scholarly journals Microspherical Particles of Solid Dispersion of Polyvinylpyrrolidone K29-32 for Inhalation Administration

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
L. S. Usmanova ◽  
M. A. Ziganshin ◽  
I. T. Rakipov ◽  
N. M. Lyadov ◽  
A. E. Klimovitskii ◽  
...  
Keyword(s):  
Spray Drying ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Optimal Size ◽  
Drying Process ◽  
Promising Alternative ◽  
Poorly Soluble ◽  
Model Drug ◽  
Pharmaceutical Properties ◽  
Inhalation Administration

Inhalation administration is a promising alternative to the invasive drug delivery methods. The particle size required for ideal drug aerosol preparation is between 1 and 3 μm. The application of microspherical particles of solid dispersions enhances bioavailability of poorly soluble drugs due to the solubilization. In the present work, the spray drying process of the production of microspherical particles of solid dispersions of polyvinylpyrrolidone K29-32 with model hydrophobic drug, phenacetin, was optimized using the results of DSC, PXRD, and viscometry. The diameter of the obtained particles is within 1–3 μm range. The Gibbs energy of dissolution in water was shown to be negative for the mixture with polymer/phenacetin mass ratio 5 : 1. We have demonstrated that the optimal size distribution for the inhalation administration is obtained for microspherical particles produced using spray caps with 7.0 μm hole size. The dissolution rates of phenacetin from the produced microspherical particles were faster than that of drug powder. As evidenced by powder X-ray diffraction data, phenacetin stayed in amorphous state for 4 months in microspherical particles of solid dispersions. According to the obtained results, strategic application of the spray drying process could be beneficial for the improvement of the pharmaceutical properties of model drug, phenacetin.

scholarly journals Design and Characterization of Phosphatidylcholine-Based Solid Dispersions of Aprepitant for Enhanced Solubility and Dissolution

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 407
Author(s):  
Sooho Yeo ◽  
Jieun An ◽  
Changhee Park ◽  
Dohyun Kim ◽  
Jaehwi Lee
Keyword(s):  
Solid Dispersion ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
Promising Alternative ◽  
Dispersion System ◽  
Enhanced Solubility ◽  
Water Soluble Drugs

This study aimed to improve the solubility and dissolution of aprepitant, a drug with poor aqueous solubility, using a phosphatidylcholine (PC)-based solid dispersion system. When fabricating the PC-based solid dispersion, we employed mesoporous microparticles, as an adsorbent, and disintegrants to improve the sticky nature of PC and dissolution of aprepitant, respectively. The solid dispersions were prepared by a solvent evaporation technique and characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry, and X-ray powder diffraction. The FTIR results showed that aprepitant interacted with the PC carrier by both hydrogen bonds and van der Waals forces that can also be observed in the interaction between aprepitant and polymer carriers. The solid dispersions fabricated with only PC were not sufficient to convert the crystallinity of aprepitant to an amorphous state, whereas the formulations that included adsorbent and disintegrant successfully changed that of aprepitant to an amorphous state. Both the solubility and dissolution of aprepitant were considerably enhanced in the PC-based solid dispersions containing adsorbent and disintegrant compared with those of pure aprepitant and polymer-based solid dispersions. Therefore, these results suggest that our PC-based solid dispersion system is a promising alternative to conventional formulations for poorly water-soluble drugs, such as aprepitant.

scholarly journals Fluoroquinolone Amorphous Polymeric Salts and Dispersions for Veterinary Uses

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 268 ◽  
Author(s):  
Hanah Mesallati ◽  
Anita Umerska ◽  
Lidia Tajber
Keyword(s):  
Solid Dispersions ◽  
Hydroxypropyl Methylcellulose ◽  
Amorphous Solid ◽  
Ionic Bond ◽  
Amorphous Solid Dispersions ◽  
X Ray ◽  
Poorly Soluble ◽  
Pure Drug ◽  
Poorly Soluble Drug ◽  
Pharmaceutical Properties

