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1.
AAPS PharmSciTech ; 22(5): 181, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34129154

RESUMO

In this study, two hydrophilic polymers hydroxypropyl methyl cellulose and beta-cyclodextrin (ß-CD) are used to synthesize highly responsive and spongy polymeric matrices. Porous and stimulus-responsive polymeric network was developed to improve the solubility of acyclovir (ACV) at significant level. Grafting was successfully carried out by free radical polymerization technique. Spongy matrices were characterized by percentage entrapment efficiency, drug loading, solubility studies, FTIR, powder X-ray diffraction, TGA, DSC, XRD, SEM, swelling studies, and in vitro studies. Acute oral toxicity studies were conducted to determine the safety of oral administration of prepared HPMC-ßCD-g-poly(AMPS) formulation. Porous and spongy structures were depicted in SEM images. Complex formation and thermal stability of constituents and drug (ACV) were analyzed by FTIR, TGA, and DSC spectra. XRD analysis revealed reduction in acyclovir crystallinity in spongy matrices. Particle size of optimized formulation was found in the range of 197 ± 2.55 nm. The momentous difference with reference product committed that drug solubility and release characteristics were markedly enhanced by the developed spongy matrices. Toxicity studies endorsed that developed spongy matrices were non-toxic and compatible to biological system. The efficient method of preparation, enhanced solubility, excellent physico-chemical characteristics, high dissolution, and non-toxic HPMC-ßCD-g-poly(AMPS) spongy matrices may be a promising approach for oral delivery of poorly soluble drugs.


Assuntos
Acrilamidas/síntese química , Aciclovir/síntese química , Alcanossulfonatos/síntese química , Derivados da Hipromelose/síntese química , Polimerização , beta-Ciclodextrinas/síntese química , Acrilamidas/administração & dosagem , Aciclovir/administração & dosagem , Administração Oral , Alcanossulfonatos/administração & dosagem , Animais , Antivirais/administração & dosagem , Antivirais/síntese química , Avaliação Pré-Clínica de Medicamentos/métodos , Derivados da Hipromelose/administração & dosagem , Masculino , Tamanho da Partícula , Polímeros/administração & dosagem , Polímeros/síntese química , Coelhos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos , beta-Ciclodextrinas/administração & dosagem
2.
Retina ; 40(8): 1616-1622, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31490296

RESUMO

PURPOSE: This study examines the impact of corneal surface lubricants used during pars plana vitrectomy on corneal edema. METHODS: This prospective, observational, clinical study occurred at an academic institution. Participants were individuals aged 18 years and older who had already consented to undergo pars plana vitrectomy, without pre-existing corneal pathology. A corneal lubricant was chosen by the surgeon. Corneal thickness was measured preoperatively and postoperatively using pachymetry and anterior segment optical coherence tomography (AS-OCT). Main outcome measure was change in corneal thickness as measured by pachymetry. RESULTS: Forty-one patients completed the study protocol. The 23 subjects in the SHCS group had a significantly smaller increase in corneal thickness as measured by pachymetry compared with the 18 subjects in the HPMC group (29.9 µm vs. 58.1 µm, P value 0.02). When measured by anterior segment optical coherence tomography, the SHCS group had a smaller increase in corneal thickness compared with the HPMC group (0.04 mm vs. 0.06 mm, P value 0.09) but did not reach significance. CONCLUSION: SHCS is associated with reduced postoperative increase in corneal pachymetry as compared to HPMC.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Córnea/patologia , Ácido Hialurônico/administração & dosagem , Derivados da Hipromelose/administração & dosagem , Descolamento Retiniano/cirurgia , Perfurações Retinianas/cirurgia , Vitrectomia , Hemorragia Vítrea/cirurgia , Idoso , Córnea/diagnóstico por imagem , Paquimetria Corneana , Combinação de Medicamentos , Feminino , Humanos , Lubrificantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência Óptica
3.
Dysphagia ; 35(2): 231-241, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31073746

RESUMO

Dysphagia is a significant late morbidity following treatment with radiotherapy (RT) for head and neck squamous cell carcinomas (HNSCC). The purpose of this feasibility study was to test a gel-based saliva substitute to reduce the subjective assessment of dysphagia while eating food items varying in size and texture. Eligible study subjects treated with curative intended RT and suffering from dysphagia and xerostomia were recruited from the outpatient clinic during a two-month period. Nineteen subjects consented to participation and completed the EORTC QLQ-H&N35 questionnaire and three test meals. A Numeric Rating Scale (NRS) was used for subjective assessment of dysphagia during all test meals. All data on patient, tumor, and treatment characteristics were obtained from the Danish Head and Neck Cancer (DAHANCA) database. NRS data suggested reduction of dysphagia after application of the oral gel. The swallowing dysfunctions, discomfort while swallowing (p = 0.008), stuck food items (p = 0.02), and multiple attempts of clearing the throat (p = 0.05), improved significantly for soft and regular items. Both small- and large-sized food items were tested. EORTC QLQ-H&N35 showed improvement regarding eating problems (p = 0.03) and social eating (p = 0.02). No episodes of food aspiration were recorded during the test meals. Late dysphagia reduces QOL and is an important morbidity following RT. In this feasibility study, the oral gel was able to reduce dysphagia while eating soft and selected regular food items. Eating-related EORTC QLQ-H&N35 items also improved, indicating a beneficial reduction in dysphagia after application of the oral gel.


