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1.
Eur J Pharm Biopharm ; 145: 113-120, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31682903

RESUMO

Lipid-based drug delivery systems (LBDDS) are highly relevant as pharmaceutical formulations significantly enhancing the bioavailability of active pharmaceutical ingredients (APIs). These formulations often are complex mixtures of APIs, various lipids, and other excipients (e.g. surfactants). In their simplest form, LBDDS contain one API being dissolved in a pure lipid, which often is a triglyceride (TG). In this work, solubilities of the APIs indomethacin, ibuprofen, and fenofibrate in pure TGs of different chain lengths (C chain 8-18) and degree of saturation were investigated. Solubilities of APIs in TGs were measured via differential scanning calorimetry, hot-stage microscopy, high-performance liquid chromatography, and Raman spectroscopy. The influence of fatty-acid chain length and degree of saturation on the API solubility in the TGs was investigated. APIs showed a higher solubility in saturated (wIBU = 10.5 wt% at 25 °C in tricaprylin) TGs compared to unsaturated ones (wIBU = 4.0 wt% at 25 °C in triolein). The fatty-acid chain length of TGs only slightly affects the solubility of ibuprofen and fenofibrate, but strongly influences the eutectic temperature of the API/TG mixtures. API solubilities in TGs and TG mixtures (mixtures of tricaprylin and tricaprin) were successfully modeled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) accounting for the intermolecular API/TG interactions providing a deep understanding of the energetic and structural impact of the TGs on API solubility.


Assuntos
Preparações Farmacêuticas/química , Solubilidade/efeitos dos fármacos , Triglicerídeos/química , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Excipientes/química , Fenofibrato/química , Ibuprofeno/química , Indometacina/química , Lipídeos/química
2.
Expert Opin Ther Pat ; 29(11): 891-907, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31603360

RESUMO

Introduction: Pharmacotherapy is limited by the inefficient drug targeting of non-healthy cells/tissues. In this pharmacological landscape, liposomes are contributing to the impulse given by Nanotechnology to optimize drug therapy. Areas covered: The analysis of the state-of-the-art in liposomal formulations for drug delivery purposes have underlined that lately published patents (since 2014) are exploring alternative compositions and ways to optimize the stability and drug loading content/release profile. These improvements are complemented by improved long-circulating structures and further liposome functionalizations, which have definitively opened the road for the (co-)delivery of therapeutics to the site of action. Liposomes are also contributing to new drug delivery approaches involving the generation of extracellular vesicles by targeted cells, while opening new ways to combine disease diagnosis and therapy (theranosis). Expert opinion: Patent publications on liposomal formulations have expanded new ways in drug delivery. New lipid compositions and strategies to optimize stability and drug vehiculization capabilities have settle solid pillars in liposome fabrication. Despite, their architecture has been satisfactorily adapted for combining passive and active drug targeting concepts, new inputs of liposomes into the disease arena should answer for: a simple/scalable/cost-effective formulation; a safe/stable/controllable formulation meeting quality control regulations; and, a confirmed therapeutic efficiency in clinical investigations.


Assuntos
Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos , Lipídeos/química , Animais , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Lipossomos , Nanotecnologia/métodos , Patentes como Assunto
3.
Sud Med Ekspert ; 62(5): 47-53, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31626195

RESUMO

Falsification and use of low-quality drugs of biological origin creates a threat to public health. To a greater extent, costly drugs, including bevacizumab, are exposed to similar abuses. Timely determination of cases of forgery or the improper clinical use of monoclonal antibody preparations is one of the necessary measures that can be taken to limit the risks and preserve the health of patients. This paper presents the results of the investigation of the bevacizumab preparation 'Avastin', which was withdrawn from ophthalmic clinical practice in the course of the investigation. We compared the qualitative and quantitative composition of the drug samples, which were determined using commonly available methods of chemical and toxicological analysis.


