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1.
Anal Chem ; 92(14): 9730-9738, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32544319

RESUMO

Salt formation is a well-established method to increase the solubility of ionizable drug candidates. However, possible conversion of salt to its original form of free acid or base-disproportionation-can have a drastic effect on the solubility and consequently the bioavailability of a drug. Therefore, during the salt selection process, the salt dissolution behavior should be well understood. Improved understanding could be achieved by a method that enables simultaneous screening of small sample amounts and detailed dissolution process analysis. Here, we use a machine-vision-based single-particle analysis (SPA) method to successfully determine the pH-solubility profile, intrinsic solubility, common-ion effect, pKa, pHmax, and Ksp values of three model compounds in a fast and low sample consumption (<1 mg) manner. Moreover, the SPA method enables, with a particle-scale resolution, in situ observation of the disproportionation process and its immediate effect on the morphology and solubility of dissolving species. In this study, a potentially higher energy thermodynamic solid-state form of diclofenac free acid and an intriguing conversion to liquid verapamil free base were observed upon disproportionation of the respective salts. As such, the SPA method offers a low sample consumption platform for fast yet elaborate characterization of the salt dissolution behavior.

2.
Int J Pharm ; 581: 119280, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32229285

RESUMO

Powder flowability plays an important role in die filling during tablet manufacturing. The present study introduces a novel small-scale measuring technique for powder flow. Based on image analysis, the flow was defined depending on the variation of luminous intensity and the movement of powder inside the measurement cuvette. Using quantities around 100 mg it was possible to characterize a wide range of common pharmaceutical powders, especially in distinguishing subtle differences in flow caused by minor changes in samples characteristics. The method was compared with powder rheometry, which is widely used in the pharmaceutical literature, and showed a significant improvement in predicting the success of pharmaceutical minitablet manufacture (d = 5 mm). Tablet weight variation (RSD) was defined as the most efficient way to assess relevant powder flow behaviour in tablet production when using the novel device. The proposed method was distinguished from others by its ability to classify different grades of microcrystalline cellulose in the die-filling process. Subsequently, eight common pharmaceutical powders, both excipients and APIs, were properly ranked as a function of flowability based on their physical properties. The method showed a high repeatability, with a relative standard deviation not more than 10%.

3.
Anal Chem ; 91(11): 7411-7417, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31050887

RESUMO

Amorphous materials exhibit distinct physicochemical properties compared to their respective crystalline counterparts. One of these properties, the increased solubility of amorphous materials, is exploited in the pharmaceutical industry as a way of increasing bioavailability of poorly water-soluble drugs. Despite the increasing interest in drug amorphization, the analytical physicochemical toolbox is lacking a reliable method for direct amorphous solubility assessment. Here, we show, for the first time, a direct approach to measure the amorphous solubility of diverse drugs by combining optics with fluidics, the single particle analysis (SPA) method. Moreover, a comparison was made to a theoretical estimation based on thermal analysis and to a standardized supersaturation and precipitation method. We have found a good level of agreement between the three methods. Importantly, the SPA method allowed for the first experimental measurement of the amorphous solubility for griseofulvin, a fast crystallizing drug, without the use of a crystallization inhibitor. In conclusion, the SPA approach enables rapid and straightforward determination of the supersaturation potential for amorphous materials of less than 0.1 mg, which could prove highly beneficial in the fields of materials science, analytical chemistry, physical chemistry, food science, pharmaceutical science, and others.

4.
Int J Pharm ; 566: 194-202, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31100384

RESUMO

In the present study, a model was developed to estimate tablet tensile strength utilizing the gravitation-based high-velocity (G-HVC) method introduced earlier. Three different formulations consisting of microcrystalline cellulose (MCC), dicalcium phosphate dihydrate (DCP), hydroxypropyl methylcellulose (HPMC), theophylline and magnesium stearate were prepared. The formulations were granulated using fluid bed granulation and the granules were compacted with the G-HVC method and an eccentric tableting machine. Compaction energy values defined from G-HVC data predicted tensile strength of the tablets surprisingly well. It was also shown, that fluid bed granulation improved the compaction energy intake of the granules in comparison to respective physical mixtures. In addition, general mechanical properties and elastic recovery were also examined for all samples. In this study it was finally concluded, that the data obtained by the method was of practical relevance in pharmaceutical formulation development.