Enrofloxacin (ENRO) is a poorly soluble drug used in veterinary medicine. It differs from the more widely used fluoroquinolone ciprofloxacin (CIP) by the presence of an ethyl substituent on its piperazine amino group. While a number of recent studies have examined amorphous composite formulations of CIP, little research has been conducted with ENRO in this area. Therefore, the main purpose of this work was to produce amorphous solid dispersions (ASDs) of ENRO. The solid-state properties of these samples were investigated and compared to those of the equivalent CIP ASDs, and their water uptake behavior, solubility, dissolution, and antibacterial activity were assessed. Like CIP, X-ray amorphous solid dispersions were obtained when ENRO was ball milled with acidic polymers, whereas the use of neutral polymers resulted in semi-crystalline products. Proton transfer from the carboxylic acids of the polymers to the tertiary amine of ENRO’s piperazine group appears to occur in the ASDs, resulting in an ionic bond between the two components. Therefore, these ASDs can be referred to as amorphous polymeric salts (APSs). The glass transition temperatures of the APSs were significantly higher than that of ENRO, and they were also resistant to crystallization when exposed to high humidity levels. Greater concentrations were achieved with the APSs than the pure drug during solubility and dissolution studies, and this enhancement was sustained for the duration of the experiments. In addition, the antimicrobial activity of ENRO was not affected by APS formation, while the minimum inhibitory concentrations and minimum bactericidal concentrations obtained with the APS containing hydroxypropyl methylcellulose acetate succinate grade MG (HPMCAS-MG) were significantly lower than those of the pure drug. Therefore, APS formation is one method of improving the pharmaceutical properties of this drug.

scholarly journals Enhanced Dissolution Efficiency of Tamoxifen Combined with Methacrylate Copolymers in Amorphous Solid Dispersions

Crystals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1046
Author(s):  
Dayanne T. C. da Silva ◽  
Daniela Nadvorny ◽  
Lucas J. de A. Danda ◽  
Amanda C. Q. de M. Vieira ◽  
Patricia Severino ◽  
...  
Keyword(s):  
Drug Loading ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Physical Mixture ◽  
Polymer Mixture ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
Acrylate Copolymer ◽  
Poorly Soluble

Amorphous solid dispersions (SDs) containing poorly soluble tamoxifen dispersed in a meth(acrylate) copolymer combination were proposed as a controlled release system. The objective of this work was to investigate the characteristics and performance of the tamoxifen–polymer mixture and evaluate the changes in functionality through a supersaturating dissolution study condition while comparing it to a physical mixture at a fixed drug-loading proportion. Two polymers, Eudragit® L 100 and Eudragit® RL 100, were used to prepare SDs with a 1:1 polymer ratio, containing 10%, 20%, or 30% (wt/wt%) of tamoxifen, by the solvent evaporation method. A physical mixture containing 30% of tamoxifen was also prepared for comparison. SDs were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Dissolution tests were conducted under non-sink conditions to verify the occurrence of drug recrystallization upon its release. Solid-state characterizations confirmed that the drug was in the amorphous state within the polymeric matrix. Tamoxifen release in an acidic medium was mainly affected by the increase in drug concentration caused by the possible loss of interactions that characterize the main polymer functionalities. At pH 7.4, supersaturation was slowly achieved while also contributing to the increase in the kinetic solubility of the drug. The physical mixture demonstrated the best overall performance, suggesting that the polymeric interactions may have negatively affected the drug release. The combination of polymers in the composing SD proved to be a promising strategy to tailor the delivery of poorly soluble drugs. Our study highlights important information on the behavior of tamoxifen as a poorly soluble drug in supersaturating dissolution conditions while released from SD systems.

scholarly journals The Self-Assembly Phenomenon of Poloxamers and Its Effect on the Dissolution of a Poorly Soluble Drug from Solid Dispersions Obtained by Solvent Methods

