Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 542
Filtrar
1.
Int J Nanomedicine ; 15: 735-747, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099362

RESUMO

Introduction: Gambogic acid (GA) is proved to have anti-tumor effects on gastric cancer. Due to poor solubility, non-specific biological distribution, toxicity to normal tissues and short half-life, it is hard to be applied into the clinic. To overcome these issues, we developed a thermosensitive and injectable hydrogel composed of hydroxypropyl cellulose, silk fibroin and glycerol, with short gelling time, good compatibility and sustained release, and demonstrated that the hydrogel packaged with gambogic acid nanoparticles (GA-NPs) and tumor-penetrating peptide iRGD could improve the anti-tumor activity. Methods: The Gelling time and micropore size of the hydrogels were regulated through different concentrations of glycerol. Controlled release characteristics of the hydrogels were evaluated with a real-time near-infrared fluorescence imaging system. Location of nanoparticles from different carriers was traced by confocal laser scanning microscopy. The in vivo antitumor activity of the hydrogels packaging GA-NPs and iRGD was evaluated by investigating tumor volume and tumor size. Results: The thermo-sensitive properties of hydrogels were characterized by 3-4 min, 37°C, when glycerol concentration was 20%. The hydrogels physically packaged with GA-NPs and iRGD showed higher fluorescence intensity than other groups. The in vivo study indicated that the co-administration of GA-NPs and iRGD by hydrogels had higher antitumor activity than the GA-loaded hydrogels and free GA combining with iRGD. Free GA group showed few antitumor effects. Compared with the control group, the body weight in other groups had no obvious change, and the count of leukocytes and hemoglobin was slightly decreased. Discussion: The hydrogel constructed iRGD and GA-NPs exerted an effective anti-tumor effect possibly due to retention effect, local administration and continuous sustained release of iRGD promoting the penetration of nanoparticles into a deep part of tumors. The delivery system showed little systemic toxicity and would provide a promising strategy to improve anti-gastric cancer efficacy.


Assuntos
Antineoplásicos/uso terapêutico , Hidrogéis/química , Nanopartículas/química , Oligopeptídeos/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Temperatura , Xantonas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Bombyx , Linhagem Celular Tumoral , Fibroínas/química , Glicerol/química , Humanos , Derivados da Hipromelose/química , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Porosidade , Neoplasias Gástricas/patologia , Distribuição Tecidual , Xantonas/farmacologia
2.
Drug Dev Ind Pharm ; 46(1): 146-158, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31894720

RESUMO

The aim of this research was to assess the effect of polymer blend and effervescent components on the floating and swelling behaviors of swellable gastro-floating formulation as well as the drug release through a compartmental modeling analysis. Swellable gastro-floating formulation of freely water-soluble drug, metformin HCl as a drug model, was formulated and developed using D-optimal design. Polymer combination between interpolymer complex (IPC) (poly-vinyl acetate-copolymer methacrylate) and hydroxy propyl methyl cellulose (HPMC), and effervescent components were studied and optimized in this work. Several factors affecting the drug release behavior were determined e.g. swelling behavior, erosion behavior, and floating behavior were studied as well as the drug release through compartmental modeling analysis. The results revealed that the hydrophilic polymer was responsible for gas entrapment formed from effervescent reaction, meanwhile IPC contributed on maintaining the swollen matrix integrity through intermolecular polymer interaction. In addition, effervescent components played fundamental role in the formation of porous system as well as inducing burst release effect. Compartmental modeling provided different outlook about the drug release. Presence of IPC at a high proportion (10-15%) of the polymer blend modulated the changes of pattern of the drug release kinetics and mechanism. Finally, compartmental modeling-based approach was more adequate to describe the drug release kinetics and mechanism compared to the monophasic equation model correlating with process understanding of the drug release from swellable gastro-floating formulation.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Metacrilatos/química , Polímeros/química , Estômago/fisiologia , Administração Oral , Liberação Controlada de Fármacos , Derivados da Hipromelose/química , Derivados da Hipromelose/farmacologia , Cinética , Metacrilatos/farmacologia , Comprimidos
3.
Food Chem ; 309: 125579, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31683149

RESUMO

The development of functional foods requires a detailed understanding of the behavior of lipophilic protein (LP) in the presence of emulsion stabilizers at different pH conditions. In this study, we examined the interaction between hydroxypropyl methylcellulose (hypromellose, HPMC) and soybean lipophilic protein. To that end, we examined the stabilities of LP-HPMC emulsions at pH 3, 5, and 7, as well as the oil-release behavior of LP-HPMC emulsions during digestion. Fluorescence data showed that HPMC binds to LP with quenching at a single binding site that did not change with pH. Atomic-force microscopy, emulsification, and oxidation-stability analyses showed that HPMC improves the pH stability of the LP-HPMC emulsions, while simulated in-vitro digestion experiments showed that added HPMC delayed the release of lipids to varying degrees. The results of this study will aid in the development of emulsion-based functional foods, pharmaceutical carriers with controlled-release or sustained-release functional ingredients.