Assuntos
Bevacizumab/análise , Química Farmacêutica/métodos , Medicamentos Falsificados/análise
4.
Eur J Pharm Biopharm ; 145: 35-41, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31568821

RESUMO

Film coating of nifedipine tablets is commonly performed to reduce photo-degradation. The coating thickness of these tablets is a primary dictating factor of photo-stability. Terahertz spectroscopy enables accurate measurement of coating thickness. This study identifies a method to determine an end-point of a photo-protective coating process by using coating thickness measurements from terahertz time of flight spectroscopy (THz-TOF). For this method, nifedipine tablets, at different coating thicknesses, were placed in a photostability chamber. The illumination conditions of the coated tablets were adjusted based on the time duration of these tablets inside the chamber. A multiple linear regression model was developed with the coating thickness estimates from THz-TOF and illumination conditions information to predict the amount of drug remaining after photo-degradation (percent label claim). The prediction error of this model was 1.03% label claim in the range of 88.4-100.6% label claim. According to this model, acceptable levels of photo-protection in illumination conditions of up to approximately 700,000 lx hours was achieved at the end of the coating process (approximately 50 µm coating thickness) performed in this study. These results suggest THz-TOF as a viable process analytical technology tool for process understanding and end-point determination of a photo-protective coating process.


Assuntos
Nifedipino/química , Fotólise/efeitos dos fármacos , Comprimidos com Revestimento Entérico/química , Comprimidos/química , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Excipientes/química , Propriedades de Superfície/efeitos dos fármacos , Imagem Terahertz/métodos
5.
Eur J Pharm Biopharm ; 145: 7-11, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31605741

RESUMO

The usefulness, the high production rate and the cost effectiveness make tablets the dosage form of choice for oral probiotics. Nevertheless, probiotic bacteria undergo a lot of mechanical stress during tableting which causes damage to their cell wall and membrane and other bio-active components. This can lead to an inactivation of the probiotic bacteria and therefore in a failure of the probiotic therapy. To obtain a tablet with a sufficient amount of viable cells, research on the influence of formulation and process parameters on bacterial survival is essential. This study aimed to decipher tableting properties of the probiotic powder blends that have a major impact on survival rates. The powder blends consisted of the prototype probiotic strain Lactobacillus rhamnosus GG, a filler-binder and a suitable amount of lubricant. They were manufactured by direct compression at different compression pressures and tableting speeds. The tableting properties were analysed in detail by a 3-D modelling technique, which characterized normalized time, pressure and displacement simultaneously. The results of the 3-D modelling demonstrated the significant effect of the pressure plasticity (e) and the angle of rotation (ω) on the viability of L. rhamnosus GG during direct compression.


Assuntos
Força Compressiva/efeitos dos fármacos , Probióticos/química , Comprimidos/química , Química Farmacêutica/métodos , Excipientes/química , Lactobacillus rhamnosus/química , Pós/química , Pressão
7.
Eur J Pharm Biopharm ; 144: 68-78, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31493511

RESUMO

Medicated chewing gums represent an orally administered dosage form with promising potential for local and systemic drug delivery. However, compared to other solid oral dosage forms, formulation development and release mechanism of medicated chewing gums are extremely complex, and thus only few products reached the approval for the market so far. Therefore, Quality by Design (QbD) approaches for rational formulation development of medicated chewing gums are needed to utilize their full potential. For chewing gum tablets, which are manufactured by direct compression, QbD approaches derived from tableting processes might be exerted. In this context, the SeDeM-Diagram-Expert-System implements the QbD approach while indicating whether a blend is suitable for direct compression and comprises powder properties, which need to be improved to facilitate the formulation development. Here, we present the successful application of the SeDeM-Diagram-Expert-System to the formulation development of medicated chewing gum tablets manufactured by direct compression. Furthermore, limitations of the SeDeM-System for medicated chewing gum tablets are evaluated and potential modifications of the system are suggested and discussed for future use.


Assuntos
Comprimidos/química , Química Farmacêutica/métodos , Goma de Mascar , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Excipientes/química , Sistemas Especialistas , Pós/química
8.
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
9.
Eur J Pharm Biopharm ; 144: 139-153, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31536784