Assuntos
Transtornos de Deglutição/tratamento farmacológico , Derivados da Hipromelose/administração & dosagem , Lubrificantes/administração & dosagem , Lesões por Radiação/tratamento farmacológico , Xerostomia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Sobreviventes de Câncer , Transtornos de Deglutição/etiologia , Estudos de Viabilidade , Feminino , Géis , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Lesões por Radiação/etiologia , Saliva , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Resultado do Tratamento , Xerostomia/etiologia
4.
AAPS PharmSciTech ; 20(2): 68, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30627938

RESUMO

In the present contribution, the aim is to explore and establish a way in which 3D printing and gastro-retentive drug delivery systems (GRDDSs) are combined (focusing on inner structure innovation) to achieve extended and stable gastro-retention and controlled-release of drug. Three digital models diverse in construction were designed and substantialized by a pressure-assisted microsyringe (PAM) 3D printer. Preparations were characterized by means of DSC, XRD, FTIR, and SEM. In vitro buoyancy study and in vivo gamma scintigraphy method were conducted to validate gastro-retention property of these innovative preparations in vitro/in vivo respectively. Release kinetic model was established and release mechanism was discussed. Tablets manufactured under certain range of parameters (intersecting angle, full filling gap) were tight and accurate in shape. Tablets printed with specific parameters (full filling gap, 50%; nozzle extrusion speed, 0.006 mm/s; layer height, 0.4 mm; compensation value, 0.25; quantity of layers, 15; outline printing value, 2) exhibited satisfactory in vitro (10-12 h)/in vivo (8-10 h) retention ability and possessed stable 10-12 h controlled-release quality. In general, 3D printing has tremendous advantage over conventional fabrication technique in intricate drug delivery systems and will be widely employed in pharmacy.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Derivados da Hipromelose/administração & dosagem , Impressão Tridimensional , Estômago/efeitos dos fármacos , Estômago/diagnóstico por imagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Ginkgo biloba , Humanos , Derivados da Hipromelose/química , Derivados da Hipromelose/metabolismo , Comprimidos/química , Tecnologia Farmacêutica/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos
5.
AAPS PharmSciTech ; 20(5): 210, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161269

RESUMO

Dorzolamide HCl (DRZ) ophthalmic drop is one of the most common glaucoma medications which rapidly eliminates after instillation leading to short residence time of the drug on cornea. The purpose of the present study is to develop a pH-triggered in situ gel system for ophthalmic delivery of DRZ for treatment of ocular hypertension. In this study, a 32 full factorial design was used for preparation of in situ gel formulations using different levels of Carbopol® and hydroxyl propyl methyl cellulose (HPMC). Rheological behavior, in vitro drug release, ex vivo corneal permeability, and IOP-lowering activity were investigated. DRZ solution (2% w/v) containing of 0.1% (w/v) Carbopol® and 0.1% (w/v) HPMC was selected as the optimal formulation considering its free flow under non-physiological conditions (initial pH and 25 ± 2°C) and transition to appropriate gel form under physiological circumstance (pH 7.4 and 34°C). This in situ gel presented the mucoadhesive property. Ex vivo corneal permeability of this combined solution was similar to those of DRZ solution. The developed formulation compared to the marketed drop (Biosopt®) and DRZ 2% solution had a better performance in intraocular pressure activity. The efficiency and long duration of IOP reduction could be due to the prolonged residence time of the in situ gel. The presence of Carbopol® as a pH triggered and mucoadhesive polymer causes to attach to the ocular mucosal surface for a long term.


