RESUMEN
The increasing application of recombinant enzymes demands not only effective and sustainable fermentation, but also highly efficient downstream processing and further stabilization of the enzymes by immobilization. In this study, a novel approach for the isolation and immobilization of His-tagged transaminase from Chromobacterium violaceum (CvTA) has been developed. A recombinant of CvTA was simultaneously isolated and immobilized by binding on silica nanoparticles (SNPs) with metal affinity linkers and additionally within poly(lactic acid) (PLA) nanofibers. The linker length and the nature of the metal ion significantly affected the enzyme binding efficiency and biocatalytic activity of CvTA-SNPs. The formation of PLA nanofibers by electrospinning enabled rapid embedding of CvTA-SNPs biocatalysts and ensured enhanced stability and activity. The developed advanced immobilization method reduces the time required for enzyme isolation, purification and immobilization by more than fourfold compared to a classical stepwise technique.
Asunto(s)
Enzimas Inmovilizadas , Nanocompuestos , Enzimas Inmovilizadas/metabolismo , Transaminasas , Poliésteres , Lipasa , MetalesRESUMEN
Encapsulation possibilities of an extensively investigated neuroprotective drug (kynurenic acid, KYNA) are studied via lipid-based nanocarriers to increase the blood-brain barrier (BBB) specific permeability. The outcomes of various preparation conditions such as stirring and sonication time, concentration of the lipid carriers and the drug, and the drug-to-lipid ratio are examined. Considering the experimentally determined encapsulation efficiency, hydrodynamic diameter, and ζ-potential values, the initial lipid and drug concentration as well as the stirring and sonication time of the preparation were optimized. The average hydrodynamic diameter of the prepared asolectin-(LIP) and water-soluble lipopolymer (WSLP)-based liposomes was found to be ca. 25 and 60 nm under physiological conditions. The physicochemical characterization of the colloidal carriers proves that the preparation of the drug-loaded liposomes was a successful process, and secondary interactions were indicated between the drug molecule and the polymer residues around the WSLP membrane. Dissolution profiles of the active molecule under physiological conditions were registered, and the release of the unformulated and encapsulated drug is very similar. In addition to this outcome, the in vitro polar brain lipid extract (porcine)-based permeability test proved the achievement of two- or fourfold higher BBB specific penetration and lipid membrane retention for KYNA in the liposomal carriers relative to the unformatted drug.
Asunto(s)
Barrera Hematoencefálica , Ácido Quinurénico , Animales , Porcinos , Liposomas , Neuroprotección , EncéfaloRESUMEN
The current research is aimed at investigating the relationship between the formulation components and conditions in the case of a binary drug delivery system, where antidiabetic drugs are co-formulated into polymeric micelles embedded in sodium alginate. Compared to chemical modifications of polymers with alginate, our development provides a simpler and scalable formulation process. Our results prove that a multi-level factorial design-based approach can ensure the development of a value-added polymeric micelle formulation with an average micelle size of 123.6 ± 3.1 nm and a monodisperse size distribution, showing a polydispersity index value of 0.215 ± 0.021. The proper nanoparticles were co-formulated with sodium alginate as a biologically decomposing and safe-to-administer biopolymer. The Box-Behnken factorial design ensured proper design space development, where the optimal sodium alginate bead formulation had a uniform, extended-release drug release mechanism similar to commercially available tablet preparations. The main conclusion is that the rapid-burst-like drug release can be hindered via the embedment of nanocarriers into biopolymeric matrices. The thermally stable formulation also holds the benefit of uniform active substance distribution after freeze-drying.
