Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems—Instrumental Screening

The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under ambient conditions and thermal stress was evaluated. Since LTSS is a synthetic hormone with a narrow therapeutic index, the interactions of LTSS with excipients can lead to a drastic diminution of therapeutic activity. Ten commonly used pharmaceutical excipients with different roles in solid formulations were chosen as components for binary mixtures containing LTSS, namely, starch, anhydrous lactose, D-mannitol, D-sorbitol, gelatin, calcium lactate pentahydrate, magnesium stearate, methyl 2-hydroxyethyl cellulose (Tylose), colloidal SiO2 (Aerosil) and talc. As investigational tools, universal attenuated total reflectance- Fourier transform infrared spectroscopy UATR-FTIR spectroscopy and thermal analysis were chosen and used as follows: UATR-FTIR spectra were drawn up for samples kept under ambient conditions, while thermoanalytical tools (TG/DTG/HF data) were chosen to evaluate the inducing of interactions during thermal stress. The corroboration of instrumental results led to the conclusion that LTSS is incompatible with lactose, mannitol and sorbitol, and these excipients should not be considered in the development of new generic solid formulations.

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Solid State Stability and Preformulation Studies for Acetylcholinesterase Inhibitor Drug Tacrine

Timisoara Medical Journal ◽

10.35995/tmj20200104 ◽

2020 ◽

Vol 2020 (1) ◽

pp. 1

Author(s):

Denisa Circioban ◽

Ionuț Ledeți ◽

Gabriela Vlase ◽

Titus Vlase ◽

Adriana Ledeți

Keyword(s):

Thermal Stress ◽

Carboxymethyl Cellulose ◽

Acetylcholinesterase Inhibitor ◽

Magnesium Stearate ◽

Calcium Lactate ◽

Sodium Carboxymethyl Cellulose ◽

Ambient Conditions ◽

Thermally Induced ◽

Inhibitor Drug ◽

Anhydrous Lactose

In this paper, the acetylcholinesterase inhibitor drug tacrine was investigated by two complementary instrumental techniques, namely infrared spectroscopy and thermal analysis, as pure drug and in solid binary mixtures with nine excipients frequently used in the pharmaceutical industry, namely starch, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30, fumed silica (Aerosil), talc, anhydrous lactose, magnesium stearate, mannitol and calcium lactate pentahydrate. The corroboration of obtained data by the two complementary methods confirmed the incompatibility of this drug with anhydrous lactose, mannitol, magnesium stearate and calcium lactate under both ambient conditions and thermal stress, and thermally induced interactions between tacrine and silica. In the development of new generic solid formulations, four of the investigated excipients (i.e., starch, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30 and talc) can be used, since they are compatible with tacrine under ambient conditions as well as under thermal stress.

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Advances and Limitations of Antibody Drug Conjugates for Cancer

Biomedicines ◽

10.3390/biomedicines9080872 ◽

2021 ◽

Vol 9 (8) ◽

pp. 872

Author(s):

Candice Maria Mckertish ◽

Veysel Kayser

Keyword(s):

Therapeutic Index ◽

Narrow Therapeutic Index ◽

Antibody Drug Conjugates ◽

Drug Conjugates ◽

The Stability ◽

Drug Antibody Ratio ◽

Chemotherapy Agents ◽

The Impact ◽

Antibody Ratio ◽

Antibody Drug

The popularity of antibody drug conjugates (ADCs) has increased in recent years, mainly due to their unrivalled efficacy and specificity over chemotherapy agents. The success of the ADC is partly based on the stability and successful cleavage of selective linkers for the delivery of the payload. The current research focuses on overcoming intrinsic shortcomings that impact the successful development of ADCs. This review summarizes marketed and recently approved ADCs, compares the features of various linker designs and payloads commonly used for ADC conjugation, and outlines cancer specific ADCs that are currently in late-stage clinical trials for the treatment of cancer. In addition, it addresses the issues surrounding drug resistance and strategies to overcome resistance, the impact of a narrow therapeutic index on treatment outcomes, the impact of drug–antibody ratio (DAR) and hydrophobicity on ADC clearance and protein aggregation.