RESUMO

Trehalose is commonly used as a protein stabilizer in spray dried protein formulations delivered via the pulmonary route. Spray dried trehalose formulations are highly hygroscopic, which makes them prone to deliquescence and recrystallization when exposed to moisture, leading to impairment in aerosolization performance. The main aim of this study was to investigate and compare the effect of hydrophobic amino acids (i.e. L-leucine and L-isoleucine) in enhancing aerosolization performance and in mitigating moisture-induced changes in spray dried trehalose formulations. Trehalose was spray dried with 20-60% w/w of amino acid (i.e. L-leucine or L-isoleucine). The spray dried formulations were stored at 25 °C/50% RH for 28 days. Solid state characterization and in vitro aerosolization performance studies were performed on the spray dried formulations before and after storage. The addition of 20-60% w/w of amino acid (i.e. L-leucine or L-isoleucine) improved the emitted fractions of spray dried trehalose formulations from a dry powder inhaler. However, ≥ 40% w/w of L-leucine/L-isoleucine was needed to prevent recrystallization of trehalose in the formulations when exposed to 25 °C/50% RH for 28 days. X-ray photoelectron spectroscopy (XPS) demonstrated that samples with 40-60% w/w L-isoleucine had more amino acid on the surfaces of the particles compared to their L-leucine counterparts. This may explain the greater ability of the L-isoleucine (40-60% w/w) samples to cope with elevated humidity compared to L-leucine samples of the same concentrations, as observed in the dynamic vapour sorption (DVS) studies. In conclusion, this study demonstrated that both L-leucine and L-isoleucine were effective in enhancing aerosolization performance and mitigating moisture-induced reduction in aerosolization performance in spray dried trehalose formulations. L-isoleucine proved to be superior to L-leucine in terms of its moisture protectant effect when incorporated at the same concentration in the formulations.


Assuntos
Aminoácidos/química , Trealose/química , Administração por Inalação , Aerossóis/química , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Inaladores de Pó Seco/métodos , Umidade , Interações Hidrofóbicas e Hidrofílicas , Leucina/química , Pós/química , Molhabilidade/efeitos dos fármacos
10.
Eur J Pharm Biopharm ; 144: 174-179, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31541663

RESUMO

Capsules are a widely used oral dosage form due to their simplicity and ease of manufacture. They are equally popular for both pharmaceutical and nutraceutical products and since they do not need extensive formulation development, it is a dosage form of choice for new drugs undergoing animal or clinical trials. In addition to the standard hard-gelatin or cellulose-based vegetarian capsules, functional capsules such as those with built-in gastroresistance would be of great value. In this work, commonly used enteric polymers were investigated for the production of hard-capsules. The polymers used in this study included cellulose derivatives (HPMC AS-LF and HP-55) and acrylic/methacrylic acid derivatives (EUDRAGIT L100 and S100). A range of concentrations of polymers and plasticisers were tested to optimise the formulation for the production of capsule shells with desirable physicochemical and gastroresistance characteristics. Drug release from optimised capsules produced from HPMC AS-LF, HP-55, EUDRAGIT L100 and S100 was shown to be comparable to drug release from corresponding polymer-coated tablets in both compendial and physiological bicarbonate buffer. In summary, herein we report a simple method for producing enteric capsule shells which do not need an additional coating step which, if validated at large scale, can significantly reduce the cost of manufacturing of conventional enteric coated dosage forms. These capsules are also likely to improve the inter-tablet variability in post-gastric drug release inherent in conventional dosage forms due to coating variability.


Assuntos
Cápsulas/química , Polímeros/química , Bicarbonatos/química , Tampões (Química) , Celulose/química , Química Farmacêutica/métodos , Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Excipientes/química , Gelatina/química , Concentração de Íons de Hidrogênio , Metacrilatos/química , Metilcelulose/análogos & derivados , Metilcelulose/química , Ácidos Polimetacrílicos/química , Solubilidade/efeitos dos fármacos , Comprimidos/química
11.
Eur J Pharm Biopharm ; 144: 18-39, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31446046

RESUMO

Development of nanocarriers for drug delivery has received considerable attention due to their potential in achieving targeted delivery to the diseased site while sparing the surrounding healthy tissue. Safe and efficient drug delivery has always been a challenge in medicine. During the last decade, a large amount of interest has been drawn on the fabrication of surfactant-based vesicles to improve drug delivery. Niosomes are self-assembled vesicular nano-carriers formed by hydration of non-ionic surfactant, cholesterol or other amphiphilic molecules that serve as a versatile drug delivery system with a variety of applications ranging from dermal delivery to brain-targeted delivery. A large number of research articles have been published reporting their fabrication methods and applications in pharmaceutical and cosmetic fields. Niosomes have the same advantages as liposomes, such as the ability to incorporate both hydrophilic and lipophilic compounds. Besides, niosomes can be fabricated with simple methods, require less production cost and are stable over an extended period, thus overcoming the major drawbacks of liposomes. This review provides a comprehensive summary of niosomal research to date, it provides a detailed overview of the formulation components, types of niosomes, effects of components on the formation of niosomes, fabrication and purification methods, physical characterization techniques of niosomes, recent applications in pharmaceutical field such as in oral, ocular, topical, pulmonary, parental and transmucosal drug delivery, and cosmetic applications. Finally, limitations and the future outlook for this delivery system have also been discussed.


