scholarly journals The Polymorphism of Drugs: New Approaches to the Synthesis of Nanostructured Polymorphs

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 34 ◽  
Author(s):  
Dmitry Chistyakov ◽  
Gleb Sergeev
Keyword(s):  
Physicochemical Properties ◽  
Inert Gases ◽  
Current Interest ◽  
Promising Direction ◽  
Drug Polymorphism ◽  
Polymorphic Forms ◽  
The Stability ◽  
Further Development ◽  
Low Solubility ◽  
Polymorphous Modifications

Among the significant problems of modern pharmacology are the low solubility and bioavailability of drugs. One way to resolve this problem is to obtain new polymorphic forms of drugs with improved physicochemical properties. Various approaches have been developed with this aim, including the preparation of co-crystals, the use of nanoparticles, or the use of compounds in the form of a salt. A promising direction in pharmacology concerns the production of new stable polymorphic structures. In this mini-review, we consider certain aspects of drug polymorphism, methods for the synthesis of polymorphs, and the stability, size, and transformation of crystalline polymorphs. Moreover, we summarize our results from several studies demonstrating the problems associated with the synthesis of new polymorphous modifications based on inert gases and cryotemperatures. The results indicate that the problems specific to drug polymorphisms have only been partly resolved, are of current interest, and require further development.

scholarly journals Evaluation of Polymorphism Influence in the Finasteride

2014 ◽  
Vol 70 (a1) ◽  
pp. C1567-C1567
Author(s):  
Lucélia da Silva ◽  
Cristina Montanari ◽  
Marilene Ângelo ◽  
Edith Cristina Cazedey ◽  
Rudy Bonfilio ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Competitive Inhibitor ◽  
Stability Study ◽  
Dissolution Profile ◽  
X Ray Diffraction ◽  
Intracellular Enzyme ◽  
X Ray ◽  
Solubility Study ◽  
Polymorphic Forms ◽  
The Stability

Finasteride is a specific competitive inhibitor of steroid type-II 5α-reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone (DHT) and is widely used for the treatment of benign prostatic hyperplasia (BPH), prostate cancer , and androgenetic alopecia. Polymorphs are known to give rise to significant differences in the physicochemical properties of the compound as melting point, density, morphology, solubility and colour. Thus, proper monitoring of solid-state forms, both qualitative and quantitative, is crucial in order to ensure high-quality products. The crystal structures of finasteride appear in the Cambridge Crystal Structure Database (CSD) under the codes WOLXOK01 and WOLXOK02 for Form I and WOLXOK03 for Form II. In this context, the aim of this work was study the behavior of the chemical structure and physicochemical properties of polymorphic forms, and to evaluate the possible influence in the dissolution profile and stability of capsules. A stability study was carried out at 500C for 3 months. The Form II of finasteride was obtained by heating Form I to 2350C for 30 minutes. The techniques X-ray diffraction, infrared spectroscopy and thermal analysis were applied to characterize the Forms. The solubility of finasteride polymorphs was determined by equilibrium solubility method. For the dissolution test, water was used as dissolution medium and the basket apparatus at 100 rpm. The samples were analyzed by HPLC at 210 nm. Differences in X-ray diffraction and infrared spectra of the two polymorphs were observed. The DSC curves showed Form I melting peak at 2570C and solid-solid transformation to Form II at about 2300C. In the solubility study was observed higher Form II solubility than Form I in most evaluated pHs. The interaction of the Forms I and II with capsule excipients may have been different since the dissolution profile of the capsules showed higher release to the Form I. In the stability study, the finasteride content was stable for two Forms, however, the dissolution profile of Form II showed greater decline than the Form I. In conclusion, the results show that the dissolution profiles polymorphism may influence the quality of finasteride capsules, being necessary there be a polymorphic quality control for this dosage Form. Acknowledgments: PNPD CAPES and FAPEMIG

The stability of dislocation networks under various oxygen-doping conditions in superconducting Bi2Sr2CaCu2Oy single crystals and their influence on the flux pinning properties

