scholarly journals A Multivariate Approach for the Determination of the Optimal Mixing Ratio of the Non-Strong Interacting Co-Amorphous System Carvedilol-Tryptophan

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 801
Author(s):  
Rong Di ◽  
Jingwen Liu ◽  
Holger Grohganz ◽  
Thomas Rades
Keyword(s):  
Physical Stability ◽  
Principal Component ◽  
Water Soluble ◽  
Mixing Ratio ◽  
Scanning Calorimetry ◽  
Amorphous Systems ◽  
Amorphous System ◽  
Novel Approach ◽  
Water Soluble Drugs ◽  
Optimal Mixing

Converting crystalline compounds into co-amorphous systems is an effective way to improve the solubility of poorly water-soluble drugs. It is, however, of critical importance for the physical stability of co-amorphous systems to find the optimal mixing ratio of the drug with the co-former. In this study, a novel approach for this challenge is presented, exemplified with the co-amorphous system carvedilol–tryptophan (CAR–TRP). Following X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) of the ball-milled samples to confirm their amorphous form, Fourier-transform infrared spectroscopy (FTIR) and principal component analysis (PCA) were applied to investigate intermolecular interactions. A clear deviation from a purely additive spectrum of CAR and TRP was visualized in the PCA score plot, with a maximum at around 30% drug (mol/mol). This deviation was attributed to hydrogen bonds of CAR with TRP ether groups. The sample containing 30% drug (mol/mol) was also the most stable sample during a stability test. Using the combination of FTIR with PCA is an effective approach to investigate the optimal mixing ratio of non-strong interacting co-amorphous systems.

scholarly journals Applicability of an Experimental Grade of Hydroxypropyl Methylcellulose Acetate Succinate as a Carrier for Formation of Solid Dispersion with Indomethacin

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 353
Author(s):  
Hiroshi Ueda ◽  
Yuya Hirakawa ◽  
Hironori Tanaka ◽  
Tetsuya Miyano ◽  
Katsuji Sugita
Keyword(s):  
Solid Dispersion ◽  
Hydroxypropyl Methylcellulose ◽  
Principal Component ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Amorphous Solid Dispersion ◽  
Scanning Calorimetry ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Amorphous Drug

The transformation of a crystalline drug into an amorphous form is a promising way to enhance the oral bioavailability of poorly water-soluble drugs. Blending of a carrier, such as a hydrophilic polymer, with an amorphous drug is a widely used method to produce a solid dispersion and inhibit crystallization. This study investigates an experimental grade of hydroxypropyl methylcellulose acetate succinate, HPMCAS-MX (MX), as a solid dispersion carrier. Enhancement of thermal stability and reduction of the glass transition temperature (Tg) of MX compared with those of the conventional grade were evaluated through thermogravimetric analysis and differential scanning calorimetry (DSC). The formation of a homogeneous amorphous solid dispersion between MX and indomethacin was confirmed by X-ray powder diffraction analysis, DSC, and Raman mapping. It was observed that 10–30% MX did not act as an anti-plasticizer, but the utilization of >40% MX caused an increase in Tg and reduction of molecular mobility. This could be explained by a change in intermolecular interactions, inferred from infrared spectroscopy combined with principal component analysis. HPMCAS-MX exhibited similar performance to that of conventional-grade, HPMCAS-MG. Although HPMCAS-MX has thermal properties different from those of conventional-grade HPMCAS-MG, it retains its ability as a solid dispersion carrier.

scholarly journals Preparation of Co-Amorphous Systems by Freeze-Drying

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 941
Author(s):  
Melvin Wostry ◽  
Hanna Plappert ◽  
Holger Grohganz
Keyword(s):  
Amino Acid ◽  
Freeze Drying ◽  
Sodium Dodecyl ◽  
Solid Content ◽  
Water Soluble ◽  
Tween 20 ◽  
Scanning Calorimetry ◽  
Total Solid Content ◽  
Amorphous Systems ◽  
Freeze Dried

