scholarly journals Supersaturation Potential of Amorphous Active Pharmaceutical Ingredients after Long-Term Storage

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2731 ◽  
Author(s):  
Khadijah Edueng ◽  
Denny Mahlin ◽  
Johan Gråsjö ◽  
Olivia Nylander ◽  
Manish Thakrani ◽  
...  
Keyword(s):  
Solid State ◽  
Crystallization Kinetics ◽  
Physical Aging ◽  
Area Under The Curve ◽  
Crystallization Rate ◽  
Active Pharmaceutical Ingredients ◽  
Scanning Calorimetry ◽  
Supersaturation Ratio ◽  
Pharmaceutical Ingredients ◽  
Spray Dried

This study explores the effect of physical aging and/or crystallization on the supersaturation potential and crystallization kinetics of amorphous active pharmaceutical ingredients (APIs). Spray-dried, fully amorphous indapamide, metolazone, glibenclamide, hydrocortisone, hydrochlorothiazide, ketoconazole, and sulfathiazole were used as model APIs. The parameters used to assess the supersaturation potential and crystallization kinetics were the maximum supersaturation concentration (Cmax,app), the area under the curve (AUC), and the crystallization rate constant (k). These were compared for freshly spray-dried and aged/crystallized samples. Aged samples were stored at 75% relative humidity for 168 days (6 months) or until they were completely crystallized, whichever came first. The solid-state changes were monitored with differential scanning calorimetry, Raman spectroscopy, and powder X-ray diffraction. Supersaturation potential and crystallization kinetics were investigated using a tenfold supersaturation ratio compared to the thermodynamic solubility using the µDISS Profiler. The physically aged indapamide and metolazone and the minimally crystallized glibenclamide and hydrocortisone did not show significant differences in their Cmax,app and AUC when compared to the freshly spray-dried samples. Ketoconazole, with a crystalline content of 23%, reduced its Cmax,app and AUC by 50%, with Cmax,app being the same as the crystalline solubility. The AUC of aged metolazone, one of the two compounds that remained completely amorphous after storage, significantly improved as the crystallization kinetics significantly decreased. Glibenclamide improved the most in its supersaturation potential from amorphization. The study also revealed that, besides solid-state crystallization during storage, crystallization during dissolution and its corresponding pathway may significantly compromise the supersaturation potential of fully amorphous APIs.

The non-isothermal crystallization behavior of polyamide 6 and polyamide 6/HDPE/MAH/L-101 composites

2019 ◽  
Vol 39 (2) ◽  
pp. 124-133 ◽  
Author(s):  
Bingxiao Liu ◽  
Guosheng Hu ◽  
Jingting Zhang ◽  
Zhongqiang Wang
Keyword(s):  
Crystallization Kinetics ◽  
Isothermal Crystallization ◽  
Crystallization Behavior ◽  
Isothermal Condition ◽  
Crystallization Rate ◽  
Polyamide 6 ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Analysis And Design ◽  
Processing Techniques

AbstractStudy of the crystallization kinetics is particularly necessary for the analysis and design of processing operations, especially the non-isothermal crystallization behavior, which is due to the fact that most practical processing techniques are carried out under non-isothermal conditions. The non-isothermal crystallization behaviors of polyamide 6 (PA6) and PA6/high-density polyethylene/maleic anhydride/2,5-dimethyl-2,5-di(tert-butylperoxy)hexane (PA6/HDPE/MAH/L-101) composites were investigated by differential scanning calorimetry (DSC). The crystallization kinetics under non-isothermal condition was analyzed by the Jeziorny and Mo equations, and the activation energy was determined by the Kissinger and Takhor methods. The crystal structure and morphology were analyzed by wide-angle X-ray diffraction (WXRD) and polarized optical microscopy (POM). The results indicate that PA6/HDPE/MAH/L-101 has higher crystallization temperature and crystallization rate, which is explained as due to its heterogeneous nuclei.