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 130 ◽  
Author(s):  
Joanna Szafraniec ◽  
Agata Antosik ◽  
Justyna Knapik-Kowalczuk ◽  
Krzysztof Chmiel ◽  
Mateusz Kurek ◽  
...  
Keyword(s):  
Spray Drying ◽  
Self Assembly ◽  
Binary Systems ◽  
Solid Dispersions ◽  
Water Soluble ◽  
The Self ◽  
Drug Dissolution ◽  
Reduced Pressure ◽  
Wide Range ◽  
Poorly Soluble

The self-assembly phenomenon of amphiphiles has attracted particular attention in recent years due to its wide range of applications. The formation of nanoassemblies able to solubilize sparingly water-soluble drugs was found to be a strategy to solve the problem of poor solubility of active pharmaceutical ingredients. Binary and ternary solid dispersions containing Biopharmaceutics Classification System (BCS) class II drug bicalutamide and either Poloxamer®188 or Poloxamer®407 as the surface active agents were obtained by either spray drying or solvent evaporation under reduced pressure. Both processes led to morphological changes and a reduction of particle size, as confirmed by scanning electron microscopy and laser diffraction measurements. The increase in powder wettability was confirmed by means of contact angle measurements. The effect of an alteration of the crystal structure was followed by powder X-ray diffractometry while thermal properties were determined using differential scanning calorimetry. Interestingly, bicalutamide exhibited a polymorph transition after spray drying with the poloxamer and polyvinylpyrrolidone (PVP), while the poloxamer underwent partial amorphization. Moreover, due to the surface activity of the carrier, the solid dispersions formed nanoaggregates in water, as confirmed using dynamic light scattering measurements. The aggregates measuring 200–300 nm in diameter were able to solubilize bicalutamide inside the hydrophobic inner parts. The self-assembly of binary systems was found to improve the amount of dissolved bicalutamide by 4- to 8-fold in comparison to untreated drug. The improvement in drug dissolution was correlated with the solubilization of poorly soluble molecules by macromolecules, as assessed using emission spectroscopy.

scholarly journals Solvent-Assisted Secondary Drying of Spray-Dried Polymers

2020 ◽  
Vol 37 (8) ◽  
Author(s):  
Kimberly B. Shepard ◽  
April M. Dower ◽  
Alyssa M. Ekdahl ◽  
Michael M. Morgen ◽  
John M. Baumann ◽  
...  
Keyword(s):  
Spray Drying ◽  
Solid Dispersions ◽  
Model Systems ◽  
Process Time ◽  
Drying Methods ◽  
Drying Process ◽  
Free Volume Theory ◽  
Residual Solvent ◽  
Secondary Drying ◽  
Spray Dried

Abstract Purpose The purpose of this work is to introduce solvent-assisted secondary drying, a method used to accelerate the residual solvent removal from spray dried materials. Spray-drying is used to manufacture amorphous solid dispersions, which enhance the bioavailability of active pharmaceutical ingredients (APIs) with low aqueous solubility. In the spray-drying process, API and excipients are co-dissolved in a volatile organic solvent, atomized into droplets through a nozzle, and introduced to a drying chamber containing heated nitrogen gas. The product dries rapidly to form a powder, but small amounts of residual solvent (typically, 1 to 10 wt%) remain in the product and must be removed in a secondary-drying process. For some spray-dried materials, secondary drying by traditional techniques can take days and requires balancing stability risks with process time. Methods Spray-dried polymers were secondary dried, comparing the results for three state-of-the-art methods that employed a jacketed, agitated-vessel dryer: (1) vacuum-only drying, (2) water-assisted drying, or (3) methanol-assisted drying. Samples of material were pulled at various time points and analyzed by gas chromatography (GC) and Karl Fischer (KF) titration to track the drying process. Results Model systems were chosen for which secondary drying is slow. For all cases studied, methanol-assisted drying outperformed the vacuum-only and water-assisted drying methods. Conclusions The observation that methanol-assisted drying is more effective than the other drying techniques is consistent with the free-volume theory of solvent diffusion in polymers.

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