Assuntos
Resinas Acrílicas/farmacocinética , Anti-Hipertensivos/farmacocinética , Portadores de Fármacos/farmacocinética , Derivados da Hipromelose/farmacocinética , Sulfonamidas/farmacocinética , Tiofenos/farmacocinética , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/síntese química , Administração Oftálmica , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/síntese química , Córnea/efeitos dos fármacos , Córnea/metabolismo , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Avaliação Pré-Clínica de Medicamentos/métodos , Liberação Controlada de Fármacos , Géis , Glaucoma/tratamento farmacológico , Glaucoma/metabolismo , Concentração de Íons de Hidrogênio , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/síntese química , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Masculino , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/síntese química , Soluções Oftálmicas/farmacocinética , Coelhos , Sulfonamidas/administração & dosagem , Sulfonamidas/síntese química , Suínos , Tiofenos/administração & dosagem , Tiofenos/síntese química
6.
AAPS PharmSciTech ; 19(4): 1520-1528, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29464592

RESUMO

An account is given of the recent development of the highly viscous complex biopharmaceuticals in relation to syringeability and injectability. The specific objective of this study is to establish a convenient method to examine problem of the injectability for the needle-syringe-formulation system when complex formulations with diverse viscosities are used. This work presents the inter-relationship between needle size, syringe volume, viscosity, and injectability of polymeric solutions having typical viscosities encountered in concentrated biologics, by applying a constant probe crosshead speed on the plunger-syringe needle assembly and continuously recording the force-distance profiles. A computerized texture analyzer was used to accurately capture, display, and store force, displacement, and time data. The force-distance curve and area under the curve are determined, and total work done for complete extrusion of the syringe content was calculated automatically by applying an established Matlab program. Various concentrations (i.e., 0.5-4% w/v of polymeric fluids/dispersions) of polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) with viscosity ranges of 5-100 cP mimicking concentrated monoclonal antibody solutions and complex biopharmaceutical formulations are investigated. Results indicate that calculated values of total work done to completely extrude the syringe content are the most appropriate parameter that describes viscosity-injection force of dispersed formulations. Additionally, the rheological properties of HPMC and PEO fluids in the context of syringeability and injectability are discussed.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Polímeros/administração & dosagem , Polímeros/química , Seringas , Biofarmácia/instrumentação , Biofarmácia/métodos , Sistemas de Liberação de Medicamentos/instrumentação , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/química , Injeções , Fenômenos Mecânicos , Metilcelulose/administração & dosagem , Metilcelulose/química , Reologia , Viscosidade
7.
AAPS PharmSciTech ; 19(5): 2203-2212, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29728997

RESUMO

This work aimed to using optimization study to formulate a patient-friendly captopril fast-dissolving oral film with satisfactory disintegration time. Films were made with pullulan and hydroxypropyl methyl cellulose (HPMC) by using the solvent-casting method. Cellulose nanofiber (CNF) was used as a compatibilizer and glycerine was used as a plasticizer. In order to find an optimum formulation, a response surface methodology and a central composite design were employed. The concentration percentages of pullulan and glycerine were considered to be the design factors. Disintegration time, tensile strength, percent elongation at break, and folding endurance were considered to be the responses. The results showed that CNF improved the compatibility and tensile strength of the pullulan and HPMC blend. Also, the rigid nature of CNF reduced the film elongation but the addition of glycerine improved its flexibility. All formulations showed an acceptable uniformity content and dissolution rate. Complete dissolution for all formulations occurred within 2 min. Films with 26% pullulan, 74% HPMC, 1% CNF, and 5% glycerine were reported to be optimum formulations for captopril fast-dissolving oral films, with 95% confidence levels. The in vivo comparison of optimized formulation with a conventional captopril sublingual tablet exhibited significant increase in AUC (~ 62%) and Cmax (~ 52%) and a major decrease in Tmax (~ 33%). The overall results showed that the captopril FDF is a promising candidate for enhanced in vivo orotransmucosal absorption.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/síntese química , Captopril/administração & dosagem , Captopril/síntese química , Composição de Medicamentos/métodos , Administração Oral , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Captopril/metabolismo , Glucanos/administração & dosagem , Glucanos/síntese química , Glucanos/metabolismo , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/síntese química , Derivados da Hipromelose/metabolismo , Nanofibras/administração & dosagem , Nanofibras/química , Coelhos , Distribuição Aleatória , Solubilidade , Resistência à Tração
8.
AAPS PharmSciTech ; 19(3): 1392-1400, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29396734