Freeze-drying was evaluated as a production technique for co-amorphous systems of a poorly water-soluble drug. Naproxen was freeze-dried together with arginine and lysine as co-former. To increase the solubility of naproxen in the starting solution, the applicability of five surfactants was investigated, namely sodium dodecyl sulfate, pluronic F-127, polyoxyethylene (40) stearate, tween 20 and TPGS 1000. The influence of the surfactant type, surfactant concentration and total solid content to be freeze-dried on the solid state of the sample was investigated. X-ray powder diffraction and differential scanning calorimetry showed that the majority of systems formed co-amorphous one-phase systems. However, at higher surfactant concentrations, and depending on the surfactant type, surfactant reflections were observed in the XRPD analysis upon production. Crystallization of both naproxen and amino acid occurred from some combinations under storage. In conclusion, freeze-drying was shown to be a feasible technique for the production of a selection of co-amorphous drug–amino acid formulations.

scholarly journals Synthesis of Tungsten-Doped Vanadium Dioxide Using a Modified Polyol Method Involving 1-Dodecanol

Materials ◽  
2020 ◽  
Vol 13 (23) ◽  
pp. 5384
Author(s):  
Yonghyun Lee ◽  
Sang Won Jung ◽  
Sang Hwi Park ◽  
Jung Whan Yoo ◽  
Juhyun Park
Keyword(s):  
Linear Growth ◽  
Mixing Ratio ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Metal Insulator ◽  
X Ray ◽  
Mixing Ratios ◽  
The Difference ◽  
Modified Polyol Method ◽  
Optimal Mixing

The doping of tungsten into VO2 (M) via a polyol process that is based on oligomerization of ammonium metavanadate and ethylene glycol (EG) to synthesize a vanadyl ethylene glycolate (VEG) followed by postcalcination was carried out by simply adding 1-dodecanol and the tungsten source tungstenoxytetrachloride (WOCl4). Tungsten-doped VEGs (W-VEGs) and their calcinated compounds (WxVO2) were prepared with varying mixing ratios of EG to 1-dodecanol and WOCl4 concentrations. Characterizations of W-VEGs by powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and infrared and transmittance spectroscopy showed that tungsten elements were successfully doped into WxVO2, thereby decreasing the metal-insulator transition temperature from 68 down to 51 °C. Our results suggested that WOCl4 variously combined with 1-dodecanol might interrupt the linear growth of W-VEGs, but that such an interruption might be alleviated at the optimal 1:1 mixing ratio of EG to 1-dodecanol, resulting in the successful W doping. The difference in the solar modulations of a W0.0207VO2 dispersion measured at 20 and 70 °C was increased to 21.8% while that of a pure VO2 dispersion was 2.5%. It was suggested that WOCl4 coupled with both EG and 1-dodecanol at an optimal mixing ratio could improve the formation of W-VEG and WxVO2 and that the bulky dodecyl chains might act as defects to decrease crystallinity.

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 Solid dispersion a novel approach for enhancement of solubility and dissolution rate: a review

2019 ◽  
Vol 7 (03) ◽  
pp. 05-11
Author(s):  
Diksha Thakur ◽  
Rambabu Sharma
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Hepatic Metabolism ◽  
Oral Route ◽  
Review Article ◽  
Water Soluble ◽  
Solid Dosage ◽  
Novel Approach ◽  
Water Soluble Drugs

The oral route is the most preferred route for the administration of various drugs because it is the most convenient and safest route for drug delivery. The researcher develops a recently fast dissolving tablet (FDT). This improved patient compliance and convenience. FDTs are defining as the solid dosage form, which disintegrates in saliva without the need for water. Solid dispersions attract considerable interest by increasing the dissolution rate and also enhance the bioavailability of poor water-soluble drugs. Pre-gastric absorption avoids first-pass hepatic metabolism, which increases the bioavailability of the drug. One part of the review article focus on solid dispersion, there advantages, disadvantages, and method of preparation. Later part of the review article focus on the evaluation of fast dissolving tablet.