Assuntos
Derivados da Hipromelose/química , Proteínas de Soja/química , Emulsões/química , Concentração de Íons de Hidrogênio
4.
Eur J Pharm Sci ; 141: 105115, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31654755

RESUMO

In this study, we present the development of spray-dried pectin/hypromellose microspheres as efficient melatonin carrier for targeted nasal delivery. Different pectin to hypromellose weight ratios in the spray-dried feed were employed (i.e. 1:0, 3:1, 1:1 and 1:3) in order to optimise microsphere physicochemical properties influencing overall powder behaviour prior, during and upon nasal delivery. All microspheres assured complete melatonin entrapment and increased dissolution rate in relation to pure melatonin powder. Among all combinations tested, combining pectin with hypromellose at 1:3 wt ratio resulted in the microspheres with the highest potential for melatonin nasal delivery as they assured highest swelling ability and most prominent mucoadhesive properties. Studies on deposition profile revealed adequate turbinate and olfactory deposition of microsphere/lactose monohydrate powder blend administered nasally using MIAT® device, complementing findings relevant for their therapeutic potential. In conclusion, developed microspheres bear the potential to ensure prolonged melatonin retention at the nasal mucosa, improved bioavailability and advanced therapeutic outcome.


Assuntos
Derivados da Hipromelose , Melatonina , Microesferas , Mucosa Nasal/metabolismo , Pectinas , Adesividade , Administração Intranasal , Liberação Controlada de Fármacos , Derivados da Hipromelose/administração & dosagem , Derivados da Hipromelose/química , Melatonina/administração & dosagem , Melatonina/química , Modelos Biológicos , Mucosa Nasal/química , Pectinas/administração & dosagem , Pectinas/química
5.
Anticancer Res ; 39(12): 6531-6536, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810918

RESUMO

BACKGROUND/AIM: Oral mucositis is a significant side effect in cancer treatment. In this study, we aimed to develop a rebamipide-containing film using chitosan and hydroxypropyl methylcellulose (HPMC) to efficiently treat oral mucositis. MATERIALS AND METHODS: A 0.1% (w/v) rebamipide aqueous solution, a 1.4% (w/v) chitosan aqueous solution containing Pluronic® F-127, and a 1.0% (w/v) HPMC aqueous solution were mixed and dried using a square silicon frame to form a film. Cumulative release ratios of rebamipide from sample films were measured in a phosphate buffer (pH 6.8) at 37°C. RESULTS: Chitosan suppressed the release of rebamipide from the film for up to 30 min. HPMC contributed to the sustained release of the film over a relatively long period of time and the maintenance of its shape. CONCLUSION: The combined use of chitosan and HPMC is suitable as a base material for rebamipide-containing films.


Assuntos
Alanina/análogos & derivados , Quitosana/química , Derivados da Hipromelose/química , Quinolonas/química , Estomatite/induzido quimicamente , Alanina/química , Antineoplásicos/efeitos adversos , Preparações de Ação Retardada , Humanos , Estomatite/tratamento farmacológico
6.
AAPS PharmSciTech ; 21(1): 25, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848807

