Identification of the Glimepiride and Metformin Hydrochloride Physical Interaction in Binary Systems

Glimepiride is often combined with metformin HCl as an oral antidiabetic in type II diabetes mellitus, which provides a complementary and synergistic effect with multiple targets for insulin secretion. Glimepiride includes class II of BCS, which solubility practically insoluble in water but high permeability, which will impact the drug's small bioavailability. In contrast, metformin HCl includes class III of BCS, which has a high solubility in water, but low permeability is absorbed approximately 50-60% in the digestive tract given orally. The co-crystallization method can be used to improve the glimepiride solubility properties and the permeability properties of metformin HCl by interrupting glimepiride with metformin HCl physically. This study aims to identify the physical interactions between glimepiride and metformin HCL using a thermal analysis of Differential Scanning Calorimetry (DSC) and then confirmed by a computational approach. Identifying the physical interactions between glimepiride and metformin HCL was carried out by plotting the melting points generated from the endothermic peaks of the DSC thermogram at various compositions versus the mole ratios of the two were further confirmed by the computational approach using PatchDock. The results of the phase diagram analysis of the binary system between glimepiride and metformin HCl show a congruent pattern, which indicates the formation of co-crystal or molecular compounds at a 1 : 1 mole ratio at 228°C. Computational approach results showed that the interaction between glimepiride and metformin HCl did not form new compounds but heterosinton formation that was stable in molecular dynamics simulations.

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Identification of Physical Interaction in Binary Systems of Acyclovir – Succinic Acid

JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA ◽

10.20473/jfiki.v3i12016.27-31 ◽

2017 ◽

Vol 3 (1) ◽

pp. 27

Author(s):

Agnes Nuniek Winanta ◽

Dwi Setyawan ◽

Siswandono

Keyword(s):

Succinic Acid ◽

Binary Systems ◽

Antiviral Drug ◽

Solvent Evaporation ◽

Crystal Habit ◽

Physical Interaction ◽

Solvent Evaporation Method ◽

Scanning Calorimetry ◽

Pxrd Pattern ◽

Evaporation Method

Background: Acyclovir, a guanosine analogue antiviral drug with low solubility of water. Due to its poor solubility and permeability, causes low oral bioavailability. Objective: The aim of this research is to investigate the physical interaction in binary systems acyclovir-succinic acid (AS). Methods: The msystem was prepared by solvent evaporation method. Results: Thermogram Differential Scanning Calorimetry showed endothermic peaks at 172.68oC (ethanol) and 171.84oC (methanol). The Powder X-Ray Diffraction (PXRD) pattern of AS was different from pure component and physical mixtures. Furthermore, physical characterization showed the binary system of AS have unique crystal habit by polarization microscope. Conclusion: New crystalline phase is formed from the interaction between acyclovir and succinic acid by solvent evaporation method using ethanol and methanol.

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Identification of Physical Interaction in Binary Systems of Acyclovir – Succinic Acid

JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA ◽

10.20473/jfiki.v3i1.4091 ◽

2017 ◽

Vol 3 (1) ◽

pp. 27

Author(s):

Agnes Nuniek Winanta ◽

Dwi Setyawan ◽

Siswandono

Keyword(s):

Succinic Acid ◽

Binary Systems ◽

Antiviral Drug ◽

Solvent Evaporation ◽

Crystal Habit ◽

Physical Interaction ◽

Solvent Evaporation Method ◽

Scanning Calorimetry ◽

Pxrd Pattern ◽

Evaporation Method

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Molecular dynamics simulations on the miscibility and glass transition temperature of PMMA/ATBC binary systems

International Journal of Energetic Materials and Chemical Propulsion ◽

10.1615/intjenergeticmaterialschemprop.2020034939 ◽

2020 ◽

Author(s):

XI Li ◽

Jian Li ◽

Zhu Lin-lin ◽

He Ran-ran ◽

Zong-qun Li ◽

...