Assuntos
Comprimidos/química , Resistência à Tração , Fosfatos de Cálcio , Celulose , Gravitação , Derivados da Hipromelose , Modelos Teóricos , Tamanho da Partícula , Ácidos Esteáricos , Teofilina
5.
Anal Chem ; 91(6): 3997-4003, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30784269

RESUMO

Solubility is a physicochemical property highly dependent on the solid-state form of a compound. Thus, alteration of a compound's solid-state form can be undertaken to enhance the solubility of poorly soluble drug compounds. In the Biopharmaceutics Classification System (BCS), drugs are classified on the basis of their aqueous solubility and permeability. However, aqueous solubility does not always correlate best with in vivo solubility and consequently bioavailability. Therefore, the use of biorelevant media is a more suitable approach for mimicking in vivo conditions. Here, assessed with a novel image-based single-particle-analysis (SPA) method, we report a constant ratio of solubility increase of 3.3 ± 0.5 between the α and γ solid-state forms of indomethacin in biorelevant media. The ratio was independent of pH, ionic strength, and surfactant concentration, which all change as the drug passes through the gastrointestinal tract. On the basis of the solubility ratio, a free-energy difference between the two polymorphic forms of 2.9 kJ/mol was estimated. Lastly, the use of the SPA approach to assess solubility has proven to be simple, fast, and both solvent- and sample-sparing, making it an attractive tool for drug development.

6.
Eur J Pharm Sci ; 121: 260-268, 2018 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-29883725

RESUMO

The present study introduces a modified melt-electrospinning (MES) method for fabricating the melt-electrospun fibers (MSFs) of a poorly water-soluble drug and carrier polymer. The MES of poorly water-soluble model drug indomethacin (IND) and hydrophilic carrier polymer, Soluplus® (SOL) were prepared at a 1:3 drug-polymer weight ratio. Water was used as an external plasticizer to regulate a MES processing temperature and to improve fiber formation. The fiber size, surface morphology, physical solid state, drug-polymer (carrier) interactions, thermal and chemical stability and dissolution behavior of MSFs were investigated. Solid state nuclear magnetic resonance spectroscopy (NMR) was used to measure T1(1H), and the domain size of IND in MSFs (25-100 nm) was calculated from these results. Solid-state and thermal analysis confirmed the presence of amorphous solid dispersions of IND and SOL. IND was found to be chemically stable during an entire MES process. Only small drug content variability of different MSF batches was detected with high performace liquid chromatography (HPLC). Given findings were verified with the liquid NMR spectroscopy. The dissolution of MSFs was significantly faster than that of physical mixtures (PMs) or pure drug. The enhanced dissolution of MSFs was caused by high surface area, amorphous state of the drug and solubilizing properties of the carrier polymer (SOL).


Assuntos
Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Indometacina/química , Polietilenoglicóis/química , Polivinil/química , Solubilidade , Água/química
7.
Anal Chem ; 90(7): 4832-4839, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29513001

RESUMO

Raman spectroscopy is widely used for quantitative pharmaceutical analysis, but a common obstacle to its use is sample fluorescence masking the Raman signal. Time-gating provides an instrument-based method for rejecting fluorescence through temporal resolution of the spectral signal and allows Raman spectra of fluorescent materials to be obtained. An additional practical advantage is that analysis is possible in ambient lighting. This study assesses the efficacy of time-gated Raman spectroscopy for the quantitative measurement of fluorescent pharmaceuticals. Time-gated Raman spectroscopy with a 128 × (2) × 4 CMOS SPAD detector was applied for quantitative analysis of ternary mixtures of solid-state forms of the model drug, piroxicam (PRX). Partial least-squares (PLS) regression allowed quantification, with Raman-active time domain selection (based on visual inspection) improving performance. Model performance was further improved by using kernel-based regularized least-squares (RLS) regression with greedy feature selection in which the data use in both the Raman shift and time dimensions was statistically optimized. Overall, time-gated Raman spectroscopy, especially with optimized data analysis in both the spectral and time dimensions, shows potential for sensitive and relatively routine quantitative analysis of photoluminescent pharmaceuticals during drug development and manufacturing.