RESUMO

Alpha-arbutin is one of the most efficient skin lightener agents, which shows the effect on reducing the pigmentation by competitively inhibiting human tyrosinase. However, alpha-arbutin has difficulty in skin permeability due to its hydrophilic property. The objective of this study was, therefore, to develop alpha-arbutin-loaded dissolving microneedles (DMNs) for improving the delivery of alpha-arbutin into the skin. The DMN patch was prepared using Gantrez™ S-97, hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone K-90 (PVP), chitosan, and their combinations. The optimal 8% alpha-arbutin-loaded DMNs, aside from Gantrez™ S-97, was successfully formulated with combination of 8% w/w HPMC and 40% w/w PVP K-90 (HPMC/PVP) at the weight ratio of 1:1. Both DMNs had 100% of penetration into porcine skin. Over 12 h of skin permeation, the flux of Gantrez™ S-97 DMNs and the HPMC/PVP DMNs were 66.21 µg/cm2/h and 74.24 µg/cm2/h, respectively. The accumulation amount of alpha-arbutin in the skin from Gantrez™ S-97 DMNs and HPMC/PVP DMNs was 107.76 µg and 312.23 µg, respectively. In comparison to the gel formulations, Gantrez™ S-97 DMNs and HPMC/PVP DMNs increase the delivery of alpha-arbutin across the skin approximately 2 and 4.7 times, respectively. In vivo studies found that alpha-arbutin-loaded HPMC/PVP DMNs delivered more alpha-arbutin into the skin than commercial cream. Moreover, the skin can reseal naturally after removal of DMNs patch without any signs of infection and remain stable in accelerated conditions for 4 weeks. Accordingly, alpha-arbutin-loaded HPMC/PVP DMNs could be a promising delivery platform for promoting trans-epidermal delivery of alpha-arbutin for skin lightening.


Assuntos
Arbutina/administração & dosagem , Epiderme/metabolismo , Derivados da Hipromelose/química , Agulhas , Povidona/química , Pele/metabolismo , Administração Cutânea , Animais , Sistemas de Liberação de Medicamentos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Microinjeções , Suínos
7.
Int J Pharm ; 570: 118667, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31494238

RESUMO

Diabetic patients suffer from impaired wound healing. In this study, the anti-diabetic drug, Pioglitazone hydrochloride (PG), was loaded in three-dimensional (3D) composite scaffolds (SC) designed to be applied topically for the management of diabetic wounds. Hydroxypropyl methyl cellulose (HPMC) of different molecular weight (E5, K4M or K15M) were used, in different ratios, with chitosan (CS) for the preparation of the 3D-SC. Investigations to examine the prepared SCs revealed that SC-F3 composed of CS /HPMC E5 (2:1) attained the highest porosity (99.12 ±â€¯5.01), highest water absorption capacity % (300.09 ±â€¯20.20), and attained the fastest drug release profile (p < 0.05), with release kinetics following the diffusion model. SEM microphotographs showed the highly porous structure of SC-F3. According to the modified Draize test, the selected 3D-SC (the medicated as well as the unmedicated) showed to be safe for skin application (PII = 0). During the in-vivo studies, both the selected PG-loaded SC and the unmedicated SC showed a significant improvement in the healing process compared to the untreated group, this was evidenced by the measurement of wound contraction % [627% and 467%, respectively, p < 0.05], as well as the level of some biomarkers (TNF-α, VEGF and MMP-9). PG-loaded SC had a significantly better effect than the unmedicated SC (p < 0.05). Histopathological studies confirmed the complete tissue regeneration and healing process after the use of the selected PG-loaded scaffolds. The current study presents a feasible approach to support diabetic wound healing using a simple and safe formulation.


Assuntos
Diabetes Mellitus Experimental/complicações , Pioglitazona/química , Pioglitazona/farmacologia , Polímeros/química , Tecidos Suporte/química , Cicatrização/efeitos dos fármacos , Animais , Bandagens , Quitosana/química , Liberação Controlada de Fármacos/efeitos dos fármacos , Derivados da Hipromelose/química , Masculino , Porosidade , Estudo de Prova de Conceito , Ratos , Ratos Wistar , Pele/efeitos dos fármacos
8.
Int J Pharm ; 570: 118657, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31491483

RESUMO

Avanafil (AVA) is a recent FDA approved selective phosphodiesterase type 5 inhibitor used for oral treatment of erectile dysfunction. The oral bioavailability of the drug is challenged by its reduced water solubility, considerable presystemic metabolism, and altered absorption in the presence of food. Accordingly, this work aimed to surmount the aforementioned challenges through the development of optimized nanosized AVA invasomes with enhanced transdermal delivery. AVA invasomes were prepared according to a Box-Behnken experimental design to explore the impact of the following formulation factors: phospholipid % (X1), ethanol % (X2), terpene % (X3), and terpene type (X4) on vesicle size (Y1) and entrapment efficiency (Y2). The three numerical variables were used at three levels, while the categorical variable was used at two levels. The optimized formulation with vesicular size of 109.92 nm and entrapment efficiency of 96.98% was incorporated into a hydroxypropyl methyl cellulose-based transdermal film and characterized for its ex vivo permeation behavior and in vivo performance in rats. The optimized AVA invasomal film showed enhanced ex vivo permeation with an enhancement factor of 2.514 and a more than four-fold increase in relative bioavailability compared to the raw AVA film. These results provide insight into the capability of the optimized invasomal film to enhance the transdermal permeation and bioavailability of AVA.