Asunto(s)
Alginatos , Micelas , Alginatos/química , Sistemas de Liberación de Medicamentos/métodos , Preparaciones de Acción Retardada/química , Liberación de Fármacos , Polímeros , Tamaño de la PartículaRESUMEN
The brain insulin metabolism alteration has been addressed as a pathophysiological factor underlying Alzheimer's disease (AD). Insulin can be beneficial in AD, but its macro-polypeptide nature negatively influences the chances of reaching the brain. The intranasal (IN) administration of therapeutics in AD suggests improved brain-targeting. Solid lipid nanoparticles (SLNs) and poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are promising carriers to deliver the IN-administered insulin to the brain due to the enhancement of the drug permeability, which can even be improved by chitosan-coating. In the present study, uncoated and chitosan-coated insulin-loaded SLNs and PLGA NPs were formulated and characterized. The obtained NPs showed desirable physicochemical properties supporting IN applicability. The in vitro investigations revealed increased mucoadhesion, nasal diffusion, and drug release rate of both insulin-loaded nanocarriers over native insulin with the superiority of chitosan-coated SLNs. Cell-line studies on human nasal epithelial and brain endothelial cells proved the safety IN applicability of nanoparticles. Insulin-loaded nanoparticles showed improved insulin permeability through the nasal mucosa, which was promoted by chitosan-coating. However, native insulin exceeded the blood-brain barrier (BBB) permeation compared with nanoparticulate formulations. Encapsulating insulin into chitosan-coated NPs can be beneficial for ensuring structural stability, enhancing nasal absorption, followed by sustained drug release.
Asunto(s)
Encéfalo/citología , Quitosano/química , Insulina/farmacología , Nariz/citología , Encéfalo/metabolismo , Línea Celular , Liberación de Fármacos , Células Endoteliales/química , Células Endoteliales/citología , Insulina/química , Liposomas/química , Nanopartículas/química , Nariz/química , Tamaño de la Partícula , Ácido Poliglicólico/químicaRESUMEN
The present study aimed to develop n-propyl gallate (PG)-encapsulated liposomes through a novel direct pouring method using the quality-by-design (QbD) approach. A further aim was to coat liposomes with hyaluronic acid (HA) to improve the stability of the formulation in nasal mucosa. The QbD method was used for the determination of critical quality attributes in the formulation of PG-loaded liposomes coated with HA. The optimized formulation was determined by applying the Box-Behnken design to investigate the effect of composition and process variables on particle size, polydispersity index (PDI), and zeta potential. Physiochemical characterization, in vitro release, and permeability tests, as well as accelerated stability studies, were performed with the optimized liposomal formulation. The optimized formulation resulted in 90 ± 3.6% encapsulation efficiency, 167.9 ± 3.5 nm average hydrodynamic diameter, 0.129 ± 0.002 PDI, and -33.9 ± 4.5 zeta potential. Coated liposomes showed significantly improved properties in 24 h in an in vitro release test (>60%), in vitro permeability measurement (420 µg/cm2) within 60 min, and also in accelerated stability studies compared to uncoated liposomes. A hydrogen-peroxide-scavenging assay showed improved stability of PG-containing liposomes. It can be concluded that the optimization of PG-encapsulated liposomes coated with HA has great potential for targeting several brain diseases.
Asunto(s)
Antioxidantes/administración & dosificación , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Ácido Hialurónico/química , Liposomas/administración & dosificación , Galato de Propilo/administración & dosificación , Administración Intranasal , Animales , Antioxidantes/química , Liberación de Fármacos , Liposomas/química , Ratones , Galato de Propilo/químicaRESUMEN
PURPOSE: To design and stabilize Liraglutide loaded poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) proper for oral administration. METHODS: PLGA NPs were prepared by means of double emulsion solvent evaporation method and optimized by applying 7-factor 2-level Plackett-Burman screening design. RESULTS: Spherical shaped NPs with homogeneous distribution, 188.95 nm particle size and 51.81% encapsulation efficiency were obtained. Liraglutide was successfully entrapped in the NPs while maintaining its native amorphous nature, and its structural integrity as well. CONCLUSION: Lira-PLGA NPs with the required Critical Quality Attributes (CQAs) were successfully designed by implementing a 7-factor 8-run Plackett Burman design into the extended Quality by Design (QbD) model, to elucidate the effect of formulation and process variables on the particle size, size-distribution, encapsulation efficiency and surface charge. As the developed nanoparticles maintained the native structure of the active pharmaceutical ingredient (API), they are promising compositions for the further development for the oral delivery of Lira. Graphical Abstract.