Assuntos
Corantes Fluorescentes/análise , Preparações Farmacêuticas/análise , Análise dos Mínimos Quadrados , Análise Espectral Raman , Fatores de Tempo
8.
Int J Pharm ; 539(1-2): 131-138, 2018 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-29414122

RESUMO

The compression physics of powders must be considered when developing a suitable tablet formulation. In the present study, the gravitation-based high-velocity method was utilized to analyze mechanical properties of eight common pharmaceutical excipients: two grades of lactose, anhydrous glucose, anhydrous calcium hydrogen phosphate, three grades of microcrystalline cellulose and starch. Samples were compressed five times consecutively with varying pressure and speed so that Setup A produced higher pressure and longer contact time than Setup B. The important parameters obtained from samples were porosity profiles, compaction pressure, contact time, internal energy change and the amount of elastic recovery. All acquired data was only based on distance-time profile of the compression event. Lactose and glucose fragmented effectively while calcium hydrogen phosphate remained in rearrangement phase, due to its hardness and insufficient pressure applied. Microcrystalline cellulose samples showed plastic behaviour and starch was most elastic of all the samples. By utilizing the method, examined excipients could be categorized according to their compression behaviour in an accurate and cost-efficient manner.


Assuntos
Composição de Medicamentos/métodos , Excipientes/química , Gravitação , Comprimidos/química , Força Compressiva , Pressão
9.
Int J Pharm ; 541(1-2): 188-197, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29481945

RESUMO

Solid dispersions (SDs) hold a proven potential in formulating poorly water-soluble drugs. The present paper investigates the interfacial phenomena associated with the bulk powder flow, water sorption, wetting and dissolution of the SDs prepared by a modified melt and quench-cooling (QC) method. Poorly water-soluble indomethacin (IND) was QC molten with solubilizing graft copolymer (Soluplus®) or polyol sugar alcohol (xylitol, XYL). The interfacial interactions of SDs with air/water were found to be reliant on the type (amorphous/crystalline) and amount of the carrier material used. The final SDs were composed of fused agglomerates (SOL) or large jagged particles (XYL) with good wetting and powder flow properties. The initial dissolution of IND was accelerated by both carrier materials studied. The QC molten SDs with amorphous Soluplus® significantly improved the dissolution rate of IND at pH 6.8 (79.9 ±â€¯0.2% at 30 min) compared to that of pure crystalline drug. The substantial improvement in the dissolution rate of IND was in connection with the amorphous state of the drug being stabilized by Soluplus® in the QC molten SDs. However, it is evident that a strong H-bond formation between the components in some regions of the QC molten SDs can limit the dissolution of IND. The QC molten two-phase SDs with a polyol carrier (XYL) showed rapid and continuous drug release without reaching a plateau.


Assuntos
Portadores de Fármacos/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Indometacina/farmacocinética , Química Farmacêutica , Estabilidade de Medicamentos , Excipientes/química , Indometacina/química , Transição de Fase , Polietilenoglicóis/química , Polivinil/química , Pós , Solubilidade , Xilitol/química
10.
Int J Pharm ; 544(2): 433-442, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29129573

RESUMO

The goal of this work was to study the printability of PDMS with a semi-solid extrusion printer in combination with the UV-assisted crosslinking technology using UV-LED light to manufacture drug containing structures. Structures with different pore sizes and different drug loadings were prepared containing prednisolone as a model drug. The work showed that it was possible to print drug-free and drug-loaded drug delivery devices of PDMS with the 3D printing technique used in this study. The required UV-curing time to get sufficient crosslinking yield and mechanical strength was minimum three minutes. The microgram drug release from the printed structures was highest for the most drug loaded structures regardless of the porosity of the devices. By altering the surface area/volume ratio it was possible to print structures with differences in the release rate. This study shows that room-temperature semi-solid extrusion printing 3D printing technique in combination with UV-LED crosslinking is an applicable method in the production of prednisolone containing PDMS devices. Both the extrusion 3D printing and the UV-crosslinking was done at room temperature, which make this manufacturing method an interesting alternative for manufacturing controlled release devices containing temperature susceptible drugs.