Assuntos
Pirimidinas/administração & dosagem , Pirimidinas/química , Pele/metabolismo , Administração Cutânea , Administração Oral , Animais , Disponibilidade Biológica , Química Farmacêutica/métodos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Derivados da Hipromelose/química , Masculino , Tamanho da Partícula , Permeabilidade/efeitos dos fármacos , Inibidores da Fosfodiesterase 5/administração & dosagem , Inibidores da Fosfodiesterase 5/química , Ratos , Ratos Wistar , Absorção Cutânea/efeitos dos fármacos , Solubilidade/efeitos dos fármacos
9.
Int J Nanomedicine ; 14: 6287-6296, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496686

RESUMO

Purpose: We aimed to enhance the solubility, dissolution rate, oral bioavailability, and α-glucosidase inhibition of glimepiride (Glm) by fabricating its nanosuspension using a precipitation-ultrasonication approach. Methods: Glm nanosuspensions were fabricated using optimized processing conditions. Characterization of Glm was performed using Malvern Zetasizer, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. Minimum particle size and polydispersity index (PDI) values were found to be 152.4±2.42 nm and 0.23±0.01, respectively, using hydroxypropyl methylcellulose: 6 cPs, 1% w/v, polyvinylpyrrolidone K30 1% w/v, and sodium lauryl sulfate 0.12% w/v, keeping ultrasonication power input at 400 W, with 15 minutes' processing at 3-second pauses. In vivo oral bioavailability was assessed using rabbits as a model. Results: The saturation solubility of the Glm nanosuspensions was substantially enhanced 3.14-fold and 5.77-fold compared to unprocessed drug in stabilizer solution and unprocessed active pharmaceutical ingredient. Also, the dissolution rate of the nanosuspensions ws substantially boosted when compared to the marketed formulation and unprocessed drug candidate. The results showed that >85% of Glm nanosuspensions dissolved in the first 10 minutes compared to 10.17% of unprocessed Glm), 42.19% of microsuspensions, and 19.94% of marketed tablets. In-vivo studies conducted in animals, i.e. rabbits, demonstrated that maximum concentration and AUC0-24 with oral dosing were twofold (5 mg/kg) and 1.74-fold (2.5 mg/kg) and 1.80-fold (5 mg/kg) and 1.63-fold (2.5 mg/kg), respectively, and compared with the unprocessed drug formulation. In-vitro α-glucosidase inhibition results showed that fabricated nanosuspensions had a pronounced effect compared to unprocessed drug. Conclusion: The optimized batch fabricated by ultrasonication-assisted precipitation can be useful in boosting oral bioavailability, which may be accredited to enhanced solubility and dissolution rate of Glm, ultimately resulting in its faster rate of absorption due to nanonization.


Assuntos
Precipitação Química , Inibidores de Glicosídeo Hidrolases/farmacologia , Nanopartículas/química , Compostos de Sulfonilureia/farmacologia , Ultrassom , alfa-Glucosidases/metabolismo , Administração Oral , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Derivados da Hipromelose/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Coelhos , Solubilidade , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/química , Compostos de Sulfonilureia/farmacocinética , Suspensões , Difração de Raios X
10.
Eur J Pharm Biopharm ; 144: 79-90, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499162

RESUMO

Despite the fact that solid dispersions are gaining momentum, the number of polymers that have been used as a carrier during the past 50 years is rather limited. Recently, the poly(2-alkyl-2-oxazoline) (PAOx) polymer class profiled itself as a versatile platform for a wide variety of applications in drug delivery, including their use as amorphous solid dispersion (ASD) carrier. The aim of this study was to investigate the potential of poly(2-ethyl-2-oxazoline) (PEtOx) by applying a benchmark approach with well-known, commercially available carriers (i.e. polyvinylpyrrolidone (PVP) K30, poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) 64 and hydroxypropylmethylcellulose (HPMC)). For this purpose, itraconazole (ITC) and fenofibrate (FFB) were selected as poorly water-soluble model drugs. The four polymers were compared by establishing their supersaturation maintaining potential and by investigating their capability as carrier for ASDs with high drug loadings. Spray drying, as well as hot melt extrusion and cryo-milling were implemented as ASD manufacturing technologies for comparative evaluation. For each manufacturing technique, the formulations with the highest possible drug loadings were tested with respect to in vitro drug release kinetics. This study indicates that PEtOx is able to maintain supersaturation of the drugs to a similar extent as the commercially available polymers and that ASDs with comparable drug loadings can be manufactured. The results of the in vitro dissolution tests reveal that high drug release can be obtained for PEtOx formulations. Overall, proof-of-concept is provided for the potential of PEtOx for drug formulation purposes.