Asunto(s)
Portadores de Fármacos/química , Hipoglucemiantes/química , Liraglutida/química , Nanopartículas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Administración Oral , Liberación de Fármacos , Emulsiones , Hipoglucemiantes/administración & dosificación , Liraglutida/administración & dosificación , Tamaño de la PartículaRESUMEN
A recommended first-line acute bacterial rhinosinusitis (ABR) treatment regimen includes a high dose of orally administered amoxicillin, despite its frequent systemic adverse reactions coupled with poor oral bioavailability. Therefore, to overcome these issues, nasal administration of amoxicillin might become a potential approach for treating ABR locally. The present study aimed to develop a suitable carrier system for improved local nasal delivery of amoxicillin employing the combination of albumin nanoparticles and gellan gum, an ionic-sensitive polymer, under the Quality by Design methodology framework. The application of albumin nanocarrier for local nasal antibiotic therapy means a novel approach by hindering the nasal absorption of the drug through embedding into an in situ gelling matrix, further prolonging the drug release in the nasal cavity. The developed formulations were characterized, including mucoadhesive properties, in vitro drug release and antibacterial activities. Based on the results, 0.3 % w/v gellan gum concentration was selected as the optimal in situ gelling matrix. Essentially, each formulation adequately inhibited the growth of five common nasal pathogens in ABR. In conclusion, the preparation of albumin-based nanoparticles integrated with in situ ionic-sensitive polymer provides promising ability as nanocarrier systems for delivering amoxicillin intranasally for local antibiotic therapy.
Asunto(s)
Amoxicilina , Nanopartículas , Albúmina Sérica Bovina , Administración Intranasal , Mucosa Nasal , Antibacterianos , Polímeros , Geles , Sistemas de Liberación de Medicamentos , Polisacáridos BacterianosRESUMEN
Ascorbic acid (AA) has a pivotal role in corneal wound healing via stimulating the biosynthesis of highly organized extracellular matrix components, but its rapid degradation and low corneal permeability limits its therapeutic effects. In this paper, we present the pharmacokinetic properties of a liposomal-based formulation of AA in terms of corneal permeation. Chemical stability, shelf-life, and drug release rate of lyophilized liposome (AA-LLipo) formulation was determined in comparison to free-form of AA solution using high-performance liquid chromatography (HPLC) and rapid equilibrium dialysis. In vitro transcorneal permeability was studied using a parallel artificial membrane permeability assay (PAMPA). Ex vivo permeation was examined on AA-LLipo-treated porcine cornea by determining the AA content on the ocular surface, in the cornea as well as in the aqueous humor using HPLC, and by Raman-mapping visualizing the AA-distribution. Our results showed that the liposomal formulation improved the chemical stability of AA, while drug release was observed with the same kinetic efficiency as from the free-form of AA solution. Both corneal-PAMPA and porcine corneal permeability studies showed that AA-LLipo markedly improved the corneal absorption kinetics of AA, thus, increasing the AA content in the cornea and aqueous humor. AA-LLipo formulation could potentially increase the bioavailability of AA in corneal tissues.
Asunto(s)
Lesiones de la Cornea , Liposomas , Animales , Porcinos , Córnea , Permeabilidad , Ácido AscórbicoRESUMEN
In our present series of experiments, we investigated the nasal applicability of the previously developed Soluplus® - meloxicam polymeric micelle formulation. Utilizing the nasal drug investigations, moderately high mucoadhesion was experienced in nasal conditions which alongside the appropriate physicochemical properties in liquid state, contributed to rapid drug absorption through human RPMI 2650 cell line. Ex vivo studies also confirmed that higher nasal mucosal permeation could be expected with the polymeric micelle nanoformulation compared to a regular MEL suspension. Also, the nanoformulation met the requirements to provide rapid drug permeation in less 1 h of our measurement. The non-toxic, non-cell barrier damaging formulation also proved to provide a successful passive transport across excides human nasal mucosa. Based on our in vivo investigations, it can be concluded that the polymeric micelle formulation provides higher meloxicam transport to the central nervous system followed by a slow and long-lasting elimination process compared to prior results where physical particle size reduction methods were applied. With these results, a promising solution and nanocarrier is proposed for the successful transport of non-steroidal anti-inflammatory drugs with acidic character to the brain.