RESUMO

Iloperidone is a second-generation antipsychotic drug which is used for the treatment of schizophrenia and has very low aqueous solubility and bioavailability. This drug also undergoes first-pass metabolism. The aim of this work is to formulate fast-dissolving sublingual films of iloperidone to improve its bioavailability. Sublingual films were prepared by solvent casting method. Hydroxypropyl methyl cellulose E5, propylene glycol 400, and transcutol HP were optimized using Box-Behnken three-level statistical design on the basis of disintegration time and folding endurance of films. Iloperidone:hydroxypropyl-ß-cyclodextrin kneaded complex was used in films instead of plain drug due to its low solubility. Optimized film was further evaluated for drug content, pH, dissolution studies, ex vivo permeation studies, and pharmacokinetic studies in rats. The optimized film disintegrated within 30 s. The in vitro dissolution of the film showed 80.3 ± 3.4% drug dissolved within first 5 min. In ex vivo permeation studies using sublingual tissue, flux achieved within first 15 min by film was around 117.1 ± 0.35 (mcg/cm2/h) which was ten times more than that of plain drug. This formulation showed excellent uniformity. AUC and Cmax of film were significantly higher (p < 0.001) as compared to plain drug and relative bioavailability of the films was 148% when compared to the plain drug. Thus, this study showed optimized fast-dissolving sublingual film to improve permeation and bioavailability of iloperidone. Fast-dissolving films will be customer-friendly approach for geadiatric schizophrenic patients.


Assuntos
Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Composição de Medicamentos/métodos , Isoxazóis/química , Isoxazóis/metabolismo , Piperidinas/química , Piperidinas/metabolismo , Administração Oral , Administração Sublingual , Animais , Antipsicóticos/administração & dosagem , Antipsicóticos/química , Antipsicóticos/metabolismo , Disponibilidade Biológica , Portadores de Fármacos/administração & dosagem , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/química , Derivados da Hipromelose/metabolismo , Isoxazóis/administração & dosagem , Masculino , Absorção pela Mucosa Oral/efeitos dos fármacos , Absorção pela Mucosa Oral/fisiologia , Piperidinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Solubilidade
9.
AAPS PharmSciTech ; 19(2): 934-940, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29079988

RESUMO

Here, the mesoporous silica (Sylysia 350) was selected as mesoporous material, hydroxypropyl methylcellulose (HPMC) was selected as crystallization inhibitor, and febuxostat (FBT) was selected as model drug, respectively. The FBT-Sylysia-HPMC nanomatrix (FBT@SHN) was prepared. The characteristics of FBT@SHN were investigated in vitro and in vivo. Our results indicated that the FBT in FBT@SHN was in amorphous form. The solubility and dissolution of FBT in FBT@SHN were significantly increased. The oral bioavailability of FBT in FBT@SHN was greatly improved 5.8-fold compared with that in FBT suspension. This nanomatrix could be used as a drug delivery platform for improving the oral bioavailability.


Assuntos
Febuxostat/química , Febuxostat/metabolismo , Nanoestruturas/química , Polímeros/química , Polímeros/metabolismo , Administração Oral , Animais , Disponibilidade Biológica , Cristalização , Sistemas de Liberação de Medicamentos/métodos , Febuxostat/administração & dosagem , Supressores da Gota/administração & dosagem , Supressores da Gota/química , Supressores da Gota/metabolismo , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/química , Derivados da Hipromelose/metabolismo , Masculino , Metilcelulose/química , Nanoestruturas/administração & dosagem , Polímeros/administração & dosagem , Ratos , Ratos Sprague-Dawley , Dióxido de Silício/administração & dosagem , Dióxido de Silício/química , Dióxido de Silício/metabolismo , Solubilidade
10.
Int Ophthalmol ; 38(3): 1261-1273, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28699061

RESUMO

PURPOSE: To assess the effect of hydroxypropyl methylcellulose (HPMC) 2% to prevent dry eye during phacoemulsification in senile and diabetic patients. METHODS: This prospective interventional case series comprised 60 eyes (44 patients) with age-related cataract scheduled for standardized phacoemulsification surgery. The patients were assigned to receive either balanced saline solution (BSS, 30 eyes) or HPMC 2% (30 eyes) during surgery. Preoperative and postoperative examinations (1, 3, 7 and 30 days) included measurements of automatic noninvasive tear film breakup time (NITBUT), fluorescein staining, Schirmer I test, tear meniscus height, depth and area and subjective symptoms. Intraoperative application frequency was also assessed. RESULTS: The mean age of patients was 68.7 ± 2.3 years. The application frequency of BSS during surgery was significantly reduced in HPMC group (P = 0.001). The incidence of dry eye syndrome (DES) was significantly reduced in HPMC group in both senile and diabetic patients. Scores of subjective symptoms were significantly higher in the BSS group in 1 day (P = 0.003) and 3 days (P = 0.043) postoperatively. The first and average NITBUT were significantly higher in HPMC group in 1 day and 3 days after surgery, respectively (P = 0.012 and P = 0.024, respectively). NITBUT values did not significantly change postoperatively in the HPMC group (P > 0.05), while they were significantly lower postoperatively in the BSS group. CONCLUSIONS: Application of HPMC 2% during phacoemulsification reduced the incidence of DES and improved patients' satisfaction in both senile and diabetic cataract patients. It was also effective in maintaining corneal hydration and was able to significantly reduce the application frequency intraoperatively.