Assuntos
Portadores de Fármacos/química , Poliaminas/química , Solubilidade/efeitos dos fármacos , Química Farmacêutica/métodos , Cristalização/métodos , Dessecação/métodos , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Derivados da Hipromelose/química , Polímeros/química , Povidona/química , Pirrolidinas/química , Compostos de Vinila/química
11.
AAPS PharmSciTech ; 20(8): 308, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520165

RESUMO

Quantitative structure-property relationship (QSPR) approach has been widely used in predicting physicochemical properties of compounds. However, its application in the estimation of formulation properties based on the polymer used in it to achieve desired formulation characteristics is an extremely challenging process. In the present research, predictive QSPR models were developed by correlating the physicochemical properties of varying grades of cellulose ethers (hydroxypropyl methylcellulose, HPMC) with those of nateglinide (NTG) containing tablets (in vitro and in vivo properties). Sustained release tablets of NTG were prepared by using different grades and concentrations of HPMC and subsequently characterized for in vitro as well as in vivo parameters. Further, QSPR models for individual formulation property were developed by correlating the polymeric physicochemical properties with the formulation characteristics. Subsequently, a true external validation method was used to validate the predictability of developed models. The dissolution study indicated Korsmeyer-Peppas as the best fit model following non-Fickian as drug transport mechanism extending the drug release up to 12 h. In vivo studies showed limited absorption of the NTG. Developed QSPR models showed promising validated predictability for formulation characteristics. The applicability of present work in formulation development could significantly reduce the time and cost expenditure on design trials without actually formulating a delivery system.


Assuntos
Excipientes/química , Derivados da Hipromelose/química , Animais , Simulação por Computador , Preparações de Ação Retardada , Composição de Medicamentos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Modelos Químicos , Nateglinida/administração & dosagem , Nateglinida/química , Nateglinida/farmacocinética , Polimerização , Relação Quantitativa Estrutura-Atividade , Coelhos , Reprodutibilidade dos Testes , Comprimidos
12.
Drug Dev Ind Pharm ; 45(10): 1695-1706, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31418592

RESUMO

Objectives: Development and evaluation of rapidly dissolving film for intra-oral administration of naftopidil. Significance: Formulation of naftopidil in the form of rapidly dissolving buccal film can eliminate the dissolution problem of naftopidil and provide a greater chance for direct absorption into the systemic circulation bypassing the presystemic metabolism. This can improve the oral bioavailability. In addition, this film guarantees patient compliance and is suitable for geriatric patients. Methods: Rapidly dissolving film utilized hydroxypropyl methylcellulose E5 and polyvinylpyrrolidone K30 as the main components. The drug was loaded in pure form or after co-grinding with citric and/or tartaric acid. A solution of naftopidil in plurol oleique, labrasol, and tween 80 self-microemulsifying drug delivery systems (SMEDDS) was also loaded. The interactions of the drug with the excipients were monitored using thermal analysis, Fourier transform infrared spectroscopy, and X-ray diffraction. Naftopidil dissolution was monitored and selected films were used to assess the bioavailability after buccal administration to rabbit. Unprocessed drug suspension was administered orally and used as a reference. Results: Incorporation of naftopidil in the film developed a new crystalline structure. The crystallinity of drug was abolished in the presence of organic acids or SMEDDS. The rapidly dissolving films showed fast liberation of the drug irrespective to the composition. Those films enhanced the bioavailability of naftopidil compared to orally administered suspension with SMEDDS containing film being superior. Conclusion: The study introduced rapidly dissolving buccal film for enhanced dissolution and bioavailability of naftopidil.