Asunto(s)
Micelas , Mucosa Nasal , Humanos , Administración Intranasal , Meloxicam/metabolismo , Mucosa Nasal/metabolismo , Polímeros/química , Encéfalo/metabolismoRESUMEN
Current study aimed to develop a spray-dried powder containing indomethacin (IND)-loaded polymeric micelles which can be administered perorally as a dissolved powder to enhance the drug release and permeability of the active substance. The resulting low dense spray-dried spherical particles have decreased particle size (7.21 µm) in monodisperse distribution. The polymeric micelles had a nano size range (130 nm) also in monodisperse size distribution. These nanoparticulate properties and the high encapsulation efficiency (> 80%) lead to the improvement of gastrointestinal drug release in fasted and fed state conditions. Following second order and Higuchi kinetics, a rapid drug release was experienced exceeding the initial IND suspension. In vitro cell line studies on Caco-2 human colorectal adenocarcinoma cells showed that the formulation does not increase the toxicity of initial IND, therefore can be considered safe for oral application. Ex vivo semiquantitative and quantitative studies were performed on porcine small intestine where increased flux and permeability values of IND were achieved. The physical stability of the solid formulation was sufficient through a 6-month intermediate study caused by the hydrogen-bond formation between IND and the micelle-forming co-polymer.
Asunto(s)
Indometacina , Micelas , Animales , Células CACO-2 , Liberación de Fármacos , Humanos , Indometacina/química , Tamaño de la Partícula , Permeabilidad , Polímeros , Polvos , Solubilidad , PorcinosRESUMEN
Our present series of experiments was to create a value-added formulation that has the potential to exert a powerful and long-lasting antibacterial effect for use in ophthalmology. Erythromycin-loaded polymeric micelles were formulated with a micelle size of 87.14 nm in a monodisperse distribution with 86.94 % encapsulation efficiency. To decrease the polymeric micelle-like burst effect of these nanoparticles, the formulation was dispersed in a Carbopol 934P gel base to prolong the drug release and permeation profile of erythromycin. With successful incorporation, a short gelling time with proper sol to gel transition was experienced in the form of transparent gels. The optimized formulation has high mucoadhesion which is a critical factor for prolonging residence time. With the initial burst, the drug release was saturated with more than 75 % of the drug released in simulated tear fluid. Corneal permeability investigations revealed that the gel formulation provides the value-added properties of polymeric micelles, with elevated permeability through into the aqueous humour across the cornea. While retaining its antimicrobial activity, the formulation may be capable to be utilized as an innovative ophthalmic formulation for treating bacterial infections of the eye.
Asunto(s)
Eritromicina , Micelas , Eritromicina/farmacología , Geles/farmacología , Polímeros/farmacología , Córnea , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/farmacologíaRESUMEN
The therapeutic application of nasal powders requires the development of novel mucoadhesive excipients. Thiolated polymers exhibit significant potential for this purpose based on their increased mucoadhesion attributable to the formation of disulfide bonds between the polymer and mucus surface. A chitosan-cysteine (chit-cyst) conjugate was synthesized using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide in aqueous solution. The synthetic yield and synthesis conditions were optimized, and the efficiency of the reaction was evaluated. Rheological measurements revealed that the polymer derivative exhibited increased mucoadhesive properties in comparison to chitosan powder. To characterize the polymer, a novel purity investigation method was developed and verified to investigate the residual l-cysteine content. The results revealed that l-cysteine was not detectable in the resultant polymer matrix. Based on the cytotoxicity studies, chit-cyst was found to be safe for nasal application. Thereafter, nasal powder formulations were prepared using the polymer and the antiparkinsonian drug levodopa methyl ester hydrochloride by freeze-drying to investigate their nasal applicability. Based on the in vitro studies, these powders might be suitable for reducing the off periods of Parkinson's disease because of their expected higher in vivo mucoadhesion.