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Atmospherically Stable Silver Nanowire/Hydroxyethyl Cellulose Films and their Application in Flexible Transparent Touch Screen

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.821.401 ◽

2019 ◽

Vol 821 ◽

pp. 401-406 ◽

Cited By ~ 1

Author(s):

Nathaniel De Guzman ◽

Mary Donnabelle L. Balela

Keyword(s):

Indium Tin Oxide ◽

Silver Nanowires ◽

Touch Screen ◽

Silver Nanowire ◽

Hydroxyethyl Cellulose ◽

Protective Agent ◽

Ambient Conditions ◽

Suitable Material ◽

Cellulose Films ◽

The Stability

Silver nanowires (AgNWs) has been extensively studied to replace indium tin oxide as a suitable material for transparent conducting films (TCEs) The networks of nanowires however are prone to degradation due to corrosion when exposed to ambient conditions. In this study, high aspect ratio AgNWs were synthesized with an improved polyol method by varying the reaction temperatures in the nucleation and growth stage. Solutions of AgNWs were deposited on polymer substrates and were exposed to ambient laboratory conditions for several days and the effect on the stability and overall performance of the AgNW films was investigated. Morphological and elemental analysis of the exposed films was done using SEM and EDX, respectively. Hydroxyethyl cellulose (HEC) was introduced as a polymeric binder and protective agent in order to prevent the exposure of the AgNW surface to corrosive agents in air. A TCE with a sheet resistance of 47.50 Ω/sq and transmittance of 89.70% at 550 nm without any harsh post-treatments, was demonstrated. These electrodes were used to fabricate a transparent flexible touch screen.

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Risperidone/Randomly Methylated β-Cyclodextrin Inclusion Complex—Compatibility Study with Pharmaceutical Excipients

Molecules ◽

10.3390/molecules26061690 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1690

Author(s):

Laura Sbârcea ◽

Ionuț-Mihai Tănase ◽

Adriana Ledeți ◽

Denisa Cîrcioban ◽

Gabriela Vlase ◽

...

Keyword(s):

Inclusion Complex ◽

Uv Spectroscopy ◽

Magnesium Stearate ◽

Phase Solubility ◽

Compatibility Study ◽

Spectroscopic Techniques ◽

Ambient Conditions ◽

Pharmaceutical Excipients ◽

Supramolecular Adduct ◽

Anhydrous Lactose

Risperidone (RSP) is an atypical antipsychotic drug used in treating schizophrenia, behavioral, and psychological symptoms of dementia and irritability associated with autism. The drug substance is practically insoluble in water and exhibits high lipophilicity. It also presents incompatibilities with pharmaceutical excipients such as magnesium stearate, lactose, and cellulose microcrystalline. RSP encapsulation by randomly methylated β-cyclodextrin (RM-β-CD) was performed in order to enhance drug solubility and stability and improve its biopharmaceutical profile. The inclusion complex formation was evaluated using thermal methods, powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy, and saturation solubility studies. The 1:1 stoichiometry ratio and the apparent stability constant of the inclusion complex were determined by means of the phase solubility method. The compatibility between the supramolecular adduct and pharmaceutical excipients starch, anhydrous lactose, magnesium stearate, and cellulose microcrystalline was studied employing thermoanalytical tools (TG-thermogravimetry/DTG-derivative thermogravimetry/HF-heat flow) and spectroscopic techniques (UATR-FTIR, PXRD). The compatibility study reveals that there are no interactions between the supramolecular adduct with starch, magnesium stearate, and cellulose microcrystalline, while incompatibility with anhydrous lactose is observed even under ambient conditions. The supramolecular adduct of RSP with RM-β-CD represents a valuable candidate for further research in developing new formulations with enhanced bioavailability and stability, and the results of this study allow a pertinent selection of three excipients that can be incorporated in solid dosage forms.