Assuntos
Catarata/complicações , Diabetes Mellitus Tipo 2/complicações , Síndromes do Olho Seco/prevenção & controle , Epitélio Corneano/patologia , Derivados da Hipromelose/administração & dosagem , Cristalino/diagnóstico por imagem , Facoemulsificação/métodos , Idoso , Idoso de 80 Anos ou mais , Catarata/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Relação Dose-Resposta a Droga , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/etiologia , Feminino , Seguimentos , Humanos , Período Intraoperatório , Cristalino/cirurgia , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento , Ultrassonografia
11.
Pak J Pharm Sci ; 31(5): 1903-1910, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30150187

RESUMO

The current study was designed to evaluate mucoadhesive buccal tablet containing metronidazole (MTZ) for local action aided by Hydroxypropylmethylcellulose K4M (HPMC) and Carbopol 940® (CP) as mucoadhesive polymers with other ingredients like sodium starch glycolate (SSG), polyvinyl pyrollidone K30 (PVP) as disintegrant and binders respectively. Formulations (F1-F8) were prepared by direct compression method and characterized for different physicochemical parameters. Results showed that the average weight and friability were within USP limits. Maximum mucoadhesive time was observed for F2 (14 hr) containing moderate amount of HPMC and CP used in the study. Up most mucoadhesive strength value was observed with F3 containing highest amount of HPMC used. Results indicated that high amount of HPMC was linked with the moderate to higher mucoadhesive strength and time. Maximum swelling index was observed in F7 (191.3%). Only F1-F3 showed complete in vitro MTZ release within 3 hr. Formulations containing PVP released MTZ incompletely over time while SSG released earlier. Formulation F1 was considered best in terms of MTZ release (100.5%) with diffusion based Korsmeyer-Peppas release kinetics. Therefore, MTZ exhibiting best physicochemical characters in mucoadhesive buccal tablet was found in F1 containing HPMC and CP in amounts of 37.5 mg and 25 mg, respectively, for local action.


Assuntos
Anti-Infecciosos/química , Desenvolvimento de Medicamentos/métodos , Gengivite , Metronidazol/química , Mucosa Bucal , Periodontite , Adesividade , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/análise , Gengivite/tratamento farmacológico , Gengivite/microbiologia , Humanos , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/análise , Derivados da Hipromelose/química , Metronidazol/administração & dosagem , Metronidazol/análise , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/microbiologia , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Comprimidos
12.
Chem Pharm Bull (Tokyo) ; 65(2): 166-177, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27904030

RESUMO

Even though experimental designs are becoming popular especially for conventional dosage forms, limited studies have been performed to optimize formulations of orally disintegrating films (ODFs). This study aimed to evaluate sildenafil citrate-loaded ODFs for a controlled release with hydroxypropyl methylcellulose as a film-forming polymer. A factorial design was utilized for optimization with three control factors: ethanol ratio, plasticizer ratio, and the type of plasticizer. Tensile strength, disintegration time, water contact angle, and thickness were chosen as responses. For optimization, water contact angle, disintegration time, and thickness were minimized, while the tensile strength was maximized. Based on the conditions, optimal formulations were achieved for each type of plasticizer. Evaluation of desirability indicated that the response values were close to the target. When these optimal formulations were validated, the optimal solutions and target values were similar with small biases. The formulations were characterized using scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, surface pH, in vitro dissolution, and drug release simulation with a mathematical modeling. After the drug was homogenously dispersed throughout the film, the crystalline form of the drug provided strong hydrogen bonds between the drug and the film components. Moreover, it showed a controlled drug release profiles that were well matched with simulated results. This study suggests that the optimized films may present a better alternative to conventional tablets for the treatment of male erectile dysfunction.


Assuntos
Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/química , Modelos Químicos , Citrato de Sildenafila/administração & dosagem , Citrato de Sildenafila/química , Administração Oral , Química Farmacêutica , Plastificantes , Solubilidade , Resistência à Tração
13.
Drug Dev Ind Pharm ; 43(1): 171-176, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27593737