Asunto(s)
Quitosano , Quistes , Antiparkinsonianos , Cisteína/química , Disulfuros/química , Excipientes/química , Humanos , Polímeros/química , Polvos , Compuestos de Sulfhidrilo/químicaRESUMEN
Our study aimed to formulate a novel dexamethasone (DXM)-loaded, mixed polymeric micelle-based drug delivery system, focusing on the auspicious nose-to-brain pathway, as a key delivery route to treat central nervous system (CNS) associated diseases. Polymeric micelles might be a solution to deliver drugs to the place of action compared to conventional formulations. Due to low Z-average (89.92 ± 2.7 nm), a polydispersity index of 0.216 ± 0.014 and high surface polarity (52.23%), a significant increase in water solubility (14-fold) was experienced. This increase resulted in favourable dissolution profile at nasal and axonal conditions with high in vitro permeability value (14.6×10-6 cm/s) on polar brain (porcine) lipid extract. Modified Side-bi-side® type diffusion study confirmed rapid and efficient passive diffusion through the nasal mucosa contributed by strong mucoadhesive properties. The final formulation met all the requirements of a nasal drug delivery system with rapid onset of action, meaning DXM can reach the CNS and there it can exert its beneficial effects in pathological conditions.
Asunto(s)
Portadores de Fármacos , Micelas , Animales , Dexametasona , Sistemas de Liberación de Medicamentos , Tamaño de la Partícula , Polímeros , Solubilidad , PorcinosRESUMEN
The aim of this study was to investigate whether and how the biological media which are in contact with silicone oil play a role in the silicone emulsification process. Commercially available Oxane 1300 silicone oil and potential hydrophilic phases of the emulsions in the eye (porcine aqueous humor, porcine vitreous and balanced salt solution) were investigated separately and in a mixture or emulsions by means of surface tension, rheological, zeta potential measurements and microscopic investigation. The surface tension of biological media (vitreous and aqueous humor) was significantly lower than that of non-biological media, especially in the case of aqueous humor, which indicates a remarkable emulsification tendency with these phases. The biological media are able to form both oil-in-water and water-in-oil emulsions, which can be observed in the clinical practice as well. It was established that the vitreous has a more expressed emulsification ability compared with the aqueous humor because smaller and more stable droplets can form with silicon oil when the vitreous is still there. It can be concluded that the vitreous has a higher impact on emulsification than the aqueous medium, which can predict that the vitreous remaining after vitrectomy has a key role in emulsion formation in the eye with silicone oil endotamponade.
Asunto(s)
Humor Acuoso/química , Soluciones Isotónicas/química , Aceites de Silicona/química , Cuerpo Vítreo/química , Animales , Emulsiones , Reología , Tensión Superficial , Porcinos , Vitrectomía/métodosRESUMEN
Levodopa (LEVO) as the gold standard in the treatment of Parkinson's disease is usually administrated per os but its bioavailability is low. The intranasal administration is a potential alternative route to increase bioavailability of the drug and treat the off period. Our aim was to develop LEVO-containing binary nasal powders with different excipients by dry cogrinding process. The interactions between the components were examined. The optimized cogrinding process parameters (LEVO:excipient ratio and grinding time) resulted in the desired particle size range (5-40 µm). The α-cyclodextrin and poly(vinylpyrrolidone) (PVP) had an intensive crystallinity degree reducing effect on LEVO measured by XRPD, and they functioned as cogrinding agents. Hydroxypropyl methylcellulose, poly (vinyl alcohol) (PVA), and D-mannitol associate around the LEVO crystals preventing its crystalline structure. Hydrogen bonding was detected only for LEVO-PVP and LEVO-D-mannitol used Fourier-transformed infrared spectroscopy. Chemical degradation of LEVO in the products was not detected even after the accelerated stability test. The dissolution profile of the products can be characterized by the first-order kinetic model with different dissolution rate. The dissolution rate of LEVO was increased with α-cyclodextrin and PVP, and the drug release decreased in the case of hydroxypropyl methylcellulose, PVA, and D-mannitol compared to the LEVO powder.