35Cl solid-state NMR of HCl salts of active pharmaceutical ingredients: structural prediction, spectral fingerprinting and polymorph recognition

CrystEngComm ◽  
2014 ◽  
Vol 16 (31) ◽  
pp. 7334-7356 ◽  
Author(s):  
Marcel Hildebrand ◽  
Hiyam Hamaed ◽  
Andrew M. Namespetra ◽  
John M. Donohue ◽  
Riqiang Fu ◽  
...  
Keyword(s):  
Solid State ◽  
Plane Wave ◽  
Dft Calculations ◽  
First Principles ◽  
Solid State Nmr ◽  
Active Pharmaceutical Ingredients ◽  
Structural Prediction ◽  
Pharmaceutical Ingredients

A series of HCl salts of active pharmaceutical ingredients (APIs) have been characterized via35Cl solid-state NMR (SSNMR) spectroscopy and first-principles plane-wave DFT calculations of 35Cl NMR interaction tensors.

Chemometric approaches to low-content quantification (LCQ) in solid-state mixtures using Raman mapping spectroscopy

2017 ◽  
Vol 9 (44) ◽  
pp. 6293-6301 ◽  
Author(s):  
Boyan Li ◽  
Yannick Casamayou-Boucau ◽  
Amandine Calvet ◽  
Alan G. Ryder
Keyword(s):  
Solid State ◽  
Pharmaceutical Manufacturing ◽  
Active Pharmaceutical Ingredients ◽  
Raman Mapping ◽  
Pharmaceutical Ingredients

The low-content quantification (LCQ) of active pharmaceutical ingredients or impurities in solid mixtures is important in pharmaceutical manufacturing and analysis.

scholarly journals Combined Effects of Cellulose Nanofiber Nucleation and Maleated Polylactic Acid Compatibilization on the Crystallization Kinetic and Mechanical Properties of Polylactic Acid Nanocomposite

Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3226
Author(s):  
Siti Shazra Shazleen ◽  
Lawrence Yee Foong Ng ◽  
Nor Azowa Ibrahim ◽  
Mohd Ali Hassan ◽  
Hidayah Ariffin
Keyword(s):  
Mechanical Properties ◽  
Tensile Strength ◽  
Polylactic Acid ◽  
Crystallization Kinetics ◽  
Crystallization Kinetic ◽  
Crystallization Rate ◽  
Combined Effects ◽  
Dsc Analysis ◽  
Scanning Calorimetry ◽  
Isothermal Crystallization Kinetics

This work investigated the combined effects of CNF nucleation (3 wt.%) and PLA-g-MA compatibilization at different loadings (1–4 wt.%) on the crystallization kinetics and mechanical properties of polylactic acid (PLA). A crystallization kinetics study was done through isothermal and non-isothermal crystallization kinetics using differential scanning calorimetry (DSC) analysis. It was shown that PLA-g-MA had some effect on nucleation as exhibited by the value of crystallization half time and crystallization rate of the PLA/PLA-g-MA, which were increased by 180% and 172%, respectively, as compared to neat PLA when isothermally melt crystallized at 100 °C. Nevertheless, the presence of PLA-g-MA in PLA/PLA-g-MA/CNF3 nanocomposites did not improve the crystallization rate compared to that of uncompatibilized PLA/CNF3. Tensile strength was reduced with the increased amount of PLA-g-MA. Contrarily, Young’s modulus values showed drastic increment compared to the neat PLA, showing that the addition of the PLA-g-MA contributed to the rigidity of the PLA nanocomposites. Overall, it can be concluded that PLA/CNF nanocomposite has good performance, whereby the addition of PLA-g-MA in PLA/CNF may not be necessary for improving both the crystallization kinetics and tensile strength. The addition of PLA-g-MA may be needed to produce rigid nanocomposites; nevertheless, in this case, the crystallization rate of the material needs to be compromised.

scholarly journals Enhancement of Solubility BCS Class II and IV Pharmaceuticals by Liqusolid Technique: A review

2020 ◽  
Vol 2 (2) ◽  
pp. 77
Author(s):  
Dwi Retno Sari ◽  
Yoga Windhu Wardhana ◽  
Taofik Rusdiana
Keyword(s):  
Contact Angle ◽  
Drug Release ◽  
Manufacturing Industry ◽  
Fourier Transforms ◽  
Class Ii ◽  
Production Costs ◽  
Active Pharmaceutical Ingredients ◽  
Scanning Calorimetry ◽  
Pharmaceutical Ingredients ◽  
Volatile Solvents