scholarly journals Improving the Solubility of Aripiprazole by Multicomponent Crystallization

Crystals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 343
Author(s):  
Qi Zhou ◽  
Zhongchuan Tan ◽  
Desen Yang ◽  
Jiyuan Tu ◽  
Yezi Wang ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Weak Interactions ◽  
Theoretical Calculations ◽  
Water Soluble ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Intrinsic Dissolution ◽  
Intrinsic Dissolution Rate ◽  
X Ray ◽  
Water Soluble Drugs

Aripiprazole (ARI) is a third-generation antipsychotic with few side effects but a poor solubility. Salt formation, as one common form of multicomponent crystals, is an effective strategy to improve pharmacokinetic profiles. In this work, a new ARI salt with adipic acid (ADI) and its acetone hemisolvate were obtained successfully, along with a known ARI salt with salicylic acid (SAL). Their comprehensive characterizations were conducted using X-ray diffraction and differential scanning calorimetry. The crystal structures of the ARI-ADI salt acetone hemisolvate and ARI-SAL salt were elucidated by single-crystal X-ray diffraction for the first time, demonstrating the proton transfer from a carboxyl group of acid to ARI piperazine. Theoretical calculations were also performed on weak interactions. Moreover, comparative studies on pharmaceutical properties, including powder hygroscopicity, stability, solubility, and the intrinsic dissolution rate, were carried out. The results indicated that the solubility and intrinsic dissolution rate of the ARI-ADI salt and its acetone hemisolvate significantly improved, clearly outperforming that of the ARI-SAL salt and the untreated ARI. The study presented one potential alternative salt of aripiprazole and provided a potential strategy to increase the solubility of poorly water-soluble drugs.

An inert 3D emulsification device for individual precipitation and concentration of amorphous drug nanoparticles

Lab on a Chip ◽  
2018 ◽  
Vol 18 (4) ◽  
pp. 627-638 ◽  
Author(s):  
T. Lorenz ◽  
S. Bojko ◽  
H. Bunjes ◽  
A. Dietzel
Keyword(s):  
Specific Surface ◽  
Water Soluble ◽  
Poorly Water Soluble Drugs ◽  
Drug Nanoparticles ◽  
Novel Approach ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Amorphous Drug

Nanosizing increases the specific surface of drug particles, leading to faster dissolution inside the organism and improving the bioavailability of poorly water-soluble drugs. A novel approach for the preparation of drug nanoparticles in water using chemically inert microfluidic emulsification devices is presented.

DEVELOPMENT OF SOLID DISPERSION TABLET OF CARVEDILOL TO IMPROVE SOLUBILITY

INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (01) ◽  
pp. 54-59
Author(s):  
S. S Shelake ◽  
◽  
R. G Gaikwad ◽  
S Patil ◽  
F. I. Mevekari ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Aqueous Media ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Scanning Calorimetry ◽  
Water Soluble Drugs ◽  
Ft Ir

Crystalline state compounds are typically dissolution rate limited and dissolution rate is directly proportional to the solubility for BCS class II or class IV compounds. Solid dispersions are one of the most promising strategies to improve the oral bioavailability poorly water soluble drugs. The purpose of this study was to increase solubility of carvedilol by solid dispersion (SDs) technique with Poloxamer (PXM) 407 in aqueous media. The carvedilol- PXM 407 solid dispersion was prepared by solvent evaporation, kneading and melting method. It was characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), Fourier transformation infra-red spectroscopy (FT-IR), scanning electron microscopy (SEM) and in vitro dissolution studies. The prepared solid dispersion were found to have higher dissolution rates as compared to intact carvedilol. During formulation of solid dispersion crystalline to amorphous transition has been observed.

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