Assuntos
Preparações de Ação Retardada/química , Dimetilpolisiloxanos/química , Sistemas de Liberação de Medicamentos/métodos , Impressão Tridimensional , Tecnologia Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/instrumentação , Liberação Controlada de Fármacos , Estudos de Viabilidade , Porosidade , Temperatura , Raios Ultravioleta
11.
Expert Rev Med Devices ; 14(9): 685-696, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28774216

RESUMO

INTRODUCTION: The technological advancements in the pharmaceutical field are constantly improving and provide various possibilities for meeting the needs of personalized drug therapy. The three-dimensional (3D) printing technology has endless potential in the fabrication of patient-specific drug delivery devices (DDD) and dosage forms as the technological development is progressing. Moreover, the rapidly evolving research on 3D printed DDD has enabled us to determine several challenges related to the manufacturing and marketing of personalized drug delivery systems. Areas covered: In this review, an overview is provided on the relevant accomplishments in the development of 3D printed drug delivery systems, as well as the technical challenges surrounding the 3D printing of personalized drug-loaded medical devices and dosage forms. Furthermore, observations are presented on the future perspectives of pharmaceutical 3D printing. Expert commentary: The 3D printing has enabled the fabrication of prototypes of DDD with varying complexity and shows that customization of drug products is possible. There is potential to improve patient-specific drug therapies of the future using printing technologies. The technological advancements, new scientific concepts, interdisciplinary work and defined regulatory guidelines will continue to support and strengthen the prospects of 3D printing as an option in the manufacture of medical products.


Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Preparações Farmacêuticas/administração & dosagem , Impressão Tridimensional , Humanos , Medicina de Precisão , Tecnologia Farmacêutica/tendências
12.
J Pharm Biomed Anal ; 145: 549-554, 2017 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-28759863

RESUMO

We introduce a system with a lyophilic matrix to aid dissolution studies of powders and particulate systems. This lyophilic matrix method (LM method) is based on the ability to discriminate between non-dissolved particles and the dissolved species. In the LM method the test substance is embedded in a thin lyophilic core-shell matrix. This permits rapid contact with the dissolution medium while minimizing dispersion of non-dissolved particles without presenting a substantial diffusion barrier. The method produces realistic dissolution and release results for particulate systems, especially those featuring nanoscale particles. By minimizing method-induced effects on the dissolution profile of nanopowders, the LM method overcomes shortcomings associated with current dissolution tests.


Assuntos
Nanopartículas , Difusão , Pós , Solubilidade
13.
AAPS PharmSciTech ; 18(8): 3198-3207, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28540484

RESUMO

A new dry granulation technique, gas-assisted roller compaction (GARC), was compared with conventional roller compaction (CRC) by manufacturing 34 granulation batches. The process variables studied were roll pressure, roll speed, and sieve size of the conical mill. The main quality attributes measured were granule size and flow characteristics. Within granulations also the real applicability of two particle size analysis techniques, sieve analysis (SA) and fast imaging technique (Flashsizer, FS), was tested. All granules obtained were acceptable. In general, the particle size of GARC granules was slightly larger than that of CRC granules. In addition, the GARC granules had better flowability. For example, the tablet weight variation of GARC granules was close to 2%, indicating good flowing and packing characteristics. The comparison of the two particle size analysis techniques showed that SA was more accurate in determining wide and bimodal size distributions while FS showed narrower and mono-modal distributions. However, both techniques gave good estimates for mean granule sizes. Overall, SA was a time-consuming but accurate technique that provided reliable information for the entire granule size distribution. By contrast, FS oversimplified the shape of the size distribution, but nevertheless yielded acceptable estimates for mean particle size. In general, FS was two to three orders of magnitude faster than SA.