Assuntos
Cosméticos/química , Lipossomos/química , Surfactantes Pulmonares/química , Tensoativos/química , Administração Cutânea , Animais , Química Farmacêutica/métodos , Colesterol/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos
12.
Eur J Pharm Biopharm ; 142: 543-552, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31398437

RESUMO

Recently we showed that nebulized ciprofloxacin and phage PEV20 in combination had a synergistic bactericidal effect against antibiotic-resistant Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Compared to nebulization, dry powders for inhalation may improve patient handling characteristics and compliance. In the present study, we co-spray dried ciprofloxacin and phage PEV20 using L-leucine with or without lactose as excipients. Two formulations were identified for testing in this study. The mass ratios were set at 1:1:1 for ciprofloxacin, lactose and L-leucine (Formulation A) or 2:1 for ciprofloxacin and L-leucine without lactose (Formulation B). Concentrations of PEV20 were set at 108 and 109 PFU/mL for two clinical P. aeruginosa strains FADD1-PA001 and JIP865, respectively. Formulations A and B were characterized as partially crystalline and the powders recrystallized at >40% relative humidity (RH). Both formulations exhibited strong synergistic antimicrobial killing effect on the two strains. Formulations A and B maintained bactericidal synergy after dispersion using both low and high resistance Osmohaler™. Powder aerosol performance was examined by next generation impactor (NGI) in low resistance inhaler at 100 L/min and by multi-stage liquid impinger (MSLI) in high resistance inhaler at 60 L/min. Fine particle fractions (FPF) obtained by NGI were 59.7 ±â€¯2.1% and 64.3 ±â€¯2.9% for A and B, respectively. FPF obtained by MSLI were 71.0 ±â€¯3.4% and 73.3 ±â€¯5.0%, respectively. In conclusion, it is feasible to prepare stable and inhalable combination powder formulations of phage PEV20 and ciprofloxacin for potential treatment of respiratory infections caused by multi-drug resistant (MDR) P. aeruginosa.


Assuntos
Bacteriófagos/classificação , Ciprofloxacino/administração & dosagem , Ciprofloxacino/química , Pós/química , Infecções Respiratórias/tratamento farmacológico , Administração por Inalação , Aerossóis/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Química Farmacêutica/métodos , Fibrose Cística/microbiologia , Inaladores de Pó Seco/métodos , Excipientes/química , Humanos , Lactose/química , Nebulizadores e Vaporizadores , Tamanho da Partícula , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos
13.
AAPS PharmSciTech ; 20(7): 297, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444661

RESUMO

Miconazole nitrate (MZ) is a BCS class II antifungal poorly water-soluble drug with limited dissolution properties and gastrointestinal side effects. Self-nanoemulsifying delivery system-based gel of MZ can improve both solubility and oral mucosal absorption with enhanced antifungal activity. The study aims to formulate MZ self-nanoemulsion (MZ-NE) and combine it within hyaluronic acid-based gel. MZ solubility in various oils, surfactants, and cosurfactant used in NE formulations were evaluated. Mixture design was implemented to optimize the levels of NE components as a formulation variable to study their effects on the mean globule size and antifungal inhibition zones. Further, the optimized MZ-NE was loaded into a hyaluronic acid gel base. Rheological behavior of the prepared gel was assessed. Ex vivo permeability of optimized formulation across buccal mucous of sheep and inhibition against Candida albicans were examined. Mixture design was used to optimize the composition of MZ-NE formulation as 22, 67, and 10% for clove oil, Labrasol, and propylene glycol, respectively. The optimized formulation indicated globule size of 113 nm with 29 mm inhibition zone. Pseudoplastic flow with thixotropic behavior was observed, which is desirable for oral gels. The optimized formulation exhibited higher ex vivo skin permeability and enhanced antifungal activity by 1.85 and 2.179, respectively, compared to MZ-SNEDDS, and by 1.52 and 1.72 folds, respectively, compared to marketed gel. Optimized MZ-NE hyaluronic acid-based oral gel demonstrated better antifungal activity, indicating its potential in oral thrush pharmacotherapy.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Bucal/tratamento farmacológico , Química Farmacêutica/métodos , Ácido Hialurônico/administração & dosagem , Miconazol/administração & dosagem , Nanocápsulas/administração & dosagem , Administração Oral , Animais , Antifúngicos/síntese química , Antifúngicos/farmacocinética , Candidíase Bucal/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Emulsões/administração & dosagem , Emulsões/síntese química , Emulsões/farmacocinética , Ácido Hialurônico/síntese química , Ácido Hialurônico/farmacocinética , Hidrogéis/administração & dosagem , Hidrogéis/síntese química , Hidrogéis/farmacocinética , Miconazol/síntese química , Miconazol/farmacocinética , Nanocápsulas/química , Ovinos
14.
Eur J Pharm Biopharm ; 143: 51-60, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31445156