Keyword(s):

Molecular Dynamics ◽

Glass Transition ◽

Transition Temperature ◽

Glass Transition Temperature ◽

Molecular Dynamics Simulations ◽

Binary Systems ◽

Dynamics Simulations

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Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

Current Drug Delivery ◽

10.2174/1567201817666200903171124 ◽

2020 ◽

Vol 17 ◽

Author(s):

Akhlesh Kumar Jain ◽

Hitesh Sahu ◽

Keerti Mishra ◽

Suresh Thareja

Keyword(s):

Side Effects ◽

Liver Cancer ◽

Entrapment Efficiency ◽

Xrd Analysis ◽

In Vitro Cytotoxicity ◽

Physical Interaction ◽

Scanning Calorimetry ◽

Starch Nanoparticles

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for site specific delivery. Background: Liver cancer is the third leading cause of death in world and fifth most often diagnosed cancer is the major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and methods: 5-FU loaded JFSSNPs were prepared and optimized formulation had higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. Potential of NPs were studied using in vitro cytotoxicity assay, in vivo kinetic studies and bio-distribution studies. Result and discussion: 5-Fluorouracil loaded NPs had particle size between 336 to 802nm with drug entrapment efficiency was between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of drug in amorphous form. DSC study suggests there was no physical interaction between 5- FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assist selective accumulation of 5-FU in the liver (vs other organs spleen, kidney, lungs and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution and plasma profile studies resulted in significantly higher concentration of 5- Fluorouracil liver suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

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Molecular-Level Investigation of Cycloaliphatic Epoxidised Ionic Liquids as a New Generation of Monomers for Versatile Poly(Ionic Liquids)

Polymers ◽

10.3390/polym13091512 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1512

Author(s):

Baris Demir ◽

Gabriel Perli ◽

Kit-ying Chan ◽

Jannick Duchet-Rumeau ◽

Sébastien Livi

Keyword(s):

Ionic Liquids ◽

Molecular Level ◽

Computational Approach ◽

Polymer Materials ◽

Chemical Structures ◽

Cycloaliphatic Epoxy ◽

Polymer Models ◽

Mechanical Performances ◽

Dynamics Simulations ◽

New Generation

Recently, a new generation of polymerised ionic liquids with high thermal stability and good mechanical performances has been designed through novel and versatile cycloaliphatic epoxy-functionalised ionic liquids (CEILs). From these first promising results and unexplored chemical structures in terms of final properties of the PILs, a computational approach based on molecular dynamics simulations has been developed to generate polymer models and predict the thermo–mechanical properties (e.g., glass transition temperature and Young’s modulus) of experimentally investigated CEILs for producing multi-functional polymer materials. Here, a completely reproducible and reliable computational protocol is provided to design, test and tune poly(ionic liquids) based on epoxidised ionic liquid monomers for future multi-functional thermoset polymers.

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Diethylstilbestrol Modifies the Structure of Model Membranes and Is Localized Close to the First Carbons of the Fatty Acyl Chains

Biomolecules ◽

10.3390/biom11020220 ◽

2021 ◽

Vol 11 (2) ◽

pp. 220

Author(s):

Alessio Ausili ◽

Inés Rodríguez-González ◽

Alejandro Torrecillas ◽

José A. Teruel ◽

Juan C. Gómez-Fernández

Keyword(s):

Membrane Surface ◽

Water Layer ◽

Fatty Acyl ◽

31P Nmr Spectroscopy ◽

Relaxation Rates ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

X Ray ◽

Acyl Chains ◽

Dynamics Simulations

The synthetic estrogen diethylstilbestrol (DES) is used to treat metastatic carcinomas and prostate cancer. We studied its interaction with membranes and its localization to understand its mechanism of action and side-effects. We used differential scanning calorimetry (DSC) showing that DES fluidized the membrane and has poor solubility in DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) in the fluid state. Using small-angle X-ray diffraction (SAXD), it was observed that DES increased the thickness of the water layer between phospholipid membranes, indicating effects on the membrane surface. DSC, X-ray diffraction, and 31P-NMR spectroscopy were used to study the effect of DES on the Lα-to-HII phase transition, and it was observed that negative curvature of the membrane is promoted by DES, and this effect may be significant to understand its action on membrane enzymes. Using the 1H-NOESY-NMR-MAS technique, cross-relaxation rates for different protons of DES with POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) protons were calculated, suggesting that the most likely location of DES in the membrane is with the main axis parallel to the surface and close to the first carbons of the fatty acyl chains of POPC. Molecular dynamics simulations were in close agreements with the experimental results regarding the location of DES in phospholipids bilayers.

