scholarly journals Determination of Stable Co-Amorphous Drug–Drug Ratios from the Eutectic Behavior of Crystalline Physical Mixtures

Pharmaceutics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 628 ◽  
Author(s):  
Eric Ofosu Kissi ◽  
Keyoomars Khorami ◽  
Thomas Rades
Keyword(s):  
Phase Diagrams ◽  
Physical Stability ◽  
Eutectic Point ◽  
Stability Study ◽  
Scanning Calorimetry ◽  
Amorphous Systems ◽  
Eutectic Mixtures ◽  
Amorphous Drugs ◽  
Dry Conditions ◽  
Amorphous Drug

Co-amorphous drug–drug systems have been developed with the overall aim of improving the physical stability of two or more amorphous drugs. Co-amorphous systems often show good physical stability, and higher solubility and dissolution rates compared to their crystalline counterparts. The aim of this study is to determine if eutectic mixtures of two drugs can form stable co-amorphous systems. Three drug–drug mixtures, indomethacin–naproxen (IND−NAP), nifedipine–paracetamol (NIF−PAR), and paracetamol–celecoxib (PAR−CCX), were investigated for their eutectic and co-amorphization behavior as well as their physical stability in the co-amorphous form. The phase diagrams of the crystalline mixtures and the thermal behavior of the co-amorphous systems were analyzed by differential scanning calorimetry. The solid-state form and physical stability of the co-amorphous systems were analyzed using X-ray powder diffractometry during storage at room temperature at dry conditions. Initial eutectic screening using nifedipine (NIF), paracetamol (PAR), and celecoxib (CCX) indicated that IND−NAP, NIF−PAR, and PAR−CCX can form eutectic mixtures. Phase diagrams were then constructed using theoretical and experimental values. These systems, at different drug-to-drug ratios, were melted and cooled to form binary mixtures. Most mixtures were found to be co-amorphous systems, as they were amorphous and exhibited a single glass transition temperature. The stability study of the co-amorphous systems indicated differences in their physical stability. Comparing the phase diagrams with the physical stability of the co-amorphous mixtures, it was evident that the respective drug–drug ratio that forms the eutectic point also forms the most stable co-amorphous system. The eutectic behavior of drug–drug systems can thus be used to predict drug ratios that form the most stable co-amorphous systems.

scholarly journals Development of spray-dried co-precipitate of amorphous celecoxib containing storage and compression stabilizers

2007 ◽  
Vol 57 (3) ◽  
pp. 287-300 ◽  
Author(s):  
Ravindra Dhumal ◽  
Shamkant Shimpi ◽  
Anant Paradkar
Keyword(s):  
Hydrogen Bonding ◽  
Solid Dispersion ◽  
Dissolution Profile ◽  
Scanning Calorimetry ◽  
Unit Operations ◽  
Bonding Interaction ◽  
Amorphous Drugs ◽  
The Stability ◽  
Amorphous Drug ◽  
Spray Dried

Development of spray-dried co-precipitate of amorphous celecoxib containing storage and compression stabilizersThe purpose of this study was to obtain an amorphous system with minimum unit operations that will prevent recrystallization of amorphous drugs since preparation, during processing (compression) and further storage. Amorphous celecoxib, solid dispersion (SD) of celecoxib with polyvinyl pyrrollidone (PVP) and co-precipitate with PVP and carrageenan (CAR) in different ratios were prepared by the spray drying technique and compressed into tablets. Saturation solubility and dissolution studies were performed to differentiate performance after processing. Differential scanning calorimetry and X-ray powder difraction revealed the amorphous form of celecoxib, whereas infrared spectroscopy revealed hydrogen bonding between celecoxib and PVP. The dissolution profile of the solid dispersion and co-precipitate improved compared to celecoxib and amorphous celecoxib. Amorphous celecoxib was not stable on storage whereas the solid dispersion and co-precipitate powders were stable for 3 months. Tablets of the solid dispersion of celecoxib with PVP and physical mixture with PVP and carrageenan showed better resistance to recrystallization than amorphous celecoxib during compression but recrystallized on storage. However, tablets of co-precipitate with PVP and carageenan showed no evidence of crystallinity during stability studies with comparable dissolution profiles. This extraordinary stability of spray-dried co-precipitate tablets may be attributed to the cushioning action provided by the viscoelastic polymer CAR and hydrogen bonding interaction between celecoxib and PVP. The present study demonstrates the synergistic effect of combining two types of stabilizers, PVP and CAR, on the stability of amorphous drug during compression and storage as compared to their effect when used alone.