Assuntos
Excipientes/química , Naftalenos/administração & dosagem , Naftalenos/química , Piperazinas/administração & dosagem , Piperazinas/química , Solubilidade/efeitos dos fármacos , Administração Bucal , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Derivados da Hipromelose/química , Povidona/química , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Suspensões/química , Difração de Raios X/métodos
13.
Int J Pharm ; 570: 118607, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31421200

RESUMO

The aim of this study was to evaluate the influence of tableting process parameters, i.e. turret rotation speed, pre-compaction and main compaction pressures, and their interactions on layer adhesion of bilayer tablets. The elastic recovery after compaction was used as estimation for the elasticity of the material. Three potential pharmaceutical formulations were evaluated as combinations of immediate (microcrystalline cellulose, lactose, calcium phosphate, pregelatinized starch) and controlled drug release excipients (ethyl cellulose, hydroxypropyl methylcellulose, polyvinyl acetate/polyvinylpyrrolidone). A 3-levels 3-factors central composite Design of Experiment was performed on each formulation, with layer adhesion selected as response. A custom-made shear test was used to determine the tablet tendency to delaminate. Main compaction and turret rotation speed were the most important parameters to be optimized during tablet manufacturing. Main compaction was the principal parameter leading to delamination in case of formulations with plastic materials, particularly at high pressures where the difference in elasticity of excipients had a major impact and was followed by turret rotation speed. The rotation speed did not have an effect on layer adhesion in the case of formulations with brittle excipients.


Assuntos
Comprimidos/química , Fosfatos de Cálcio/química , Celulose/análogos & derivados , Celulose/química , Química Farmacêutica/métodos , Elasticidade , Excipientes/química , Derivados da Hipromelose/química , Lactose/química , Povidona/química , Pressão , Amido/química , Estresse Mecânico , Tecnologia Farmacêutica/métodos
14.
Eur J Pharm Sci ; 138: 105035, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31386892

RESUMO

Amorphous drug-polyelectrolyte nanoparticle complex (or nanoplex in short) has emerged as a highly attractive solubility enhancement strategy of poorly-soluble drugs attributed to its simple and highly efficient preparation. The existing nanoplex formulation, however, exhibits poor amorphous form stability during long-term storage for drugs with high crystallization propensity. Using ciprofloxacin (CIP) and sodium dextran sulfate (DXT) as the model drug-polyelectrolyte nanoplex, we investigated the feasibility of incorporating crystallization inhibiting agents, i.e. hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP), at the nanoplex formation step to improve the physical stability of the CIP nanoplex. The effects of the HPMC or PVP additions on the nanoplex's physical characteristics (i.e. size, zeta potential, CIP payload), CIP utilization rate, dissolution rate, and supersaturation generation were also examined. The results showed that the additions of HPMC or PVP increased the CIP nanoplex size (from 300 to 500 nm) and CIP utilization rate (from 65% to 90% w/w) with minimal impacts on the CIP payload (70-80% w/w). Their additions had opposite impacts on the nanoplex's colloidal stability due to surfactant nature of PVP. Significantly, unlike the CIP-DXT and CIP-DXT-PVP nanoplexes, the CIP-DXT-HPMC nanoplex remained amorphous after three-month accelerated storage, while also exhibited superior solubility enhancement (15-30% higher).


Assuntos
Derivados da Hipromelose/química , Nanopartículas/química , Polieletrólitos/química , Povidona/química , Ciprofloxacino/química , Cristalização/métodos , Sulfato de Dextrana/química , Portadores de Fármacos/química , Tamanho da Partícula , Solubilidade/efeitos dos fármacos
15.
AAPS PharmSciTech ; 20(7): 284, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31407165

RESUMO

This report aimed to formulate self-micro-emulsifying (SMEDDS) controlled-release pellets delivery system to improve aqueous solubility and in vivo availability of eugenol, a main constituent of clove oil with multiple pharmacological activities. The optimal formulation of eugenol-SMEDDS was eugenol: ethyl oleate: cremophor EL: 1, 2-propylene glycol at the ratio of 5:5:12:8. The SMEDDS were observed under transmission electron microscopy (TEM), and the size distribution was measured with dynamic laser light scatting (DLS). The particle size, index of dispersity (PDI), and zeta potential (Z-potential) were 68.8 ± 0.1 nm, 0.285 ± 0.031, and - 11.62 ± 0.63 mV, respectively. Eugenol-SMEDDS exhibited substantial increased in vitro dissolution compared with the free eugenol. The eugenol-SMEDDS sustained-release pellets (eugenol-SMEDDS-SR pellets) comprising of eugenol-SMEDDS, hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), and ethyl cellulose (EC) coats were obtained via extrusion spheronization technique. Consequently, the obtained pellets observed under scanning electron microscopy (SEM) showed spherical shape with smooth surface, desirable drug loading capacity (7.18 ± 0.17%), greater stability, and controlled release. Meanwhile, the oral test showed that bioavailability of eugenol in pellets was highly improved 23.6-fold to the free eugenol. Overall, these results suggested that the improvement of the oral bioavailability of eugenol-SMEDDS-SR could be due to the successful incorporation of the drug into SMEDDS.