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Formulation and development of metformin-loaded microspheres using Khaya senegalensis (Meliaceae) gum as co-polymer

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-020-00139-6 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Chukwuebuka H. Ozoude ◽

Chukwuemeka P. Azubuike ◽

Modupe O. Ologunagba ◽

Sejoro S. Tonuewa ◽

Cecilia I. Igwilo

Keyword(s):

Controlled Release ◽

Sodium Alginate ◽

Release Kinetics ◽

Drug Carrier ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Metformin Hydrochloride ◽

Scanning Calorimetry ◽

Khaya Senegalensis

Abstract Background Khaya gum is a bark exudate from Khaya senegalensis (Maliaecae) that has drug carrier potential. This study aimed to formulate and comparatively evaluate metformin-loaded microspheres using blends of khaya gum and sodium alginate. Khaya gum was extracted and subjected to preformulation studies using established protocols while three formulations (FA; FB and FC) of metformin (1% w/v)-loaded microspheres were prepared by the ionic gelation method using 5% zinc chloride solution as the cross-linker. The formulations contained 2% w/v blends of khaya gum and sodium alginate in the ratios of 2:3, 9:11, and 1:1, respectively. The microspheres were evaluated by scanning electron microscopy, Fourier transform-infrared spectroscopy, differential scanning calorimetry, entrapment efficiency, swelling index, and in vitro release studies. Results Yield of 28.48%, pH of 4.00 ± 0.05, moisture content (14.59% ± 0.50), and fair flow properties (Carr’s index 23.68 ± 1.91 and Hausner’s ratio 1.31 ± 0.03) of the khaya gum were obtained. FTIR analyses showed no significant interaction between pure metformin hydrochloride with excipients. Discrete spherical microspheres with sizes ranging from 1200 to 1420 μm were obtained. Drug entrapment efficiency of the microspheres ranged from 65.6 to 81.5%. The release of the drug from microspheres was sustained for the 9 h of the study as the cumulative release was 62% (FA), 73% (FB), and 80% (FC). The release kinetics followed Korsmeyer-Peppas model with super case-II transport mechanism. Conclusion Blends of Khaya senegalensis gum and sodium alginate are promising polymer combination for the preparation of controlled-release formulations. The blend of the khaya gum and sodium alginate produced microspheres with controlled release properties. However, the formulation containing 2:3 ratio of khaya gum and sodium alginate respectively produced microspheres with comparable controlled release profiles to the commercial brand metformin tablet.

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Structural stability of CmTin microclusters and nanoparticles: Molecular–dynamics simulations

Computing Letters ◽

10.1163/157404005776611321 ◽

2005 ◽

Vol 1 (4) ◽

pp. 204-209

Author(s):

O.B. Malcıoğlu ◽

Ş. Erkoç

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Binary Systems ◽

Minimum Energy ◽

Potential Energy Function ◽

Md Simulations ◽

Atomic Interactions ◽

Dynamics Simulations ◽

Three Body ◽

Initial Geometry

The minimum energy structures of CmTin microclusters and nanoparticles have been investigated theoretically by performing molecular–dynamics (MD) simulations. Selected crystalline and completely random initial geometries are considered. The potential energy function (PEF) used in the calculations includes two– and three–body atomic interactions for C-Ti binary systems. Molecular–dynamics simulations have been performed at 1 K and 300 K. It has been found that initial geometry has a very strong influence on relaxed geometry

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CHARACTERISATION OF INCLUSION COMPLEXES BETWEEN BIFONAZOLE AND DIFFERENT CYCLODEXTRINS IN SOLID AND SOLUTION STATE

Macedonian Journal of Chemistry and Chemical Engineering ◽

10.20450/mjcce.2017.1031 ◽

2017 ◽

Vol 36 (1) ◽

pp. 81 ◽

Cited By ~ 6

Author(s):

Hajnal Kelemen ◽

Angella Csillag ◽

Gabriel Hancu ◽

Blanka Székely-Szentmiklósi ◽

Ibolya Fülöp ◽

...

Keyword(s):

Inclusion Complexes ◽

Binary Systems ◽

Pharmaceutical Formulations ◽

2D Nmr ◽

Local Drug Delivery ◽

Stable Complex ◽

Resonance Spectroscopy ◽

Scanning Calorimetry ◽

2D Nmr Spectroscopy ◽

Major Drawback

The aim of this study is to confirm the formation of inclusion complexes between bifonazole (BFZ) and different cyclodextrin (CD) derivatives. Bifonazole, an imidazole antifungal derivative,is a very hydrophobic compound, which is a major drawback in obtaining topical pharmaceutical formulations with optimal bioavailability. Cyclodextrins may increase local drug delivery by enhancing the drug release and/or permeation. The binary systems between bifonazole and cyclodextrins were prepared in two molar ratios by physical-mixture methods.The physicochemical properties of these complexes were studied by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR) methods. Results showed favourable molecular interaction between the components, in solid state and in solution. 1H NMR -CD titrations and molecular modelling study showed that the most stable complex was obtained when using γ-CD. The Job’s method and 2D NMR spectroscopy sustain the 2:1 stoichiometry of the BFZ:γ-CD complex.

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