Development of Oral Microemulsions of Morus alba Extract for Osteoarthritis

2014 ◽  
Vol 1060 ◽  
pp. 41-44
Author(s):  
Thapani Noi-Ang ◽  
Anusorn Charoensin ◽  
Aksiporn Warangkanagool ◽  
Athid Kulkong ◽  
Nattaporn Soonthornsit ◽  
...  
Keyword(s):  
Phase Diagrams ◽  
High Performance ◽  
Room Temperature ◽  
Ternary Phase ◽  
Physical Stability ◽  
Visual Observation ◽  
Stability Study ◽  
Ternary Phase Diagrams ◽  
The Stability ◽  
Precipitation Phase

This study aimed to develop oral microemulsions (MEs) containing M. alba extract. The stability study of the extract incorporated in the ME was also included. First, pseudo-ternary phase diagrams were constructed using caprylic/capric triglyceride (oil), PEG-8 caprylic/capric glycerides (S), polyglyceryl-3 diisostearate (CoS). Propylene glycol (PG) was used as a cosolvent. Then, the formulations were chosen to incorporate MSE and subjected to stability testing at 4o C, room temperature (RT) and 45o C at 75% RH for 8 weeks. Physical stability of the formulations was assessed by visual observation on the precipitation, phase separation and cloud point. Chemical stability was determined by quantitative analysis of oxyresveratrol using high performance liquid chromatography (HPLC). The results showed that with increasing the ratio of S/CoS, the area of ME existing region in phase diagrams increased. The addition of PG into aqueous phase at ratio 1:1 slightly affected the formation of MEs. Physical stability was not affected by temperature but was influenced by the components of the formulations. However, degradation of the extract was affected by both temperature and components of the formulations. The extract was stable at 4o C and RT. However, at 45o C, it degraded about 16-57%, depending on the components of the formulations. The best ME formulation consisted of 10% caprylic/capric triglyceride, 80% PEG-8 caprylic/capric glycerides and polyglyceryl-3 diisostearate (4:1), and 10% water and PG (1:1).

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 Amorphous Drug-Polymer Salts

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1271
Author(s):  
Xin Yao ◽  
Amy Lan Neusaenger ◽  
Lian Yu
Keyword(s):  
Recent Progress ◽  
Drug Loading ◽  
Salt Formation ◽  
High Drug ◽  
Coated Particles ◽  
Tropical Conditions ◽  
Amorphous Drugs ◽  
Amorphous Drug ◽  
Future Work ◽  
High Drug Loading

Amorphous formulations provide a general approach to improving the solubility and bioavailability of drugs. Amorphous medicines for global health should resist crystallization under the stressful tropical conditions (high temperature and humidity) and often require high drug loading. We discuss the recent progress in employing drug–polymer salts to meet these goals. Through local salt formation, an ultra-thin polyelectrolyte coating can form on the surface of amorphous drugs, immobilizing interfacial molecules and inhibiting fast crystal growth at the surface. The coated particles show improved wetting and dissolution. By forming an amorphous drug–polymer salt throughout the bulk, stability can be vastly enhanced against crystallization under tropical conditions without sacrificing the dissolution rate. Examples of these approaches are given, along with suggestions for future work.

scholarly journals Synthesis and thermal properties of some phenolic resins

2019 ◽  
Vol 7 (1) ◽  
pp. 1-15
Author(s):  
Alshawi F M ◽  
Abdul Razzq K ◽  
Hanoosh W S
Keyword(s):  
Phenol Formaldehyde ◽  
Chemical Properties ◽  
Decomposition Temperature ◽  
Industrial Applications ◽  
Stability Study ◽  
Curing Temperature ◽  
Molar Ratio ◽  
Scanning Calorimetry ◽  
Phenolic Resins ◽  
Physical And Chemical

Introduction: Phenolic resins have been in use since the early twentieth century and are considered the first class of synthetic polymers to achieve commercial success, moreover phenolic resins continue to succeed and attract special interest in a large range of industrial applications such as adhesives, paints, and composites; because of their unique physical and chemical properties. Materials and Methods: Prepolymers resol resins (RR, RH, RP, and RC) were synthesized by the reaction of phenolic compounds (resorcinol, hydroquinone, phloroglucinol, and catechol) respectively, with formaldehyde at molar ratio phenol/ formaldehyde 1/1.5, using sodium hydroxide as a catalyst. These resins were characterized by FTIR. The curing reaction of these resins was evaluated using differential scanning calorimetry (DSC), while the thermal stability study was evaluated using thermogravimetric analysis (TGA). Results and Discussion:From the results showing that these prepolymers have different curing temperatures and curing energy, while the TGA study showed that the cured resins have decomposition temperature more than 300 ºC, and char residue at 650 ºC more than 60%. Conclusions: These resol resins have different gel times (8-55) min, and viscosities (435-350) mpa.s. The curing temperature of these resin obtained from DSC curves was (120, 129, 105 and 127 °C), while the thermal behavior of the cured resins obtained from TGA curves showed that these cured resin have two decomposition temperatures and the rate of decomposition in the order of RC < RR< .