RESUMO

Extensive research has been undertaken to investigate the effect of liposome size in vitro and in vivo. However, it is often difficult to generate liposomes in different size ranges that offer similar low polydispersity and lamellarity. Conventional methods used in the preparation of liposomes, such as lipid film hydration or reverse phase evaporation, generally give rise to liposomal suspensions displaying broad, multimodal size distribution combined with uncontrolled degree of lamellarity. In contrast, microfluidics allows highly homogeneous liposome dispersions to be produced and adjustment of microfluidic operating parameters (flow rate ratio (FRR) and total flow rate (TFR)) can offer size-tuning of liposomes (up to 300 nm, depending on the formulation). Herein, we demonstrate a novel method which allows the production of highly monodisperse, cationic liposomes over a wide particle size range (up to 750 nm in size). This is achieved through controlling the concentration of the aqueous buffer during production. Using this method, liposomes composed of 1,2-dioleoyl-sn-3-phosphoethanolamine (DOPE) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or dimethyldioctadecylammonium (DDA) - DOPE:DOTAP and DOPE:DDA liposomes - of up to 750 nm were prepared and investigated. These investigations demonstrate that the in vitro cellular uptake of small (40 nm) and large (>500 nm) liposomes in bone marrow-derived macrophages (BMDM) is similar terms of percentage of liposome+ cells and mean fluorescence intensity (MFI). However, significant differences are observed in BMDM uptake when represented in terms of number of liposomes, liposome surface area or liposome internal volume. In vivo biodistribution studies in mice show that by creating small (<50 nm) liposomes we can modify the clearance rates of these liposomes from the injection site and increase accumulation to the draining lymphatics.


Assuntos
Cátions/química , Cátions/metabolismo , Lipossomas Unilamelares/química , Lipossomas Unilamelares/metabolismo , Animais , Transporte Biológico/fisiologia , Química Farmacêutica/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microfluídica/métodos , Tamanho da Partícula , Compostos de Amônio Quaternário/química , Distribuição Tecidual/fisiologia
15.
Eur J Pharm Biopharm ; 143: 61-69, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31445157

RESUMO

Localized aerosol delivery of gene therapies is a promising treatment of severe pulmonary diseases including lung cancer, cystic fibrosis, COPD and asthma. The administration of drugs by inhalation features multiple benefits including an enhanced patient acceptability and compliance. The application of a spray dried powder formulation has advantages over solutions due to their increased stability and shelf life. Furthermore, optimal sizes of the powder can be obtained by spray drying to allow a deep lung deposition. The present study optimized the parameters involved with spray drying polyplexes formed by polyethylenimine (PEI) and nucleic acids in inert excipients to generate a nano-embedded microparticle (NEM) powder with appropriate aerodynamic diameter. Furthermore, the effects of the excipient matrix used to generate the NEM powder on the biological activity of the nucleic acid and the ability to recover the embedded nanoparticles was investigated. The study showed that bioactivity and nucleic acid integrity was preserved after spray drying, and that polyplexes could be reconstituted from the dry powders made with trehalose but not mannitol as a stabilizer. Scanning electron microscopy (SEM) showed trehalose formulations that formed fused, lightly corrugated spherical particles in the range between 1 and 5 µm, while mannitol formulations had smooth surfaces and consisted of more defined particles. After redispersion of the microparticles in water, polyplex dispersions are obtained that are comparable to the initial formulations before spray drying. Cellular uptake and transfection studies conducted in lung adenocarcinoma cells show that redispersed trehalose particles performed similar to or better than polyplexes that were not spray dried. A method for quantifying polymer and nucleic acid loss following spray drying was developed in order to ensure that equal nucleic acid amounts were used in all in vitro experiments. The results confirm that spray dried NEM formulations containing nucleic acids can be prepared with characteristics known to be optimal for inhalation therapy.