Many techniques can be used to improve drug solubility, which is the development of the liquisolid technique. This technique has a mechanism for increasing the surface area of the drug as well as wetting from the addition of non-volatile solvents resulting in a lower surface tension and contact angle, so the solubility and drug release very increases. Liquisolid tablets show a lower contact angle compared to the conventional tablets. The liquisolid technique approach is also promising because the process is simple in making low production costs and allows the manufacturing industry, including non-volatile solvents, fillers, dryers, and disintegrants. Liquisolid characterized by specific instruments such as powder x-ray diffraction (PXRD), Fourier transforms infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscope (SEM). Several liquisolid techniques are described in this review. The liquisolid technique is proven and able to change the physicochemical properties of active pharmaceutical ingredients, especially the solubility, drug release, and stability of the formula so that this technique can be a solution for class II and IV BCS pharmaceutical active drug classes.Keywords: Active Pharmaceutical Ingredients, Contact Angle, Solubility, Drug Release, Stability, Liquisolid Technique

scholarly journals Raman and Terahertz Spectroscopic Investigation of Cocrystal Formation Involving Antibiotic Nitrofurantoin Drug and Coformer 4-aminobenzoic Acid

2016 ◽  
Author(s):  
Yong Du ◽  
Qiang Cai ◽  
Jiadan Xue ◽  
Qi Zhang
Keyword(s):  
Solid State ◽  
Spectroscopic Techniques ◽  
Vibrational Modes ◽  
Active Pharmaceutical Ingredients ◽  
Aminobenzoic Acid ◽  
Parent Materials ◽  
Pharmaceutical Development ◽  
Pharmaceutical Ingredients ◽  
Pharmaceutical Cocrystal ◽  
Rich Information

Cocrystallizaiton could improve most physicochemical properties of specific active pharmaceutical ingredients, which has great potential in pharmaceutical development. In this study, the cocrystal of nitrofurantoin and 4-aminobenzoic acid was prepared with solid-state (solvent-free or green-chemistry) grinding approach, and the above cocrystal has been characterized by Raman and terahertz vibrational spectroscopic techniques. Spectral results show that the vibrational modes of the cocrystal within the whole spectral region are different from those of the corresponding parent materials. The dynamic process of such pharmaceutical cocrystal formation has also been monitored directly with Raman spectra. These results offer us unique means for characterizing the cocrystal conformation from molecule-level and also provide us rich information about the reaction dynamic of cocrystal formation within pharmaceutical fields.

scholarly journals Maltose-mediated long-term stabilization of freeze- and spray- dried forms of bovine and porcine hemoglobin

2019 ◽  
Vol 84 (10) ◽  
pp. 1105-1117 ◽  
Author(s):  
Ivana Drvenica ◽  
Ana Stancic ◽  
Ana Kalusevic ◽  
Smilja Markovic ◽  
Jelena Dragisic-Maksimovic ◽  
...  
Keyword(s):  
Solid State ◽  
Heme Iron ◽  
Deficiency Anemia ◽  
Scanning Calorimetry ◽  
Freeze Dried ◽  
Methemoglobin Formation ◽  
The Stability ◽  
Porcine Hemoglobin ◽  
Spray Dried

Slaughterhouse blood represents a valuable source of hemoglobin, which can be used in the production of heme-iron based supplements for the prevention/treatment of iron-deficiency anemia. In order to obtain a stable solid-state formulation, the effect of maltose addition (30 %) on the stability and storage of bovine and porcine hemoglobin in powders obtained by spray and freeze-drying (without maltose: Hb; with maltose: HbM) were investigated. Differential scanning calorimetry of spray- and freeze-dried powders indicated satisfying quality of the formulation prepared with maltose on dissolving back into solution. After two-year storage at room temperature (20?5?C) in solid forms, protected from moisture and light, rehydrated spray- and freeze-dried HbM were red, while Hb were brown. Dynamic light scattering showed the presence of native hemoglobin monomers in rehydrated spray- and freeze-dried HbM, but their agglomerates in Hb samples. UV?Vis spectrophotometry confirmed an absence of significant hemoglobin denaturation and methemoglobin formation in HbM freeze-dried powders. In spray-dried HbM, an increased level of methemoglobin was detected. The results confirmed the stabilizing effect of maltose, and suggested its use in the production of long-term stable solid-state formulations of hemoglobin, along with drying processes optimization.

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