1994 ◽  
Vol 52 ◽  
pp. 802-803
Author(s):  
Y. Feng ◽  
X. Y. Cai ◽  
R. J. Kelley ◽  
D. C. Larbalestier
Keyword(s):  
Single Crystals ◽  
Oxygen Content ◽  
Basal Plane ◽  
Flux Pinning ◽  
Pinning Centers ◽  
Before And After ◽  
Anomalous Peak ◽  
Basal Plane Dislocation ◽  
The Stability ◽  
Further Development

The issue of strong flux pinning is crucial to the further development of high critical current density Bi-Sr-Ca-Cu-O (BSCCO) superconductors in conductor-like applications, yet the pinning mechanisms are still much debated. Anomalous peaks in the M-H (magnetization vs. magnetic field) loops are commonly observed in Bi2Sr2CaCu2Oy (Bi-2212) single crystals. Oxygen vacancies may be effective flux pinning centers in BSCCO, as has been found in YBCO. However, it has also been proposed that basal-plane dislocation networks also act as effective pinning centers. Yang et al. proposed that the characteristic scale of the basal-plane dislocation networksmay strongly depend on oxygen content and the anomalous peak in the M-H loop at ˜20-30K may be due tothe flux pinning of decoupled two-dimensional pancake vortices by the dislocation networks. In light of this, we have performed an insitu observation on the dislocation networks precisely at the same region before and after annealing in air, vacuumand oxygen, in order to verify whether the dislocation networks change with varying oxygen content Inall cases, we have not found any noticeable changes in dislocation structure, regardless of the drastic changes in Tc and the anomalous magnetization. Therefore, it does not appear that the anomalous peak in the M-H loops is controlled by the basal-plane dislocation networks.

scholarly journals Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 359
Author(s):  
Thai Thanh Hoang Thi ◽  
Estelle J. A. Suys ◽  
Jung Seok Lee ◽  
Dai Hai Nguyen ◽  
Ki Dong Park ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Clinical Trials ◽  
Physicochemical Properties ◽  
Solid Lipid Nanoparticles ◽  
Drug Delivery Systems ◽  
Lipid Nanoparticles ◽  
Therapeutic Vaccines ◽  
Cancer Nanomedicine ◽  
Fundamental Research ◽  
Further Development

COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil® and Onpattro®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.

scholarly journals A Novel In Vitro Approach for Simultaneous Evaluation of CYP3A4 Inhibition and Kinetic Aqueous Solubility

2014 ◽  
Vol 20 (2) ◽  
pp. 254-264 ◽  
Author(s):  
José Pérez ◽  
Caridad Díaz ◽  
Francisco Asensio ◽  
Alexandra Palafox ◽  
Olga Genilloud ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Physicochemical Properties ◽  
Safety Concern ◽  
Aqueous Solubility ◽  
Cyp3a4 Inhibition ◽  
Use Of Resources ◽  
Simultaneous Evaluation ◽  
New Chemical Entities ◽  
Further Development

In the early stages of the drug discovery process, evaluation of the drug metabolism and physicochemical properties of new chemical entities is crucial to prioritize those candidates displaying a better profile for further development. In terms of metabolism, drug–drug interactions mediated through CYP450 inhibition are a significant safety concern, and therefore the effect of new candidate drugs on CYP450 activity should be screened early. In the initial stages of drug discovery, when physicochemical properties such as aqueous solubility have not been optimized yet, there might be a large number of candidate compounds showing artificially low CYP450 inhibition, and consequently potential drug–drug interaction toxicity might be overlooked. In this work, we present a novel in vitro approach for simultaneous evaluation of CYP3A4 inhibition potential and kinetic aqueous solubility (NIVA-CYPI-KS). This new methodology is based on fluorogenic CYP450 activities and turbidimetric measurements for compound solubility, and it provides a significant improvement in the use of resources and a better understanding of CYP450 inhibition data.