Asunto(s)
Antiparkinsonianos/química , Excipientes/química , Levodopa/química , Administración Intranasal , Antiparkinsonianos/administración & dosificación , Cristalización , Composición de Medicamentos , Liberación de Fármacos , Excipientes/administración & dosificación , Derivados de la Hipromelosa/administración & dosificación , Derivados de la Hipromelosa/química , Levodopa/administración & dosificación , Manitol/administración & dosificación , Manitol/química , Povidona/administración & dosificación , Povidona/química , Solubilidad , alfa-Ciclodextrinas/administración & dosificación , alfa-Ciclodextrinas/químicaRESUMEN
PURPOSE: The aim of this work was to study the influence of solidification of meloxicam (Mel) containing nanosuspension (nanoMel) on the physical stability and drug bioavailability of the products. The nanoMel sample had poly(vinyl alcohol) (PVA) as a protective polymer, but no surfactant as a further stabilizing agent because the final aim was to produce surfactant-free solid phase products as well. METHODS: The solidified samples produced by fluidization and lyophilization (fluidMel, lyoMel) were examined for particle size, crystallinity, and in vitro release of Mel compared to similar parameters of nanoMel. The products were subjected to an animal experiment using per oral administration to verify their bioavailability. RESULTS: Mel containing (1%) nanoMel sample was produced by wet milling process using an optimized amount of PVA (0.5%) which resulted in 130 nm as mean particle size and a significant reduction in the degree of crystallinity (13.43%) of Mel. The fluidization technique using microcrystalline cellulose (MCC) as carrier resulted in a quick conversion and no significant change in the critical product parameters. The process of lyophilization required a longer operation time, which resulted in the amorphization of the crystalline carrier (trehalose) and the recrystallization of Mel increased its particle size and crystallinity. The fluidMel and lyoMel samples had nearly five-fold higher relative bioavailability than nanoMel application by oral administration. The correlation between in vitro and in vivo studies showed that the fixed Mel nanoparticles on the surface of solid carriers (MCC, trehalose) in both the artificial gastric juice and the stomach of the animals rapidly reached saturation concentration leading to faster dissolution and rapid absorption. CONCLUSION: The solidification of the nanosuspension not only increased the stability of the Mel nanoparticles but also allowed the preparation of surfactant-free compositions with excellent bioavailability which may be an important consideration for certain groups of patients to achieve rapid analgesia.
Asunto(s)
Analgesia , Antiinflamatorios no Esteroideos/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Meloxicam/uso terapéutico , Nanopartículas/química , Dolor/tratamiento farmacológico , Administración Oral , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Disponibilidad Biológica , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/química , Liberación de Fármacos , Estabilidad de Medicamentos , Humanos , Meloxicam/administración & dosificación , Meloxicam/química , Tamaño de la Partícula , Alcohol Polivinílico/química , Propiedades de Superficie , Suspensiones/químicaRESUMEN
PURPOSE: The article reports a wet milling process, where the planetary ball mill was combined with pearl milling technology to reach nanosize range of meloxicam (Mel; 100-500 nm). The main purpose was to increase the dissolution rate and extent of a poorly water-soluble Mel as nonsteroidal anti-inflammatory drug as well as to study its permeability across cultured intestinal epithelial cell layers. METHODS: Viscosity of milled dispersion and particle size distribution and zeta potential of Mel were investigated and differential scanning calorimeter and X-ray powder diffractometer were used to analyse the structure of the suspended Mel. Finally in vitro dissolution test and in vitro cell culture studies were made. RESULTS: It was found that the ratio of predispersion and pearls 1:1 (w/w) resulted in the most effective grinding system (200-fold particle size reduction in one step) with optimized process parameters, 437 rpm and 43 min. Nanosuspension (1% Mel and 0.5% poly[vinyl alcohol]) as an intermediate product showed a stable system with 2 weeks of holding time. This optimized nanosuspension enhanced the penetration of Mel across cultured intestinal epithelial cell layers without toxic effects. CONCLUSION: The dissolution rate of Mel from the poly(vinyl alcohol) stabilized nanosuspension justified its applicability in the design of innovative per oral dosage form (capsule) in order to ensure/give a rapid analgesia.
Asunto(s)
Alcohol Polivinílico/química , Tecnología Farmacéutica , Tiazinas/química , Tiazoles/química , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Cristalización , Estabilidad de Medicamentos , Humanos , Meloxicam , Nanoestructuras , Tamaño de la Partícula , Solubilidad , Espectrometría Raman , Suspensiones , Tiazinas/análisis , Tiazinas/farmacología , Tiazoles/análisis , Tiazoles/farmacología , ViscosidadRESUMEN
The nasal delivery of drugs offers a great alternative route to avoid adverse events and to increase patient compliance due to its advantageous properties. Besides nasal application, topical, systemic and central effects are also available. Nasal powders (NPs) have better adhesion due to the additive polymers that may be, eg, gelling or good wettability agents; thus, their bioavailability is better compared to the liquid formulations. Using nanoparticles, innovative and more efficient products can be achieved, which may lead to the improvement of different therapies. The aim of this study was to produce NP formulations containing lamotrigine (LAM) as interactive physical mixtures and nanosized LAM-based formulations. After risk assessment of the preliminary tests, the micrometric properties (particle size and morphology) and the structural properties (differential scanning calorimetry [DSC], X-ray powder diffraction [XRPD]) were investigated; thereafter, physicochemical properties (solubility, polarity) and in vitro dissolution and diffusion profiles were also examined. These product samples showed an appropriate particle size ranging 10-25 µm, while the particle size of LAM in the products was between 120 and 230 nm and the dissolved amount of drug was >60% after 5 minutes in these cases.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Sistemas de Liberación de Medicamentos , Nanopartículas , Triazinas/administración & dosificación , Administración Intranasal , Rastreo Diferencial de Calorimetría , Química Farmacéutica/métodos , Composición de Medicamentos/métodos , Lamotrigina , Tamaño de la Partícula , Polímeros/química , Polvos , Solubilidad , Triazinas/química , Difracción de Rayos XRESUMEN
The focus of this research was to apply the in situ coating technology for producing paracetamol- (PCT-) containing pastilles for paediatric use from a eutectic of two sugar alcohols (sorbitol, xylitol) in one step. This type of melt-technology is more cost-efficient and simpler than other conventional tableting technologies, whereby the formation of the pastilles and their coating occur upon the same fabrication step. We managed to produce pastilles having a softer core and a harder, resistant shell in one cooling step. Adding polyethylene glycol (PEG) 2000 or 6000 to the PCT-containing eutectic, the dissolution rate of PCT could be considerably increased, especially when using PEG 2000, reaching equal dissolution characteristics both under mouth- and gastric-specific conditions. Distributions of the components within the pastilles have been determined by X-ray scattering and Raman spectroscopy. Physico-chemical parameters of the xylitol-sorbitol eutectic and their changes upon adding PCT and PEGs have been determined, and it has been revealed that xylitol and sorbitol form a new entity with a distinguished crystal structure. The significant changes in viscosity were explained and the interaction in the eutectic mixture was investigated using Fourier transform infrared spectroscopy (FT-IR). The uniformity of the physical parameters of the pastilles (including size, weight and drug content) also demonstrates the feasibility of using the cost-efficient and simple one-step eutectic-cooling technology for manufacturing pastilles.
Asunto(s)
Acetaminofén/síntesis química , Alcoholes del Azúcar/síntesis química , Tecnología Farmacéutica/métodos , Acetaminofén/farmacocinética , Química Farmacéutica , Solubilidad , Alcoholes del Azúcar/farmacocinética , Comprimidos Recubiertos , Difracción de Rayos X/métodosRESUMEN
OBJECTIVES/HYPOTHESIS: From an acoustic aspect, fixation of the medial end of an ossicular replacement prosthesis to the stapedial footplate would be desirable. Technically, ionomer cement seems an ideal material for this purpose. The objective was to determine the aluminum level of the perilymph after the application of ionomer cement on the stapedial footplate. STUDY DESIGN: An experimental study on rabbits. METHODS: A total of 25 Pannon White rabbits were divided into three groups. Five rabbits (group I) underwent sham operation; in 15 animals (group II) ionomer cement was applied onto the stapedial footplate; and in 5 cases (group III) the application of the cement onto the footplate was followed by opening of the vestibulum. In groups of 5, the animals were killed on day 1, 7, 30, 180, or 365 postoperatively. Fluid samples were taken from the vestibulum and their aluminum levels were determined. RESULTS: The average aluminum level in the fluid was insignificantly lower in group II than in group I, but significantly lower in groups I and II than in group III. CONCLUSION: As a glue, ionomer cement safely can be applied directly onto the footplate without the threat of raising the perilymphatic aluminum level, provided that there is no perilymph leakage. However, in the event of an open vestibulum, the application of cement onto the footplate is to be strongly discouraged due to the danger of a consequent increase in the aluminum level in the perilymph and the cerebrospinal fluid. LEVEL OF EVIDENCE: NA.