Thermal Properties Analysis of Several N-Alkanes Eutectic Mixtures Applied in Building Envelopes

2012 ◽  
Vol 512-515 ◽  
pp. 3007-3010
Author(s):  
Jing Yu Huang ◽  
Shi Lei Lv ◽  
Chen Xi Zhang ◽  
Zhi Wei Wang
Keyword(s):  
Thermal Properties ◽  
Melting Temperature ◽  
Latent Heat ◽  
Heat Storage ◽  
Eutectic Mixture ◽  
Scanning Calorimetry ◽  
Latent Heat Storage ◽  
Building Envelopes ◽  
Eutectic Mixtures ◽  
Change Material

This study focuses on the preparation, thermal properties of alkanes eutectic mixtures (n-Octadecane/n-Eicosane, n-Octadecane/n-Docosane and n-Heptadecane /n-Eicosane) as candidate phase change material (PCM) for low temperature latent heat storage systems in building envelopes. Their melting temperature and latent heat were tested by Differential scanning calorimetry (DSC). The testing values were closed to calculation values of accepted theory that ensured the reliability of those datas. The results indicated n-Octadecane/n-Docosane eutectic mixture was more promising PCM for buildings in terms of melting temperature (25.3°C) and latent heat values of melting (158.2J/g).

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.

Phase Diagram of the System LaCl3-CaCl2-NaCl

1987 ◽  
Vol 42 (12) ◽  
pp. 1421-1424 ◽  
Author(s):  
K. Igarashi ◽  
H. Ohtani ◽  
J. Mochinaga
Keyword(s):  
Phase Diagram ◽  
Ternary System ◽  
Phase Diagrams ◽  
Binary Systems ◽  
Eutectic Point ◽  
Peritectic Point

The phase diagram of ternary system LaCl3-CaCl2-NaCl has been constructed from the phase diagrams of the three binary systems and of thirteen quasi-binary systems determined by DTA. For the binaries LaCl3-CaCl2 and CaCl2-NaCl eutectic points were observed at 651 °C , 35.1 mol% LaCl3 and at 508 °C , 49.9 mol% NaCl, respectively. For LaCl3-NaCl, a peritectic point besides the eutectic point at 545 °C , 36.1 mol% LaCl3 was found at 690 °C , 57.5 mol%, which is attributable to the formation of the peritectic compound 3 LaCl3 · NaCl. The phase diagram of the ternary system has a ternary eutetic point and a ternary peritectic point due to 3 LaCl3-NaCl, the form er at 462 °C and 12.1 - 3 9 .7 - 4 8 .2 mol% (LaCl3-CaCl2-NaCl) and the latter at 612 °C and 26.9 - 55.1 - 18.0 mol%.

scholarly journals Enhanced Oral Bioavailability of Celecoxib Nanocrystalline Solid Dispersion based on Wet Media Milling Technique: Formulation, Optimization and In Vitro/In Vivo Evaluation

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 328 ◽  
Author(s):  
Zhuang Ding ◽  
Lili Wang ◽  
Yangyang Xing ◽  
Yanna Zhao ◽  
Zhengping Wang ◽  
...  
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Stability Study ◽  
Sprague Dawley ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Celecoxib (CLX), a selective COX-2 inhibitor, is a biopharmaceutics classification system (BCS) class II drug with its bioavailability being limited by thepoor aqueoussolubility. The purpose of this study was to develop and optimize CLX nanocrystalline(CLX-NC) solid dispersion prepared by the wet medium millingtechnique combined with lyophilizationto enhance oral bioavailability. In formulation screening, the resulting CLX-NC usingpolyvinylpyrrolidone (PVP) VA64 and sodiumdodecyl sulfate (SDS) as combined stabilizers showed the minimum particle size and a satisfactory stability. The formulation and preparation processwere further optimized by central composite experimentaldesign with PVP VA64 concentration (X1), SDS concentration (X2) and milling times (X3) as independent factors and particle size (Y1), polydispersity index (PDI, Y2) and zeta potential (Y3) as response variables. The optimal condition was determined as a combination of 0.75% PVP VA64, 0.11% SDS with milling for 90 min.The particle size, PDI and zeta potential of optimized CLX-NC were found to be 152.4 ± 1.4 nm, 0.191 ± 0.012 and −34.4 ± 0.6 mV, respectively. The optimized formulation showed homogeneous rod-like morphology as observed by scanning electron microscopy and was in a crystalline state as determined by differential scanning calorimetry and powder X-ray diffraction. In a storage stability study, optimized CLX-NC exhibited an excellent physical stability during six months’ storage at both the refrigeration and room conditions. In vivo pharmacokinetic research in Sprague-Dawley ratsdisplayed that Cmax and AUC0–∞ of CLX-NC were increased by 2.9 and 3.1 fold, compared with physical mixture. In this study, the screening and optimizing strategy of CLX-NC formulation represents a commercially viable approach forenhancing the oral bioavailability of CLX.

Sign in / Sign up

Export Citation Format

Share Document