration (5% w/w) to provide cytoprotection against indomethacin-induced colitis.


Assuntos
Anti-Inflamatórios/farmacologia , Colite Ulcerativa/tratamento farmacológico , Citoproteção/efeitos dos fármacos , Flavanonas/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Colite Ulcerativa/induzido quimicamente , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Flavanonas/administração & dosagem , Indometacina , Cinética , Masculino , Coelhos
4.
Int J Nanomedicine ; 14: 7191-7213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564873

RESUMO

BACKGROUND: Diosmin showed poor water solubility and low bioavailability. Poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles were successfully used to improve the drugs solubility and bioavailability. Coating of PLGA nanoparticles with chitosan can ameliorate their gastric retention and cellular uptake. METHODOLOGY: PLGA nanoparticles of diosmin were prepared using different drug and polymer amounts. Nanoparticles were selected based on entrapment efficiency% (EE%) and particle size measurements to be coated with chitosan. The selected nanoparticles either uncoated or coated were evaluated regarding morphology, ζ-potential, solid-state characterization, in vitro release, storage stability, and mucoadhesion. The anti-ulcer activity (AA) against ethanol-induced ulcer in rats was assessed through macroscopical evaluation, histopathological examination, immunohistochemical localization of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transmission electron microscopic examination of gastric tissues compared to free diosmin (100 mg/kg) and positive control. RESULTS: Based on EE% and particle size measurements, the selected nanoparticles, either uncoated or coated with 0.1% w/v chitosan, were based on 1:15 drug-PLGA weight ratio and 20 mg diosmin employing methylene chloride as an organic phase. Examination by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed nanoscopic spherical particles. Drug encapsulation within the selected nanoparticles was suggested by Fourier transform-infrared, differential scanning calorimetry (DSC) and X-ray diffractometry results. Chitosan-coated nanoparticles were more stable against size enlargement probably due to the higher ζ-potential. Only coated nanoparticles showed gastric retention as revealed by SEM examination of stomach and duodenum. The superior AA of coated nanoparticles was confirmed by significant reduction in average mucosal damage, the majority of histopathological changes and NF-κB expression in gastric tissue when compared to positive control, diosmin and uncoated nanoparticles as well as insignificant difference relative to normal control. Coated nanoparticles preserved the normal ultrastructure of the gastric mucosa as revealed by TEM examination. CONCLUSION: The optimized chitosan-coated PLGA nanoparticles can be represented as a potential oral drug delivery system of diosmin.


Assuntos
Antiulcerosos/uso terapêutico , Quitosana/química , Diosmina/uso terapêutico , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Estômago/patologia , Úlcera/tratamento farmacológico , Adesividade , Animais , Antiulcerosos/farmacologia , Varredura Diferencial de Calorimetria , Diosmina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Duodeno/efeitos dos fármacos , Duodeno/patologia , Duodeno/ultraestrutura , Mucosa Gástrica/patologia , Mucosa Gástrica/ultraestrutura , Cinética , Masculino , Muco/química , NF-kappa B/metabolismo , Nanopartículas/ultraestrutura , Tamanho da Partícula , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Estômago/efeitos dos fármacos , Estômago/ultraestrutura , Úlcera/patologia , Difração de Raios X
5.
Pharm Dev Technol ; 24(1): 48-62, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29210317

RESUMO

Fungal keratitis may cause vision loss if it is not treated. Methods other than ocular delivery exhibited several limitations. No previous studies investigated and compared ocular bioavailability of fluconazole (FLZ) from niosomal gels and microemulsions. Niosomal gels of FLZ (0.3% w/w) based on Span® 60 and cholesterol (CH) using 1% w/w carbopol® 934 (CP) were evaluated. FLZ microemulsions (0.3% w/v) containing isopropyl myristate (IPM, as oil phase) and a 3:1 mixture of Tween® 80 (as surfactant) and polyethylene glycol 400 (PEG 400, as cosurfactant) were characterized. Optimized formulations were compared for their ocular bioavailability in rabbit's. Nanoscopic niosomes (63.67-117.13 nm) and microemulsions (57.05-59.93 nm) showed respective negative zeta potential ranges of -45.37 to -61.40 and -20.50 to -31.90 mV and sustained release up to 12 h. Entrapment efficiency (EE%) of niosomes ranged from 56.48% to 70.67%. Niosomal gels were more sustainable than niosomes and microemulsions. The most stable niosomal gel based on Span® 60 and CH at a molar ratio of 5:5 and microemulsion containing 45% w/w IPM and 40% w/w of 3:1 Tween® 80-PEG 400 mixture significantly (p < 0.0001) enhanced FLZ ocular bioavailability compared with its solution. Niosomal gel showed higher bioavailability than microemulsion by ≈2-fold.