RESUMO

CONTEXT: Pirfenidone (PFD) has exhibited therapeutic potential in the treatment of cell proliferative disorders. The previously developed 0.5% water-based PFD eye drops by our team exhibited antiscarring effectiveness and ocular safety but with a limit of short half-life and poor bioavailability. OBJECTIVE: To increase bioavailability of the water-based PFD eye drops, we prepared a viscous solution by adding hydroxypropyl methylcellulose (HPMC, F4M), which acted as a viscosity-enhancer. Subsequently, we compared the HPMC-based PFD solution with the water-based PFD eye drops. MATERIALS AND METHODS: PFD solution with 1% HPMC (w/v) was prepared, and the viscosities at different shear rates were measured to investigate its rheology. PFD concentrations in the tear, aqueous humor, conjunctiva, cornea, and sclerae of New Zealand rabbits were detected at different time points with high-performance liquid chromatography (HPLC) following single instillation of the 0.5% PFD (w/v) water-based eye drops or HPMC-based solution. RESULTS: Compared with the 0.5% water-based PFD eye drops, the HPMC-based solution increased the PFD levels in tears and prolonged the residence time from 10 to more than 20 min (p < .01). Consequently, the concentrations of PFD in aqueous humor, conjunctiva, cornea, and sclera were elevated to varying degrees until 90 min after topical administration. CONCLUSIONS: The developed formulation possesses a same readily administration and simple preparation as the PFD eye drops; however, the HPMC-based solution exhibited the higher bioavailability.


Assuntos
Derivados da Hipromelose/síntese química , Soluções Oftálmicas/síntese química , Piridonas/síntese química , Administração Tópica , Animais , Humor Aquoso/efeitos dos fármacos , Humor Aquoso/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/farmacocinética , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/farmacocinética , Soluções Farmacêuticas/administração & dosagem , Soluções Farmacêuticas/síntese química , Soluções Farmacêuticas/farmacocinética , Piridonas/administração & dosagem , Piridonas/farmacocinética , Coelhos , Viscosidade
14.
Biol Pharm Bull ; 39(10): 1588-1595, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27725435

RESUMO

The aim of this study was to develop and to investigate a film of compound Calculus Bovis Sativus (CBS) and ornidazole film. A uniform mucoadhesive film was herein successfully obtained by a film-forming solusion containing insoluable drug. This film, as a valid adjunct for the treatment of oral mucosal ulcer, consisted of two main drugs (CBS, ornidazole) and three polymers (hydroxypropyl methyl cellulose, chitosan, poly(vinyl alcohol) (PVA)). The film was prepared with the film-forming suspension, using casting-solvent evaporation technique. The drug content, release behavior, swelling index and mucoadhesive properties of the film were detected. Then the effects of the prepared film on a glacial acetic acid-induced oral mucosal ulceration model of rabbits were evaluated. Moreover, the in vivo release of bilirubin and ornidazole in saliva were also detected in the oral mucosae of healthy volunteers. The films showed favorable in vitro drug release behaviors and swelling properties. Mucosal wounds in the animals were significantly relieved. With the films well tolerated, the salivary concentrations of ornidazole were maintained above the minimum inhibitory concentration against CBS for about 2 h. The compound CBS and ornidazole film functioned better than the film only containing CBS and ornidazole did. Therefore, it is a potentially efficient drug delivery system for the treatment of oral ulcers.


Assuntos
Sistemas de Liberação de Medicamentos , Cálculos Biliares/química , Úlceras Orais/tratamento farmacológico , Ornidazol/administração & dosagem , Ácido Acético , Adesividade , Adulto , Animais , Bovinos , Quitosana/administração & dosagem , Quitosana/química , Liberação Controlada de Fármacos , Humanos , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/química , Masculino , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Úlceras Orais/induzido quimicamente , Úlceras Orais/patologia , Ornidazol/química , Ornidazol/farmacocinética , Ornidazol/uso terapêutico , Álcool de Polivinil/administração & dosagem , Álcool de Polivinil/química , Coelhos , Saliva/metabolismo , Adulto Jovem
15.
Acta Pol Pharm ; 73(1): 183-96, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27008813

RESUMO

A super-absorbent hydrogel was developed by crosslinking of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and acrylic acid with hydroxypropyl methylcellulose (HPMC) for controlled release drug delivery of captopril, a well known antihypertensive drug. Acrylic acid and AMPS were polymerized and crosslinked with HPMC by free radical polymerization, a widely used chemical crosslinking method. N,N'-methylenebisacrylamide (MBA) and potassium persulfate (KPS) were added as cross-linker and initiator, respectively. The hydrogel formulation was loaded with captopril (as model drug). The concentration of captopril was monitored at 205 nm using UV spectrophotometer. Equilibrium swelling ratio was determined at pH 2, 4.5 and 7.4 to evaluate the pH responsiveness of the formed hydrogel. The super-absorbent hydrogels were evaluated by FTIR, SEM, XRD, and thermal analysis (DSC and TGA). The formation of new copolymeric network was determined by FTIR, XRD, TGA and DSC analysis. The hydrogel formulations with acrylic acid and AMPS ratio of 4: 1 and lower amounts of crosslinker had shown maximum swelling. Moreover, higher release rate of captopril was observed at pH 7.4 than at pH 2, because of more swelling capacity of copolymer with increasing pH of the aqueous medium. The present research work confirms the development of a stable hydrogel comprising of HPMC with acrylic acid and AMPS. The prepared hydrogels exhibited pH sensitive behav-ior. This superabsorbent composite prepared could be a successful drug carrier for treating hypertension.