Stability of the Professional Development Assessment

1997 ◽  
Vol 84 (3_suppl) ◽  
pp. 1373-1374
Author(s):  
Jack Kasar
Keyword(s):  
Professional Development ◽  
Occupational Therapy ◽  
Professional Behaviors ◽  
The Stability ◽  
Development Assessment ◽  
Further Development

The Professional Development Assessment was constructed and pilot-tested with 76 students in three occupational therapy programs. A comparison of pretest and posttest scores yielded a significant correlation of .48, supporting the stability of responding over 1 to 2 years and suggesting usefulness of further development for evaluation of professional behaviors in students.

scholarly journals Natural Gums to Improve the Physicochemical Stability of Cake Creams

Foods ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2261
Author(s):  
Oscar López-Balladares ◽  
Patricio J. Espinoza-Montero ◽  
Ramiro Acosta-Sandoval
Keyword(s):  
Physicochemical Properties ◽  
Elastic Deformation ◽  
Bubble Size ◽  
Physicochemical Changes ◽  
Physicochemical Stability ◽  
Confectionery Products ◽  
Initial Appearance ◽  
Thixotropic Behavior ◽  
The Aesthetic ◽  
The Stability

The physicochemical properties of pastry and confectionery products greatly influence the aesthetic design of a cake topping, since they can be susceptible to physicochemical changes in a very short time, so maintaining a good appearance and texture of the topping becomes a challenge. Generally, cake creams deteriorate over time. The evaluation of the physicochemical properties of natural gums (arabic gum, tara gum, carrageenan, and pectin) is proposed in this work as a way to improve the physicochemical stability of butter-based cake creams (coverage creams) to maintain the initial appearance of the cream and to lengthen the separation time of their phases. For this purpose, some parameters related to the physicochemical stability of the cream, such as viscosity, density, bubble size, syneresis, volume and rheological behavior were measured. The result of the ANOVA and Tukey’s tests displayed significant differences for the measured parameters, which shows that natural gums substantially improve the stability of butter cream. The best natural gum found was the tara gum (TG) which improved viscosity 5.6 times with respect to that of the cream without gums (η¯ without gums = 15.49 Pa·s, η¯ with TG = 87.09 Pa·s), while the bubble size remained small, 1.6 times smaller compared to that of the cream without gum (BS¯) without gums = 57 μm, (BS¯) with TG = 35 μm), and the volume loss decreased two times when compared to that of the cream without gums ((ΔV¯) without gums = 1.57 cm3, (ΔV¯) with TG = 0.80 cm3). The cream with TG showed better rheology compared to that of the cream without gums (the cream without gums exhibited a plastic and thixotropic behavior, with permanent elastic deformation, while cream with TG exhibited thixotropic behavior without permanent elastic deformation). Finally, it was found that the cream with TG acquired a higher thixotropic index (TI) compared to that of the cream without gums (TI max. without gums = 17.40 y 71.78 q.u., TI max. with TG = 74.67 and 1559.90 q.u., at 4 °C and 25 °C, respectively) which demonstrates the effective contribution of cream with TG in 66.67% of the measured parameters.

scholarly journals Influence of Powder-to-Gel Ratio on Physicochemical Properties of a Calcium Silicate Sealer

2020 ◽  
pp. 337-345
Author(s):  
Fernanda F. E. Torres ◽  
Patricia Perinoto ◽  
Roberta Bosso-Martelo ◽  
Gisselle M. Chávez-Andrade ◽  
Juliane M. Guerreiro-Tanomaru ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Calcium Silicate ◽  
Setting Time ◽  
Repair Material ◽  
Alkaline Ph ◽  
Root Canal Sealer ◽  
Work Time ◽  
Lower Solubility ◽  
Low Solubility ◽  
One Way Anova

Differences in liquid-to-powder ratio can affect the properties of calcium silicate-based materials. This study assessed the influence of powder-to-gel ratio on physicochemical properties of NeoMTA Plus. Setting time (minutes), flow (mm and mm²), pH (at different periods), radiopacity (mm Al) and solubility (% mass loss) were evaluated using the consistencies for root repair material (NMTAP-RP; 3 scoops of powder to 2 drops of gel) and root canal sealer (NMTAP-SE; 3 scoops of powder to 3 drops of gel), in comparison to Biodentine cement (BIO) and TotalFill BC sealer (TFBC). Statistical analysis was performed using one-way ANOVA and Tukey tests (α=0.05). BIO had the shortest setting time, followed by NMTAP-RP and NMTAP-SE. TFBC showed the highest setting time and radiopacity. BIO, NMTAP-RP, and NMTAP-SE had similar radiopacity. All materials promoted an alkaline pH. NMTAP-RP/SE presented lower solubility than BIO and TFBC. Regarding the flow, TFBC had the highest values, followed by NMTAP-SE, and NMTAP-RP. BIO had the lowest flow. In conclusion, NMTAP in both powder-to-gel ratios showed high pH and low solubility. The increase in the powder ratio decreased the setting time and flow. These findings are important regarding the proper consistency and work time to clinical application.