Assuntos
Celulose/síntese química , Tamanho da Partícula , Tecnologia Farmacêutica/métodos , Composição de Medicamentos/métodos , Pós , Pressão , Comprimidos
14.
Int J Pharm ; 526(1-2): 31-40, 2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28434934

RESUMO

With modern tableting machines large amounts of tablets are produced with high output. Consequently, methods to examine powder compression in a high-velocity setting are in demand. In the present study, a novel gravitation-based method was developed to examine powder compression. A steel bar is dropped on a punch to compress microcrystalline cellulose and starch samples inside the die. The distance of the bar is being read by a high-accuracy laser displacement sensor which provides a reliable distance-time plot for the bar movement. In-die height and density of the compact can be seen directly from this data, which can be examined further to obtain information on velocity, acceleration and energy distribution during compression. The energy consumed in compact formation could also be seen. Despite the high vertical compression speed, the method was proven to be cost-efficient, accurate and reproducible.


Assuntos
Gravitação , Pós , Tecnologia Farmacêutica , Celulose , Pressão , Comprimidos
15.
J Nat Prod ; 80(4): 916-924, 2017 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-28333461

RESUMO

The isolation and physical material properties of suberin fatty acids (SFAs) were investigated with special reference to their potential applications as novel pharmaceutical excipients. SFAs were isolated from outer birch bark (OBB) with a new extractive hydrolysis method. The present simplified isolation process resulted in a moderate batch yield and chemical purity of SFAs, but further development is needed for establishing batch-to-batch variation. Cryogenic milling was the method of choice for the particle size reduction of SFAs powder. The cryogenically milled SFAs powder exhibited a semicrystalline structure with apparent microcrystalline domains within an amorphous fatty acids matrix. The thermogravimetric analysis (TGA) of SFAs samples showed a good thermal stability up to 200 °C, followed by a progressive weight loss, reaching a plateau at about 95% volatilization at about 470 °C. The binary blends of SFAs and microcrystalline cellulose (MCC; Avicel PH 101) in a ratio of 25:75 (w/w) displayed good powder flow and tablet compression properties. The corresponding theophylline-containing tablets showed sustained or prolonged-release characteristics. The physicochemical and bulk powder properties of SFAs isolated from OBB are auspicious in terms of potential pharmaceutical excipient applications.


Assuntos
Betula/química , Ácidos Graxos/isolamento & purificação , Lipídeos/isolamento & purificação , Lipídeos/farmacologia , Casca de Planta/química , Celulose , Química Farmacêutica , Excipientes/farmacologia , Ácidos Graxos/química , Lipídeos/química , Estrutura Molecular , Comprimidos/farmacologia , Teofilina/análise
16.
Eur J Pharm Sci ; 97: 237-246, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27890595

RESUMO

Amorphous solid dispersions (SDs) are a promising approach to improve the dissolution rate of and oral bioavailability of poorly water-soluble drugs. In some cases multi-phase, instead of single-phase, SD systems with amorphous drug are obtained. While it is widely assumed that one-phase amorphous systems are desirable, two-phase systems may still potentially exhibit enhanced stability and dissolution advantages over undispersed systems. The objective of the present study was to understand the solid-state properties of two-phase SDs with amorphous drug and their relation to physical stability. Two different types of excipients for SD formation were used, one being a polymer and the other a small molecule excipient. The supercooled molten SDs of a poorly water-soluble indomethacin (IND) with a graft copolymer, Soluplus® (SOL) and sugar alcohol, xylitol (XYL) were prepared. Supercooled molten SDs of IND with SOL were two-phase glassy suspension in which the amorphous drug was dispersed in an amorphous polymer matrix. A short-term aging of the SDs led to the formation of glassy suspensions where the crystalline drug was dispersed in an amorphous polymer matrix. These were physically stable at room temperature for the time period studied (RT, 23±2°C), but aging at high-humidity conditions (75% RH) recrystallization to metastable α-IND occurred. Interestingly, the SDs with XYL were two-phase amorphous precipitation systems in which the drug was in an amorphous form in the crystalline sugar alcohol matrix. The SDs of IND and XYL exhibited fast drug recrystallization. In conclusion, the preparation method of two-phase systems via co-melting in association with the rapid quench cooling is a feasible method for the formulation of poorly water-soluble drugs. The physical stability of these two-phase systems, however, is dependent on the carrier material and storage conditions.