Assuntos
Captopril/administração & dosagem , Derivados da Hipromelose/administração & dosagem , Polímeros/administração & dosagem , Ácidos Sulfônicos/administração & dosagem , Captopril/química , Preparações de Ação Retardada , Hidrogéis , Concentração de Íons de Hidrogênio , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
16.
Pak J Pharm Sci ; 28(5): 1619-24, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26408881

RESUMO

In order to introduce an easily applicable, removable, painless and long-term drug delivery system for non-insulin dependent diabetes mellitus (NIDDM), hydroxyl propyl methyl cellulose with polyvinyl alcohol (HPMC-PVA) blend patches of metormin HCl were evaluated in vitro and in vivo. A suitable patch of metformin 800 mg with HPMC-PVA blend were used, following a three cycle freeze-thaw technique. Drug release kinetic profiles were performed in both patch and swim bladder. Albino mice were artificially generated as NIDDM mice by alloxan insertion i.p and after then treated with the therapeutic patch. Blood glucose was estimated by commercially available glucose kit based on glucose oxidase method. Drug release parameters from the patch and swim bladder were typical non-Fickian diffusion and both have the same kinetic constant, revealing its possible diffusion through stratum corneum. Hypoglycemia was observed in treatment of normal mice with TDDS of metformin HCl within 4 hours i.e. 25 ± 2.13 mg/dl and within 16 hours in diabetic rats blood glucose level returned to normal level i.e. from 360 ± 3.3 mg/dl (NIDDM level) to 105 ± 2.5 mg/dl (Normal level). The TDS-patch has got the same kinetic simulation with that of swim-bladder, which might be a prediction for in vivo application. Here metformin was delivered to diabetic mice and has got significant anti-diabetic effect can be considered as a kind of patch for NIDDM just like wearing and taking off a hand watch because hypoglycaemia can be removed by just taking off the patch.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Derivados da Hipromelose/administração & dosagem , Metformina/administração & dosagem , Álcool de Polivinil/administração & dosagem , Administração Cutânea , Aloxano , Animais , Feminino , Masculino , Camundongos
17.
J Cosmet Laser Ther ; 16(4): 185-90, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24684547

RESUMO

Nasolabial folds are a sign of aging and increasing number of people want filler injections in their nasolabial folds to look younger. Various dermal fillers are used for the correction of nasolabial folds. Recently, a novel injectible filler, polymethylmethacrylate (PMMA) and cross-linked dextran in hydroxypropyl methylcellulose, was introduced for facial contouring. This study was designed as a six-month, prospective, single-blinded, and open-label study in two centers located in Korea. Nineteen Korean patients received the novel filler injections on both nasolabial folds. At Weeks 4, 12, and 24, the efficacy and safety of the dermal filler were evaluated by blinded-investigators using clinical photographs. The mean Wrinkle Severity Rating Scale revealed significant decrease after dermal filler injections at each study visit. The decreased Wrinkle Severity Rating Scale was maintained for 6 months (p < 0.0001). The Global Aesthetic Improvement score showed an improvement greater than 2 in 95% of the per-proto col population 24 weeks after the injections. All patients (100%) experienced an improvement of their nasolabial folds at Week 24. There were no complications related to the novel filler injection. The novel dermal filler, PMMA, and cross-linked dextran in hydroxylpropyl methylcellulose, can be another safe and effective treatment option in the treatment of nasolabial folds.


Assuntos
Materiais Biocompatíveis/administração & dosagem , Dextranos/administração & dosagem , Derivados da Hipromelose/administração & dosagem , Sulco Nasogeniano , Polimetil Metacrilato/administração & dosagem , Envelhecimento da Pele , Adulto , Materiais Biocompatíveis/efeitos adversos , Dextranos/efeitos adversos , Feminino , Humanos , Derivados da Hipromelose/efeitos adversos , Injeções Intradérmicas , Injeções Subcutâneas , Pessoa de Meia-Idade , Fotografação , Polimetil Metacrilato/efeitos adversos , Estudos Prospectivos , Ritidoplastia , Método Simples-Cego
18.
J Cosmet Laser Ther ; 16(4): 191-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24684519