Assuntos
Antifúngicos/administração & dosagem , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos , Fluconazol/administração & dosagem , Administração Oftálmica , Animais , Antifúngicos/farmacocinética , Disponibilidade Biológica , Preparações de Ação Retardada , Portadores de Fármacos/química , Emulsões , Olho/metabolismo , Fluconazol/farmacocinética , Géis , Lipossomos , Masculino , Tamanho da Partícula , Coelhos , Tensoativos/química
6.
Int J Nanomedicine ; 13: 6585-6602, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425476

RESUMO

BACKGROUND: Effective treatment of osteoarthritis necessitates both symptomatic relief and hindrance of joint degeneration progression. Non-steroidal anti-inflammatory drugs permit symptomatic relief only and can cause mucosal injury in the gut. Before absorption, diacerein (Dcn) is converted into rhein that counteracts cartilage degeneration without affecting prostaglandin production. Yet, low solubility and laxative action of unabsorbed rhein in the colon hindered its use. Thus, enhanced Dcn dissolution would allow absorption at the upper gut improving its bioavailability and possibly abolishing the laxative action. METHODS: Therefore, self-nanoemulsifying drug delivery systems (SNEDDSs) with each of gelucire 44/14 (Glc) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) at different drug:carrier weight ratios of 1:1, 1:2, 1:4, 1:6, 1:8 and 1:10 were prepared by melt method and filled into hard gelatin capsules. The optimized binary systems were selected based on solid state characterization, scanning electron microscopy (SEM) and in vitro evaluation of the prepared SNEDDSs in comparison with their corresponding physical mixtures (PMs) and Dcn. The optimized systems were further examined with respect to their morphology, size distribution and ζ-potential. Moreover, the anti-inflammatory activity of the optimized systems against carrageenan-induced paw edema in rats was assessed through estimation of edema and edema inhibition percentages as well as histopathological examination and immunohistochemical localization of tumor necrosis factor-alpha (TNF-α) and caspase-3. RESULTS: Significantly (P<0.05) enhanced in vitro drug release was recorded for SNEDDSs with either carrier when compared to Dcn and the corresponding PMs. SNEDDSs based on 1:10 Dcn:Glc and 1:8 Dcn:TPGS showed significantly (P<0.05) reduced edema and inflammation as well as expression of TNF-α and caspase-3 relative to positive control and Dcn pretreated groups. CONCLUSION: These SNEDDSs can be represented as potential oral drug delivery systems of Dcn for enhanced dissolution and anti-inflammatory activity against carrageenan-induced paw edema.


Assuntos
Antraquinonas/farmacologia , Anti-Inflamatórios/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Nanopartículas/química , Administração Oral , Animais , Antraquinonas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Varredura Diferencial de Calorimetria , Carragenina , Caspase 3/metabolismo , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Cinética , Masculino , Nanopartículas/ultraestrutura , Tamanho da Partícula , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Fator de Necrose Tumoral alfa/metabolismo , Difração de Raios X
7.
Int J Nanomedicine ; 13: 1009-1027, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29497294