Assuntos
Nanopartículas/química , Ácidos Nucleicos/química , Polietilenoimina/química , Pós/química , Células A549 , Administração por Inalação , Aerossóis/química , Varredura Diferencial de Calorimetria/métodos , Linhagem Celular Tumoral , Química Farmacêutica/métodos , Dessecação/métodos , Excipientes/química , Humanos , Manitol/química , Microscopia Eletrônica de Varredura/métodos , Tamanho da Partícula , Trealose/química
16.
Eur J Pharm Biopharm ; 143: 80-90, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31446044

RESUMO

Retinoid acid (RA) and other retinoids are extensively used as therapeutic agents in the treatment of several types of cancer and skin disorders. However, the efficiency of these medical agents is compromised due to the unsatisfactory concentration of retinoids in the target cells/tissues. Furthermore, severe side-effects are related to retinoids administration. Incorporation of retinoids into carrier-based delivery systems using encapsulation technology has been proposed in order to overcome the limitations of using free retinoids in the treatment of several pathologies. The present work starts exploring the competences and the difficulties of using retinoids in health care. The metabolism and the main considerations about the mechanism of action of retinoids are also discussed. The final sections are focused on the most recent studies about RA controlled delivery systems to be used in the medical field.


Assuntos
Neoplasias/tratamento farmacológico , Retinoides/administração & dosagem , Retinoides/química , Dermatopatias/tratamento farmacológico , Animais , Química Farmacêutica/métodos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos
17.
AAPS PharmSciTech ; 20(7): 271, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363868

RESUMO

Dry powder inhalers have attracted more interest over the years in every aspect related to them. Interestingly, when focusing on the effects of particle morphology of the active or carrier (excipient), it is generally regarded particle size and shape to influence drug availability of aerosolized particles. However, to date, few studies have examined the effect of texture, i.e., roughness, on this relationship. The main objective of the present work is to gain a closer understanding of the influence of carrier morphology on the aerosolization performance of dry powder inhaler formulations. Image analysis and microscopy were used to visualize the aerosolization process. It is considered that the scale of morphological features on the surface of the carrier particles is responsible for the dispersion of the powder formulation, separation of the drug/carrier, and entrainment from a dry powder inhaler. Thus, for this study, the carrier particles of different surface roughness were mixed with micronized salbutamol sulphate. Aerosolization in vitro testing was used to evaluate the performance. The results indicate a connection between the qualitative surface roughness of coarse carriers and aerosolization performance during powder dispersibility. This investigation demonstrated that indeed, powder dispersion, a dynamic process, is influenced by the scale of the carrier morphology.


Assuntos
Albuterol/química , Albuterol/farmacocinética , Broncodilatadores/química , Broncodilatadores/farmacocinética , Química Farmacêutica/métodos , Inaladores de Pó Seco/métodos , Administração por Inalação , Aerossóis/química , Aerossóis/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Inaladores de Pó Seco/instrumentação , Excipientes/química , Excipientes/farmacocinética , Tamanho da Partícula , Pós , Propriedades de Superfície
18.
AAPS PharmSciTech ; 20(7): 273, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31385126

RESUMO

Orodispersible films (ODFs) are more convenient for paediatric and geriatric patients to take as compared to conventional tablets and capsules. Electrospinning has recently been attempted to produce ODFs. This study investigated the feasibility of formulating poorly water-soluble drug into ODFs using electrospinning technology coupled with the anti-solvent precipitation method. Piroxicam (PX), a poorly water-soluble drug, was chosen as a model drug. Polyvinyl alcohol and polyvinylpyrrolidone were used as film forming polymers. PX microcrystals were prepared using poloxamer as the stabilizer with the anti-solvent precipitation method, and then loaded in ODFs through the electrospinning process. The obtained ODFs were characterized using a scanning electron microscope, X-ray powder diffraction and Fourier transform infrared spectroscopy with respect to the morphology, solid state and potential molecular interaction between the model drug and polymers. The mechanical property, disintegration and dissolution rate of the obtained ODF were evaluated using dynamic mechanical analysis, a customized method and USP2 apparatus. The results showed that PX microcrystals suspended in polymeric solutions could be readily electrospun into fibrous films, where the microcrystals scattered between the fibers. The electrospun fibrous film-based ODFs exhibited satisfactory mechanical behaviour, and fast disintegration upon the polymer selection. In the dissolution tests, almost 90% of PX was dissolved within 6 min from the ODFs, whereas 40% of PX dissolved from physical mixtures in 60 min. This study demonstrated that poorly water-soluble drugs could be formulated into ODFs with satisfactory quality attributes by combining micronization and the electrospinning process.


Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Química Farmacêutica/métodos , Portadores de Fármacos/síntese química , Piroxicam/síntese química , Água/química , Administração Oral , Cristalização , Humanos , Polímeros/química , Álcool de Polivinil/química , Solubilidade , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Comprimidos , Difração de Raios X/métodos
19.
Eur J Pharm Biopharm ; 142: 531-539, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31362056

RESUMO

Antimicrobial resistance is one of the most serious problems that researchers of multiple disciplines are working on. The number of new antibiotics and their targeted structures have continuously decreased emphasizing the demand of alternative therapy for bacterial infections. Photodynamic therapy is such a promising strategy that has been proven to be effective against a wide range of bacterial strains. In this study, an inhalable nanoformulation for photodynamic therapy against respiratory infections was developed in the form of nano-in-microparticles consisting of curcumin nanoparticles embedded in a mannitol matrix. The produced nano-in-microparticles exhibited suitable aerodynamic properties with a mass median aerodynamic diameter of 2.88 ±â€¯0.13 µm and a high fine particle fraction of 60.99 ±â€¯9.50%. They could be readily redispersed in an aqueous medium producing the original nanoparticles without any substantial changes in their properties. This was confirmed using dynamic light scattering and electron microscopy. Furthermore, the redispersed nanoparticles showed an efficient antibacterial photoactivity causing 99.99992% (6.1log10) and 97.75% (1.6log10) reduction in the viability of Staphylococcus saprophyticus subsp. bovis and Escherichia coli DH5 alpha respectively. Based on these findings, it can be concluded that nano-in-microparticles represent promising drug delivery systems for antimicrobial photodynamic therapy.


Assuntos
Antibacterianos/química , Curcumina/química , Nanopartículas/química , Administração por Inalação , Antibacterianos/farmacologia , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Inaladores de Pó Seco/métodos , Escherichia coli/efeitos dos fármacos , Excipientes/química , Manitol/química , Tamanho da Partícula , Fotoquimioterapia/métodos , Pós/química , Staphylococcus saprophyticus/efeitos dos fármacos
20.
Nat Commun ; 10(1): 3061, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296858

RESUMO

The importance of axial chirality in enantioselective synthesis has been widely recognized for decades. The practical access to certain structures such as biaryl amino phenols known as NOBINs in enantiopure form, however, still remains a challenge. In drug delivery, the incorporation of axially chiral molecules in systematic screening has also received a great deal of interest in recent years, which calls for innovation and practical synthesis of structurally different axially chiral entities. Herein we present an operationally simple catalytic N-alkylation of sulfonamides using commercially available chiral amine catalysts to deliver two important classes of axially chiral compounds: structurally diverse NOBIN analogs as well as axially chiral N-aryl sulfonamides in excellent enantiopurity. Structurally related chiral sulfonamide has shown great potential in drug molecules but enantioselective synthesis of them has never been accomplished before. The practical catalytic procedures of our methods also bode well for their wide application in enantioselective synthesis.


Assuntos
Aminofenóis/síntese química , Sistemas de Liberação de Medicamentos , Sulfonamidas/síntese química , Alquilação , Catálise , Química Farmacêutica/métodos , Estrutura Molecular , Estereoisomerismo
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