scholarly journals Physicochemical Properties and Stability of Microencapsulated Betacyanin Pigments from Red Dragon Fruit Peels and Flesh

2020 ◽  
pp. 141-148
Author(s):  
Rosalinda C Torres ◽  
Rowelain Mae G Yumang ◽  
Chelsea Kate F Jose ◽  
Danielle Camille P Canillo
Keyword(s):  
Moisture Content ◽  
Physicochemical Properties ◽  
Morphological Characterization ◽  
Stability Study ◽  
Natural Colorant ◽  
Hygroscopic Moisture ◽  
Dragon Fruit ◽  
The Stability ◽  
Spray Dried ◽  
Hylocereus Polyrhizus

Dragon fruit (Hylocereus polyrhizus) is known for its purple-coloured peels and pulp, which can be attributed to the presence of betalains. In this study, the potential of red dragon fruit as a source of natural colorant was investigated. Betacyanins were extracted from red dragon fruit peels and flesh in 1:3 ratio with water. Microencapsulation by spray-drying was done by adding 5% and 10% (w/v) maltodextrin (DE 11.8) to peels and flesh extracts, respectively. The spray-dried colorant powders all obtained <10% moisture content, 5.261-6.409 g/100g hygroscopic moisture content, and 5.317-7.349(mg/100L) betacyanin content. Morphological characterization revealed spherical, agglomerated particles with visible cracks on the surface. The stability study conducted showed that pigment retention was lowest at 70°C and highest at 4°C. Keywords: Hylocereus polyrhizus; Red dragon fruit; Betacyanin; Microencapsulation; Physicochemical properties

Importance of oscillations in alveolar gas concentrations in the analysis of rebreathing data

1986 ◽  
Vol 61 (3) ◽  
pp. 1104-1113 ◽  
Author(s):  
K. H. Weisiger ◽  
G. D. Swanson
Keyword(s):  
Time Course ◽  
Continuous Process ◽  
Inert Gases ◽  
Accurate Estimation ◽  
Gas Solubility ◽  
Estimation Errors ◽  
Gas Uptake ◽  
Cyclic Model ◽  
Low Solubility ◽  
Cyclic Data

Cyclic rebreathing of a soluble inert gas can be used to estimate lung tissue volume (Vt) and pulmonary blood flow (Qc). A recently proposed method for analyzing such cyclic data (Respir. Physiol. 48: 255–279, 1982) mathematically assumes that ventilation is a continuous process. However, neglecting the cyclic nature of ventilation may prevent the accurate estimation of Vt and Qc. We evaluated this possibility by simulating the uptake of soluble inert gases during rebreathing using a cyclic model of gas exchange. Under cyclic uptake conditions alveolar gases follow an oscillating time course, because gas concentrations tend to increase during inspiration and to decrease during expiration. We found that neglecting these alveolar gas oscillations leads to the underestimation of soluble gas uptake by blood, particularly during the early rebreathing breaths. When continuous ventilation is assumed Vt and Qc are overestimated unless rapid rebreathing rates, large tidal volumes, and gases of moderately low solubility are used. Under these conditions the amplitude of the cyclic oscillations is minimized, the alveolar time course more closely resembles that expected from continuous ventilation, and the resulting errors are minimized. Alternatively, when the effect of oscillating alveolar gas concentrations on mass transfer are considered, these estimation errors can be eliminated without restricting rebreathing rate or gas solubility. We conclude that failure to consider the effect of cyclic rebreathing on the time course of alveolar gas concentrations may result in significant errors when evaluating rebreathing data for Vt and Qc.

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