Assuntos
Eugenol/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Celulose/análogos & derivados , Celulose/química , Química Farmacêutica/métodos , Preparações de Ação Retardada , Cães , Emulsões/química , Eugenol/administração & dosagem , Eugenol/química , Derivados da Hipromelose/química , Tamanho da Partícula , Polietilenoglicóis/química
16.
Int J Pharm ; 570: 118643, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31446023

RESUMO

Although vaginal films were initially developed for a fast release of the drug, with the adequate formulation they can also be useful for sustained release. The latest strategies for the prevention of the sexual transmission of HIV have moved towards sustained-release dosage forms, so films may be an effective strategy that could also improve the patient's comfort. A hydrophilic polymer (hydroxypropylmethyl cellulose) and an amphiphilic polymer (zein) have been evaluated for the development of Tenofovir sustained-release vaginal films. The modification of the film's properties by the inclusion of polar (glycerol and polyethylene glycol 400 (PEG)) and amphiphilic (tributyl citrate and oleic acid) plasticisers was also evaluated. The films' physicochemical and mechanical properties were determined. The in vitro release of Tenofovir from the films and their bioadhesive capacity and behaviour in simulated vaginal fluid were also assessed. The combination of hydroxypropylmethyl cellulose and zein in films (ratio 1:5), with the inclusion of PEG (40% w/w) proved not only to have excellent mechanical properties, but was also able to release TFV in a sustained manner for 120 h and remain attached to biological tissues throughout this time. This film could be an interesting option for the prevention of sexual transmission of HIV.


Assuntos
Adesivos/química , Fármacos Anti-HIV/química , Infecções por HIV/prevenção & controle , Derivados da Hipromelose/química , Polímeros/química , Vagina/efeitos dos fármacos , Zeína/química , Adesivos/administração & dosagem , Administração Intravaginal , Animais , Fármacos Anti-HIV/administração & dosagem , Linhagem Celular , Química Farmacêutica/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Feminino , Glicerol/química , Humanos , Polietilenoglicóis/química , Doenças Sexualmente Transmissíveis/prevenção & controle , Células THP-1 , Tenofovir/administração & dosagem , Tenofovir/química
17.
Int J Biol Macromol ; 137: 1013-1019, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31299251

RESUMO

Photophobic (white) films were prepared by mixing hydroxypropyl methylcellulose (HPMC) of different molecular weights with sodium citrate (SC). Wide angle X-ray diffractometry, small angle X-ray scattering, scanning electron microscopy, dynamic mechanical analysis, whiteness determination and texture analysis were used to investigate the effect of HPMC molecular weight on the aggregation structures and properties of HPMC film. The crystalline integrity decreased with the increased molecular weight of HPMC for these HPMC/SC films. Similar crystallinity was observed for 6HPMC/SC and 15HPMC/SC, which was larger than that of 50HPMC/SC. All the three HPMC/SC film showed surface fractal structure with similar Ds. With the increasing molecular weight of HPMC, the HPMC/SC film showed honeycomb structures with smaller holes and more compact porous structure, Tg first increased and then decreased a little, the tensile strength and elongation increased with the increasing HPMC molecular weight. 50HPMC/SC films with the smallest pores showed the largest whiteness. A new Tg' peak was observed for HPMC/SC film.


Assuntos
Derivados da Hipromelose/química , Luz , Citrato de Sódio/química , Fenômenos Mecânicos , Peso Molecular
18.
ACS Appl Mater Interfaces ; 11(32): 28740-28751, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31334627