Assuntos
Anti-Inflamatórios não Esteroides/química , Química Farmacêutica/métodos , Temperatura Baixa , Indometacina/química , Estabilidade de Medicamentos , Difração de Raios X
17.
J Pharm Sci ; 105(8): 2293-7, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27368121

RESUMO

We introduce a robust, stable, and reproducible method to produce nanoparticles based on expansion of supercritical solutions using carbon dioxide as a solvent. The method, controlled expansion of supercritical solution (CESS), uses controlled mass transfer, flow, pressure reduction, and particle collection in dry ice. CESS offers control over the crystallization process as the pressure in the system is reduced according to a specific profile. Particle formation takes place before the exit nozzle, and condensation is the main mechanism for postnucleation particle growth. A 2-step gradient pressure reduction is used to prevent Mach disk formation and particle growth by coagulation. Controlled particle growth keeps the production process stable. With CESS, we produced piroxicam nanoparticles, 60 mg/h, featuring narrow size distribution (176 ± 53 nm).


Assuntos
Dióxido de Carbono/química , Composição de Medicamentos/métodos , Nanopartículas/química , Preparações Farmacêuticas/química , Cristalização , Composição de Medicamentos/instrumentação , Desenho de Equipamento , Tamanho da Partícula , Piroxicam/química , Pressão , Soluções , Termodinâmica
18.
Int J Pharm ; 508(1-2): 71-82, 2016 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-27163527

RESUMO

In this paper we present a fast model system for monitoring the recrystallization of quench-cooled amorphous xylitol using Raman spectroscopy and wide-angle X-ray scattering. The use of these two methods enables comparison between surface and bulk crystallization. Non-ordered mesoporous silica micro-particles were added to the system in order to alter the rate of crystallization of the amorphous xylitol. Raman measurements showed that adding silica to the system increased the rate of surface crystallization, while X-ray measurements showed that the rate of bulk crystallization decreased. Using this model system it is possible to measure fast changes, which occur in minutes or within a few hours. Raman-spectroscopy and wide-angle X-ray scattering were found to be complementary techniques when assessing surface and bulk crystallization of amorphous xylitol.


Assuntos
Análise Espectral Raman , Difração de Raios X/métodos , Xilitol/química , Cristalização , Dióxido de Silício/química
19.
J Pharm Sci ; 105(3): 1239-47, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26886306

RESUMO

Suberin fatty acids (SFAs) isolated from outer birch bark were investigated as an antimicrobial agent and biomaterial in nanofibrous mats intended for wound treatment. Electrospinning (ES) was used in preparing the composite nonwoven nanomats containing chloramphenicol (CAM; as a primary antimicrobial drug), SFAs, and polyvinylpyrrolidone (as a carrier polymer for ES). The X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy, atomic force microscopy, and texture analysis were used for the physicochemical and mechanical characterization of the nanomats. ES produced nanofibrous mats with uniform structure and with an average fiber diameter ranging from 370 to 425 nm. Microcrystalline SFAs and crystalline CAM were found to undergo a solid-state transformation during ES processing. The ES process caused also the loss of CAM in the final nanofibers. In the texture analysis, the SFAs containing nanofibers exhibited significantly higher maximum detachment force to an isolated pig skin (p < 0.05) than that obtained with the reference nanofibers. CAM exists in an amorphous form in the nanofibers which needs to be taken into account in controlling the physical storage stability. In conclusion, homogeneous composite nanofibrous mats for wound healing can be electrospun from the ternary mixture(s) of CAM, SFAs, and polyvinylpyrrolidone.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Cloranfenicol/química , Ácidos Graxos/química , Lipídeos/química , Nanofibras/química , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Varredura Diferencial de Calorimetria/métodos , Cloranfenicol/farmacologia , Ácidos Graxos/farmacologia , Lipídeos/farmacologia , Microscopia Eletrônica de Varredura/métodos , Polímeros/química , Povidona/química , Pele/efeitos dos fármacos , Suínos , Difração de Raios X/métodos
20.
Drug Dev Ind Pharm ; 42(3): 378-88, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26065533

RESUMO

Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug-polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug-polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used.


Assuntos
Química Farmacêutica/métodos , Portadores de Fármacos/química , Piroxicam/química , Polímeros/química , Água/química , Criopreservação/métodos , Portadores de Fármacos/análise , Piroxicam/análise , Polímeros/análise , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos
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