RESUMO

Naringin is one of the most interesting phytopharmaceuticals that has been widely investigated for various biological actions. Yet, its low water solubility, limited permeability, and suboptimal bioavailability limited its use. Therefore, in this study, polymeric micelles of naringin based on pluronic F68 (PF68) were developed, fully characterized, and optimized. The optimized formula was investigated regarding in vitro release, storage stability, and in vitro cytotoxicity vs different cell lines. Also, cytoprotection against ethanol-induced ulcer in rats and antitumor activity against Ehrlich ascites carcinoma in mice were investigated. Nanoscopic and nearly spherical 1:50 micelles with the mean diameter of 74.80±6.56 nm and narrow size distribution were obtained. These micelles showed the highest entrapment efficiency (EE%; 96.14±2.29). The micelles exhibited prolonged release up to 48 vs 10 h for free naringin. The stability of micelles was confirmed by insignificant changes in drug entrapment, particle size, and retention (%) (91.99±3.24). At lower dose than free naringin, effective cytoprotection of 1:50 micelles against ethanol-induced ulcer in rat model has been indicated by significant reduction in mucosal damage, gastric level of malondialdehyde, gastric expression of tumor necrosis factor-alpha, caspase-3, nuclear factor kappa-light-chain-enhancer of activated B cells, and interleukin-6 with the elevation of gastric reduced glutathione and superoxide dismutase when compared with the positive control group. As well, these micelles provoked pronounced antitumor activity assessed by potentiated in vitro cytotoxicity particularly against colorectal carcinoma cells and tumor growth inhibition when compared with free naringin. In conclusion, 1:50 naringin-PF68 micelles can be represented as a potential stable nanodrug delivery system with prolonged release and enhanced antiulcer as well as antitumor activities.


Assuntos
Antiulcerosos/farmacologia , Antineoplásicos/farmacologia , Portadores de Fármacos/química , Flavanonas/farmacologia , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Disponibilidade Biológica , Linhagem Celular Tumoral , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Feminino , Flavanonas/administração & dosagem , Flavanonas/química , Humanos , Masculino , Camundongos , Micelas , Tamanho da Partícula , Poloxâmero/química , Ratos Sprague-Dawley , Solubilidade , Úlcera/induzido quimicamente , Úlcera/tratamento farmacológico
8.
Eur J Pharm Sci ; 96: 232-242, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27667706

RESUMO

Vorinostat is the first histone deacetylase inhibitor approved by US FDA for use in cancer therapy. However, its limited aqueous solubility, low permeability, and suboptimal pharmacokinetics hinder its delivery. Thus, in this study, micelles of vorinostat with each of pluronic F68 (PF68) and pluronic F127 (PF127) were developed and optimized based on drug loading and entrapment. The optimized micelles were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), zeta analyzer, and electron transmission microscopy. Their in vitro release, stability, in vitro cytotoxicity against HepG2, Caco-2, and MCF-7 cell lines, and finally, in vivo antitumor activity in mice bearing Ehrlich Ascites Carcinoma (EAC) were assessed. The highest entrapment efficiency was 99.09±2.16% and 94.19±2.37% for micelles of 1:50 drug to polymer ratio with each of PF127 and PF68, respectively. These micelles were nearly spherical with nanoscopic mean diameters of 72.61±10.66nm for PF68 and 91.88±10.70nm for PF127 with narrow size distribution. The micelles provided prolonged release at phosphate buffer saline pH7.4 up to 24h for PF68 and 72h for PF127. Potentiation of in vitro cytotoxicity of vorinostat was more pronounced with PF127 micelles particularly against MCF-7 cells. Compared with free vorinostat, the micelles with PF127 were more effective in inhibiting tumor growth as well as exhibiting significantly (p<0.05) diminished hepatic and renal toxicities. In conclusion, 1:50 vorinostat-PF127 micelles may facilitate i.v. formulations and can be suggested as a promising stable and safe nanoparticulate delivery system with prolonged release and potentiated cytotoxicity.


Assuntos
Antineoplásicos/administração & dosagem , Citotoxinas/administração & dosagem , Portadores de Fármacos/administração & dosagem , Ácidos Hidroxâmicos/administração & dosagem , Micelas , Poloxâmero/administração & dosagem , Animais , Antineoplásicos/toxicidade , Células CACO-2 , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Citotoxinas/toxicidade , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/toxicidade , Portadores de Fármacos/toxicidade , Feminino , Células Hep G2 , Humanos , Ácidos Hidroxâmicos/toxicidade , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Células MCF-7 , Camundongos , Poloxâmero/toxicidade , Vorinostat
9.
Chem Pharm Bull (Tokyo) ; 64(1): 42-51, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26726743

RESUMO

Carbopol (CP) is a biocompatible bioadhesive polymer used as a matrix for gastroretentive (GR) tablets, however, its rapid hydration shortens its bioadhesion and floating when incorporated in effervescent formulae. The interpolymer complexation of CP with polyvinylpyrrolidone (PVP) significantly reduced the excessive hydration of CP, prolonging floating and maintaining the mucoadhesiveness. In early attempts, a lengthy process was followed to prepare such an interpolymer complex. In this study, an in situ interpolymer complexation between CP and two grades of PVP (K25 and K90) in 0.1 N HCl was investigated and characterized by Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Hence, directly compressed GR tablets of different combinations of PVP and CP with sodium bicarbonate (SB) as an effervescent agent were examined for prolonged gastroretention and sustained release of ranitidine hydrochloride (RHCl) as a model drug. Tablets were evaluated for in vitro buoyancy, bioadhesiveness, swelling, and drug release in 0.1 N HCl. All GR tablets containing PVP-CP combinations achieved more prolonged floating (>24 h) than CP tablets (5.2 h). Their bioadhesiveness, swelling, and drug release were dependent on the PVP molecular weight and its ratio to CP. Drug release profiles of all formulae followed non-Fickian diffusion. Formula containing the PVP K90-CP combination at a respective ratio of 1 : 3 (P90C13) was a promising system, exhibiting good floating and bioadhesive properties as well as sustained drug release. Abdominal X-ray imaging of P90C13 formula, loaded with barium sulfate, in six healthy volunteers showed a mean gastric retention period of 6.8±0.3 h.


Assuntos
Resinas Acrílicas/química , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacocinética , Povidona/química , Ranitidina/administração & dosagem , Ranitidina/farmacocinética , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/farmacocinética , Adulto , Antiulcerosos/química , Liberação Controlada de Fármacos , Absorção Gastrointestinal , Voluntários Saudáveis , Humanos , Cinética , Masculino , Povidona/administração & dosagem , Povidona/farmacocinética , Ranitidina/química , Bicarbonato de Sódio/administração & dosagem , Bicarbonato de Sódio/química , Bicarbonato de Sódio/farmacocinética , Comprimidos , Adulto Jovem
10.
AAPS PharmSciTech ; 17(2): 328-38, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26092303

RESUMO

Currently available anti-ulcer drugs suffer from serious side effects which limited their uses and prompted the need to search for a safe and efficient new anti-ulcer agent. Boswellia gum resin (BR) emerged as a safe, efficient, natural, and economic potential cytoprotective agent. Thus, it is of medical importance to develop gastroretentive (GR) formulations of BR to enhance its bioavailability and anti-ulcer efficacy. Early attempts involved the use of organic solvents and non-applicability to large-scale production. In this study, different tablet formulations were prepared by simple direct compression combining floating and bioadhesion mechanisms employing hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (SCMC), pectin (PC), and/or carbopol (CP) as bioadhesive polymers and sodium bicarbonate (SB) as a gas former. The prepared tablets were subjected for assessment of swelling, floating, bioadhesion, and drug release in 0.1 N HCl. The optimized GR formulation was examined for its protective effect on the gastric ulcer induced by indomethacin in albino rabbits compared with lactose tablets. The obtained results disclosed that swelling, floating, bioadhesion, and drug release of the GR tablets of BR depend mainly on the nature of the matrix and the ratio of polymer combinations. Moreover, a combination of SCMC-CP in a ratio of 2:1 (SCP21) exhibited desirable floating, bioadhesion, swelling, and extended drug release. Also, a 6-h pretreatment with SCP21 tablets decreased the severity of inflammation and number of bleeding spots among ulcer-induced rabbits in comparison to those treated with lactose tablets.


Assuntos
Boswellia/química , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Resinas Vegetais/química , Úlcera Gástrica/tratamento farmacológico , Comprimidos/química , Comprimidos/farmacologia , Resinas Acrílicas/química , Animais , Antiulcerosos/química , Antiulcerosos/farmacocinética , Antiulcerosos/farmacologia , Disponibilidade Biológica , Carboximetilcelulose Sódica/química , Química Farmacêutica/métodos , Liberação Controlada de Fármacos , Excipientes/química , Derivados da Hipromelose/química , Indometacina/farmacologia , Masculino , Pectinas/química , Polímeros/química , Substâncias Protetoras/farmacocinética , Coelhos , Bicarbonato de Sódio/química , Úlcera Gástrica/induzido quimicamente , Comprimidos/farmacocinética
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