RESUMO

A novel injectable filler of polymethylmethacrylate (PMMA) and cross-linked dextran in hydroxypropyl methylcellulose was introduced in the commercial filler market. For soft tissue augmentation, safety and biocompatibility should be evaluated and the stability at the implantation site should be assessed using histologic evaluation. In order to evaluate the biocompatibility of the novel soft tissue filler, PMMA and cross-linked dextran in hydroxypropyl methylcellulose was subdermally injected into the skin of Sprague-Dawley Rats. Histologic evaluation was performed at 13 weeks and 12 months after the injection. Inflammatory cell infiltration, neovascularization, and fibrosis were scored according to defined grading systems. The mean score of the histologic evaluation was 5.7 and 3.9 at 13 weeks and 12 months, respectively. At 12 months after injection, the PMMA and cross-linked dextran in hydroxypropyl methylcellulose appeared to be kept in place through fine fibrous capsules. The mixture of PMMA and cross-linked dextran in hydroxypropyl methylcellulose can be safely applied for soft tissue augmentation with longevity of greater than 12 months.


Assuntos
Materiais Biocompatíveis/efeitos adversos , Dextranos/efeitos adversos , Derivados da Hipromelose/efeitos adversos , Polimetil Metacrilato/efeitos adversos , Pele/patologia , Animais , Materiais Biocompatíveis/administração & dosagem , Dextranos/administração & dosagem , Fibrose , Derivados da Hipromelose/administração & dosagem , Contagem de Linfócitos , Macrófagos , Neovascularização Patológica/induzido quimicamente , Neutrófilos , Polimetil Metacrilato/administração & dosagem , Ratos , Ratos Sprague-Dawley , Pele/irrigação sanguínea , Pele/efeitos dos fármacos
19.
Yao Xue Xue Bao ; 48(5): 767-72, 2013 May.
Artigo em Zh | MEDLINE | ID: mdl-23888703

RESUMO

Hydroxypropyl methylcellulose (HPMC) propels self-emulsifying drug delivery systems (SEDDS) to achieve the supersaturated state in gastrointestinal tract, which possesses important significance to enhance oral absorption for poorly water-soluble drugs. This study investigated capacities and mechanisms of HPMC with different viscosities (K4M, K15M and K100M) to inhibit drug precipitation of SEDDS in the simulated gastrointestinal tract environment in vitro. The results showed that HPMC inhibited drug precipitation during the dispersion of SEDDS under gastric conditions by inhibiting the formation of crystal nucleus and the growth of crystals. HPMC had evident effects on the rate of SEDDS lipolysis and benefited the distribution of drug molecules across into the aqueous phase and the decrease of drug sediment. The mechanisms were related to the formed network of HPMC and its viscosities and molecular weight. These results offered a reference for selecting appropriate type of HPMC as the precipitation inhibitor of supersaturatable SEDDS.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Emulsificantes/química , Derivados da Hipromelose/farmacologia , Indometacina/administração & dosagem , Caprilatos/química , Precipitação Química/efeitos dos fármacos , Cristalização , Emulsões , Etilenoglicóis/química , Glicerídeos/química , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/química , Indometacina/química , Lipólise/efeitos dos fármacos , Peso Molecular , Polietilenoglicóis/química , Viscosidade
20.
Int J Mol Sci ; 13(3): 3738-3750, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22489179

RESUMO

The effect of dietary feeding of hydroxyethyl methylcellulose (HEMC) and hydroxypropyl methylcellulose (HPMC) on the glucose metabolism and antioxidative status in mice under high fat diet conditions was investigated. The mice were randomly divided and given experimental diets for six weeks: normal control (NC group), high fat (HF group), and high fat supplemented with either HEMC (HF+HEMC group) or HPMC (HF+HPMC group). At the end of the experimental period, the HF group exhibited markedly higher blood glucose and insulin levels as well as a higher erythrocyte lipid peroxidation rate relative to the control group. However, diet supplementation of HEMC and HPMC was found to counteract the high fat-induced hyperglycemia and oxidative stress via regulation of antioxidant and hepatic glucose-regulating enzyme activities. These findings illustrate that HEMC and HPMC were similarly effective in improving the glucose metabolism and antioxidant defense system in high fat-fed mice and they may be beneficial as functional biomaterials in the development of therapeutic agents against high fat dietinduced hyperglycemia and oxidative stress.


Assuntos
Antioxidantes/farmacologia , Hipoglicemiantes/farmacologia , Derivados da Hipromelose/farmacologia , Metilcelulose/análogos & derivados , Aumento de Peso/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Glicemia/efeitos dos fármacos , Dieta Hiperlipídica , Suplementos Nutricionais , Glucose/metabolismo , Glicogênio/sangue , Hipoglicemiantes/administração & dosagem , Derivados da Hipromelose/administração & dosagem , Insulina/sangue , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Metilcelulose/administração & dosagem , Metilcelulose/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos
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