RESUMO

Electrospinning provides a simple and convenient method to fabricate nanofibrous meshes. However, the nanofiber productivity is often limited to the laboratory scale, which cannot satisfy the requirements of practical application. In this study, we developed a novel needleless electrospinning spinneret based on a double-ring slit to fabricate drug-loaded nanofibrous meshes. In contrast to the conventional single-needle electrospinning spinneret, our needless spinneret can significantly improve nanofiber productivity due to the simultaneous formation of multiple jets during electrospinning. Curcumin-loaded poly(l-lactic acid) (PLLA) nanofiber meshes with various concentrations and on the large scale were manufactured by employing our developed needleless spinneret-based electrospinning device. We systematically investigated the drug release behaviors, antioxidant properties, anti-inflammatory attributes, and cytotoxicity of the curcumin-loaded PLLA nanofibrous meshes. Furthermore, a bilayer nanofibrous composite mesh was successfully generated by electrospinning curcumin-loaded PLLA solution and diclofenac sodium loaded poly(ethylene oxide) solution in a predetermined time sequence, which revealed potent antibacterial properties. Subsequently, novel mucoadhesive patches were assembled by combining the bilayer composite nanofibrous meshes with (hydroxypropyl)methyl cellulose based mucoadhesive film. The multilayered mucoadhesive patch has excellent adhesion properties on the porcine buccal mucosa. Overall, our double-ring slit spinneret can provide a novel method to rapidly produce large-scale drug-loaded nanofibrous meshes to fabricate mucoadhesive patches. The multiple-layered mucoadhesive patches enable the incorporation of multiple drugs with different targets of action, such as analgesic, anti-inflammatory, and antimicrobial compounds, for mouth ulcer or other oral disease treatments.


Assuntos
Adesivos , Curcumina , Derivados da Hipromelose , Nanofibras/química , Úlceras Orais/terapia , Adesivos/química , Adesivos/farmacologia , Animais , Curcumina/química , Curcumina/farmacologia , Humanos , Derivados da Hipromelose/química , Derivados da Hipromelose/farmacologia , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Úlceras Orais/metabolismo , Úlceras Orais/patologia , Suínos
19.
Pak J Pharm Sci ; 32(3 (Supplementary)): 1245-1251, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31303597

RESUMO

The aim of the current study was to formulate sustain release (SR) tablets of ketoprofen. Five batches (batch I -V) of matrix based ketoprofen tablet were prepared by dry granulation method using hydroxyl propyl methyl cellulose (15000cps). Compatibility of formulation excipients with drug was explored through FT-IR technique. Various physical and chemical parameters of all tablet batches were evaluated with multi-point dissolution profile (for 24hrs) for formulation optimization. Release kinetics of trials was estimated by model dependent and independent methods. Formulations having excellent quality attributes were then compared with marketed ketoprofen SR tablets. Accelerated stability study was also conducted to compute the shelf life of the optimized formulation. FT-IR scans illustrated the compatibility of ketoprofen with all tablet excipients. On the basis of testing results and controlled release pattern batch II was set to be an optimized trial having shelf life of 37 months. All trial batches (batch I-V) and the marketed brand exhibited highest linearity towards zero order and Korsmeyer-Peppas model with non-fickian anomalous transport (n=0.541-0.655).


Assuntos
Cetoprofeno/química , Cetoprofeno/farmacocinética , Comprimidos/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Excipientes/química , Derivados da Hipromelose/química , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos/farmacocinética
20.
Int J Pharm ; 568: 118554, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31336153

RESUMO

The subdivision behavior of polymeric tablets produced with the well-known polymers Soluplus® (SOL), polyvinyl pyrrolidone co-vinyl acetate (PVPVA) and hydroxypropyl methylcellulose (HPMC) was evaluated in this study. The polymeric tablets were submitted to different post-treatments (aging, thermal and exposure to compressed gaseous carbon dioxide) and its mechanical, spectroscopic and microstructure properties were assessed. SOL tablets showed the best results for tablet subdivision, particularly, the mean mass variation (3.9%) was significantly lower than the other two polymeric tablets (7.2% and 9.1% for PVPVA and HPMC, respectively), and showed better results than common tablets produced from powder matrices (7-14%). SOL tablets were also more sensitive to the different post-treatments applied, which reduced the mass loss and friability from 1.5% and 0.8%, respectively, to values close to zero and without altering their porosity. The thermal treatment of PVPVA tablets, in turn, also led to similar subdivision results, with mass loss of 0.3% and friability of 0.02%. In contrast, the granules of HPMC presented compaction difficulties making its tablets unsuitable for the subdivision process, even after additional post-treatment. Polymeric matrices with uniform internal structure and appropriate mechanical strength are the key to a better adaptation for the tablet subdivision.


Assuntos
Derivados da Hipromelose/química , Polietilenoglicóis/química , Polivinil/química , Povidona/análogos & derivados , Dióxido de Carbono/química , Temperatura Alta , Povidona/química , Comprimidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA