Characterization of venlafaxine hydrochloride and compatibility studies with pharmaceutical excipients

The thermal analytical study of venlafaxine hydrochloride, a third generation antidepressant, was investigated using thermogravimetry (TG) and differential scanning calorimetry (DSC). The DSC curves have shown a sharp endothermic event at 211 °C and TG demonstrated a single stage of mass loss between 254 and 283 °C. Solid-state characterization was carried out by DRIFT, SEM, and XRPD demonstrating the drug physicochemical properties including crystallinity. Drug-excipient compatibility studies investigated by DSC have shown a possible physical interaction of the drug with magnesium stearate, microcrystalline cellulose and starch. Nevertheless, these results where not confirmed by DRIFT and SEM analyses.     

Characterization of the effect of REC on the compatibility of PHBH and PLA

This study reports the compatibility of the biobased polymers poly(3-hydroxybutyrate-co-3- -hydroxyhexanoate) (PHBH) and poly(lactic acid) (PLA), as well as the effect of the addition of a reactive epoxy compatibilizer (REC) to the PHBH/PLA blend. The chemical structure, thermal performance, surface morphology and mechanical properties of the blends were measured using fourier transform infrared spectroscopy, differential scanning calorimetry, dynamic thermo-mechanical analysis, thermogravimetric analysis, scanning electron microscopy, and impact and tensile testing.PHBH and PLA were partially compatible, and a PHBH/PLA mass ratio of 80:20 was selected for evaluation with an REC. The REC decreased the difference between the glass-transition temperatures of PHBH and PLA, decreased the particle size of the dispersed phase of the PHBH/PLA blend and produced uniform particle distribution. Moreover, the REC improved the elongation at break and impact strength of the PHBH/PLA blend. These results show that the addition of an REC improves the compatibility of PHBH and PLA.     

Characterization of nanostructure and cell compatibility of polyaniline films with different dopant acids

Polyaniline (PANi) films were prepared by direct polymerizing deposition with four different kinds of acids as dopants or were prepared by a casting method on the surface of a polytetrafluoroethylene substrate. The properties of PANi films were characterized using atomic force microscopy, electrical conductivity measurements, and water contact angle measurements. Unlike the casting PANi film, experimental results indicated that the synthesized PANi films had a similar nanostructure as that of average nanoparticles (approximate diameter of 30-50 nm). To investigate the potential usefulness of PANi films in biomedical applications, we also studied their biocompatibility through the adhesion and proliferation properties of PC-12 pheochromocytoma cells. All the films were found to be biocompatible and allowed cell attachment and proliferation. However, the synthesized films have a much higher ability for cell adhesion than the casting film. After 4 days of culture on different PANi films, the cells formed more confluent monolayers on the synthesized PANi films than on the casting films. These results demonstrate that the PANi films could be used to culture neurotic cells and that their surface architecture on the nanoscale may affect cell function such as attachment and proliferation.     

Characterization and compatibility of dry extract from Annona muricata L. and pharmaceutical excipients

Journal of Thermal Analysis and Calorimetry - The aim of this study was to characterize and evaluate the compatibility of the dry extract (DE) of leaves of Annona muricata L. with pharmaceutical...     

NMR spectroscopic study of the inclusion complex of desloratadine with β-cyclodextrin in solution

Desloratadine (DES) is an antihistamine used in the treatment of allergies and chronic urticaria. ¹H NMR spectroscopic study of varying ratios of DES and β-Cyclodextrin (β-CD) in D₂O suggests the formation of a 1:1 inclusion complex formed by the penetration of Cl-substituted aromatic ring into the β-CD cavity. The stoichiometry and binding constant of the complex were determined by Scott’s method.     

Synthesis and biological evaluation of novel derivatives of desloratadine

Series of novel derivatives of desloratadine designed as arginine vasopressin receptor antagonists were synthesized and structurally characterized by melting points,~1H NMR and HRMS.Their in vivo diuretic activities were evaluated on rats,and several target compounds showed promising diuretic results, especially compounds 8,18,27 and 31.Further in vitro bonding assay and cAMP assay showed that these compounds had a higher affinity to vasopressin V2 receptor than VI a receptor.Our studies indicated that desloratadine may be an active substructure for novel arginine vasopressin receptor antagonist development.     

Stability and compatibility study on enalapril maleate using thermoanalytical techniques

This paper demonstrates the application of thermal analysis in compatibility and stability studies between an ACE inhibitor (enalapril maleate) and excipients. The results have helped to elucidate the reason of a stability problem observed during the storage of enalapril maleate tablets. Incompatibility between enalapril maleate and colloidal silicon dioxide was detected. Besides, it was confirmed that the reaction between enalapril maleate and NaHCO₃ increases the thermal stability of the drug. This study supports the importance of using thermoanalytical methods in the development of pharmaceuticals.     

Physicochemical characterization and compatibility study of roflumilast with various pharmaceutical excipients

Journal of Thermal Analysis and Calorimetry - To rich flavor additive species of pyrazines, two new compounds of 3,6-dimethyl-2,5-pyrazinedicarboxylic acid 1-octen-3-yl ester (DMPOE) and...     

Synthesis,characterization, and compatibility study of acetylated starch with lamivudine

In this study, highly substituted starch acetate was prepared by reaction with native moth bean starch and acetic anhydride. Physicochemical characterization of this modified starch was done using scanning electron microscopy, X-ray diffraction, and thermogravimetric analysis. Their formation was confirmed by titrimetric analysis and highest degree of substitution was observed with a value of 2.35. The synthesized modified starch was further studied for compatibility with model drug lamivudine using differential scanning calorimetry and isothermal stress testing for its controlled release tablet formulation.     

Thermodynamical study on pressure-induced compatibility in UCST polymer-containing mixtures

The pressure effect on polymer-containing systems has been intensely studied in the past decades, and there has been increased interest in the effects of pressure on the miscibility of polymers[1—6]. One reason is the realization that such pressure effects could be important in many situations where such blends are used, e.g. when mixing a blend in an extruder or in forming arti-cles from a blend by injection molding. Another is the thermodynamics of typical polymer blends that are understood…     

A study of macroderm a and macroderm L monolayers and their two-dimensional compatibility

 Spread monolayers of two new skin permeation enhancers, MacroDerm A and MacroDerm L were investigated at the water/air interface as a function of temperature and of subphase composition. Both components did not seem to be markedly affected by changes in ionic strength and by the presence of metal ions in the subphase. The two-dimensional binary system MacroDerm A –MacroDerm L was also studied at the water/air interface at 298 K on pure water subphase. The behavior of surface areas, surface compressional moduli and collapse pressure as a function of molar ratios of components shows that MacroDerm A and MacroDerm L are miscible. Received: 17 December 1996 Accepted: 5 March 1997     

Viscometric study on the compatibility of some water-soluble polymer-polymer mixtures

Dilute solution viscosity behavior of three water-soluble polymer mixtures has been studied at 20 °C. The ternary systems assayed are distilled water/sodium carboxymethylcellulose (CMC)/polyacrylamide (PAM), distilled water/methylcellulose (MC)/CMC, and distilled water/polyvinylpyrrolidone (PVP)/MC. The intrinsic viscosity and the viscometric interaction parameters have been determined for the binary (distilled water/polymer) and ternary (distilled water/polymer1/polymer2) systems. Degree of compatibility of these polymer systems was estimated on the basis of five criteria: (i) the sign of Δb_m, (ii) the sign of Δb_m^′, (iii) the sign of Δ[η]_m, (iv) sign of thermodynamic parameter α, and (v) the sign of modified thermodynamic parameter β. Based on the sign convention involved in these criteria, compatibility/miscibility was observed in CMC/PAM and MC/CMC systems and incompatibility/immiscibility in PVP/MC system. The FTIR analyses also support the obtained results. The miscibility/compatibility of all these systems is in accordance with the interactions between the unlike polymer chains rather than the polymer-solvent interactions.     

Synthesis and properties of polycyanoethylmethylsiloxane polyurea urethane elastomers: A study of segmental compatibility

A series of polyurea urethane block polymers based on either aminopropyl-terminated polycyanoethylmethylsiloxane (PCEMS) soft segments or soft segment blends of PCEMS and polytetramethylene oxide (PTMO) were synthesized. The hard segments consisted of 4,4′-methylenediphenylene diisocyanate (MDI) chain-extended with 1,4-butanediol. The hard segment content varied from 11 to 36%, whereas the PTMO weight fraction in the soft segment blends varied from 0.1 to 0.9. The cyanoethyl side group concentration was also varied during the synthesis of the PCEMS oligomer. The morphology and properties of these polymers were studied by differential scanning calorimetry, infrared spectroscopy, dynamic mechanical and tensile testing, and small-angle x-ray scattering. These materials exhibited microphase separation of the hard and soft segments; however, attaching polar cyanoethyl side groups along the apolar siloxane chains promoted phase mixing in comparison with polydimethylsiloxane-based polyurethanes. The increased phase mixing is postulated to lead to improved interfacial adhesion and thus can account for the observed improvement in ultimate tensile properties compared with polydimethylsiloxane-based polyurethanes. Both hard segment content and cyanoethyl concentration are important factors governing the morphological and tensile properties of these polymers.     

Thermal behaviour, compatibility study and decomposition kinetics of glimepiride under isothermal and non-isothermal conditions

In the present work, the thermal decomposition of glimepiride (sulfonylurea hypoglycemic agent) was studied using differential scanning calorimetry (DSC) and thermogravimetry/derivative thermogravimetry (TG/DTG). Isothermal and non-isothermal methods were employed to determine kinetic data of decomposition process. The physical chemical properties and compatibilities of several commonly used pharmaceutical excipients (glycolate starch, microcrystalline cellulose, stearate, lactose and Plasdone®) with glimepiride were evaluated using thermoanalytical methods. The 1:1 physical mixtures of these excipients with glimepiride showed physical interaction of the drug with Mg stearate, lactose and Plasdone®. On the other hand, IR results did not evidence any chemical modifications. From isothermal experiments, activation energy (E _a) can be obtained from slope of lnt vs. 1/T at a constant conversion level. The average value of this energy was 123 kJ mol^–1. For non-isothermal method E _a can be obtained from plot of logarithms of heating rates, as a function of inverse of temperature, resulting a value of 157 and 150 kJ mol^–1, respectively, in air and N₂ atmosphere, from the first stage of thermal decomposition.     

Form I of desloratadine,a tricyclic anti­histamine

The title compound [systematic name: 8‐chloro‐11‐(piperidin‐4‐yl­idene)‐6,11‐dihydro‐5H‐benzo[4,5]cyclo­hepta­[2,1‐b]pyridine], C₁₉H₁₉ClN₂, was crystallized from ethyl acetate. The inter­esting feature of the reported structure is that it does not contain any strong hydrogen bonds, although the mol­ecule contains a secondary NH group, which is a good hydrogen‐bond donor.     

Application of DSC and NIRS to study the compatibility of metronidazole with different pharmaceutical excipients

The purpose of the present work was to study the compatibility of metronidazole with different pharmaceutical excipients (hydroxypropyl methylcellulose, poly(ethylene oxide), microcrystalline cellulose, dicalcium phosphate dihydrate, and anhydrous dicalcium phosphate) using differential scanning calorimetry and diffuse reflectance spectroscopy. Dicalcium phosphate dihydrate was the only excipient that showed interaction with metronidazole even before storage. Changes referring to a possible transition to dihydrate form were observed in the thermal curves of anhydrous dicalcium phosphate after four weeks of storage. Although dicalcium phosphate dihydrate can be replaced by the anhydrous form in pharmaceutical formulations, the observed transition might negatively influence the stability of dosage forms.     

Spectrophotometric, spectrofluorometric and HPLC determination of desloratadine in dosage forms and human plasma

Four sensitive, simple and specific methods were developed for the determination of desloratadine (DSL), a new antihistaminic drug in pharmaceutical preparations and biological fluids. Methods I and II are based on coupling DSL with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in borate buffer of pH 7.6 where a yellow colored reaction product was obtained and measured spectrophotometrically at 485 nm (Method I). The same product could be measured spectrofluorometrically at 538 nm after excitation at 480 nm (Method II). Methods III and IV, on the other hand, involved derivatization of DSL with 2,4-dinitrofluorobenzene (DNFB) in borate buffer of pH 9.0 producing a yellow colored product that absorbs maximally at 375 nm (Method III). The same derivative was determined after separation adopting HPLC (Method IV). The separation was performed on a column packed with cyanopropyl bonded stationary phase equilibrated with a mobile phase composed of acetonitrile-water (60 : 40, v/v) at a flow rate of 1.0 ml min(-1) with UV detection at 375 nm. The calibration curves were linear over the concentration ranges of 0.5-6, 0.02-0.4, 1-10 and 1-30 microg ml(-1) for Methods I, II, III and IV, respectively. The lower detection limits (LOD) were 0.112, 0.004, 0.172 and 0.290 microg ml(-1), respectively, for the four methods. The limits of quantification (LOQ) were 0.340, 0.012, 0.522 and 0.890 microg ml(-1) for Methods I, II, III and IV, respectively. The proposed methods were applied to the determination of desloratadine in its tablets and the results were in agreement with those obtained using a reference method. Furthermore, the spectrofluorometric method (Method II) was extended to the in-vitro determination of the drug in spiked human plasma, with a mean percentage recovery (n=4) of 99.7+/-3.54. Interference arising from endogenous amino acids has been overcome using solid phase extraction. The proposed methods are highly specific for determination of DSL in the presence of the parent drug loratadine. A proposal for the reaction pathways is postulated.     

Characterization and study of photochromism of hydroxylated polyazomethines

Polymers having a photochromic and/or thermochromic backbone have been synthesized by the condensation of bissalicylaldehydes with diamines. Photochromic activity was studied for hydroxylated polazomethines (HPAM) in the solid state and as thin films at room temperature, −75 and −180°. HPAM showed thermochromic behaviour but not photochromism. The lack of photochromic activity is attributed to the polymeric chain and the moieties attached to the azomethine groups which may increase the potential energy barrier and thus prevent the formation of trans-keto photoproduct.     

A sensitive spectrophotometric method for the determination of desloratadine in tablets

A simple, rapid, and sensitive visible spectrophotometric method was developed, for the first time, for analysis of desloratadine (DE) in tablets. The method is based on the deep-blue colored TCNQ*- radical anion formed by interaction of the drug (n-donor) with 7,7,8,8-tetracyanoquinodimethane (TCNQ, pi-acceptor) in acetonitrile at ambient temperature. Optimum conditions for the reaction were investigated, absorbances were read at 843 nm, and the linearity range for concentrations of DE was found to be 1.5-13 microg/mL. The reaction product remains stable up to 8 h when kept at room temperature in the dark. The developed method was validated and successfully applied to the determination of DE in tablets. The tablets were also analyzed with a column liquid chromatography method reported in literature. The results from both methods were statistically compared by t- and F-tests. No significant difference was found for the means and standard deviations at 95% confidence level. Accuracy was examined through recovery studies. Being very simple and reliable, the method can be recommended for routine quality control analysis of DE in tablets.