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Fractionation of polymethylene chains: An electron crystallographic investigation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100145315 ◽

1986 ◽

Vol 44 ◽

pp. 794-795

Author(s):

Douglas L. Dorset

Keyword(s):

Cross Section ◽

Binary Systems ◽

Linear Chain ◽

Pure Component ◽

Organic Substrates ◽

Crystallographic Investigation ◽

X Ray Diffraction ◽

X Ray ◽

Molecular Sizes ◽

The Stability

A variety of linear chain materials exist as polydisperse systems which are difficultly purified. The stability of continuous binary solid solutions assume that the Gibbs free energy of the solution is lower than that of either crystal component, a condition which includes such factors as relative molecular sizes and shapes and perhaps the symmetry of the pure component crystal structures.Although extensive studies of n-alkane miscibility have been carried out via powder X-ray diffraction of bulk samples we have begun to examine binary systems as single crystals, taking advantage of the well-known enhanced scattering cross section of matter for electrons and also the favorable projection of a paraffin crystal structure posited by epitaxial crystallization of such samples on organic substrates such as benzoic acid.

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Structure, Stability and Water Adsorption on Ultra-Thin TiO2 Supported on TiN

10.26434/chemrxiv.8425367.v1 ◽

2019 ◽

Author(s):

Jose Julio Gutierrez Moreno ◽

Marco Fronzi ◽

Pierre Lovera ◽

alan O'Riordan ◽

Mike J Ford ◽

...

Keyword(s):

Density Functional ◽

Water Adsorption ◽

Chemical Potential ◽

Energy Gap ◽

Molecular Water ◽

Structure Stability ◽

Ambient Conditions ◽

Rutile Structure ◽

The Stability ◽

The One

Interfacial metal-oxide systems with ultrathin oxide layers are of high interest for their use in catalysis. In this study, we present a density functional theory (DFT) investigation of the structure of ultrathin rutile layers (one and two TiO2 layers) supported on TiN and the stability of water on these interfacial structures. The rutile layers are stabilized on the TiN surface through the formation of interfacial Ti–O bonds. Charge transfer from the TiN substrate leads to the formation of reduced Ti3+ cations in TiO2. The structure of the one-layer oxide slab is strongly distorted at the interface, while the thicker TiO2 layer preserves the rutile structure. The energy cost for the formation of a single O vacancy in the one-layer oxide slab is only 0.5 eV with respect to the ideal interface. For the two-layer oxide slab, the introduction of several vacancies in an already non-stoichiometric system becomes progressively more favourable, which indicates the stability of the highly non-stoichiometric interfaces. Isolated water molecules dissociate when adsorbed at the TiO2 layers. At higher coverages the preference is for molecular water adsorption. Our ab initio thermodynamics calculations show the fully water covered stoichiometric models as the most stable structure at typical ambient conditions. Interfacial models with multiple vacancies are most stable at low (reducing) oxygen chemical potential values. A water monolayer adsorbs dissociatively on the highly distorted 2-layer TiO1.75-TiN interface, where the Ti3+ states lying above the top of the valence band contribute to a significant reduction of the energy gap compared to the stoichiometric TiO2-TiN model. Our results provide a guide for the design of novel interfacial systems containing ultrathin TiO2 with potential application as photocatalytic water splitting devices.

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The art and science of drug titration

Therapeutic Advances in Drug Safety ◽

10.1177/2042098620958910 ◽

2020 ◽

Vol 11 ◽

pp. 204209862095891

Author(s):

Aisling R. Caffrey ◽

Eric P. Borrelli

Keyword(s):

Real World ◽

Therapeutic Index ◽

Clinical Expertise ◽

Coordination Of Care ◽

Patient Centered ◽

Narrow Therapeutic Index ◽

Drug Dosing ◽

Scientific Principles ◽

Suboptimal Adherence ◽

Personalized Approach

A “one-size-fits-all” approach has been the standard for drug dosing, in particular for agents with a wide therapeutic index. The scientific principles of drug titration, most commonly used for medications with a narrow therapeutic index, are to give the patient adequate and effective treatment, at the lowest dose possible, with the aim of minimizing unnecessary medication use and side effects. The art of drug titration involves the interplay of scientific drug titration principles with the clinical expertise of the healthcare provider, and an individualized, patient-centered partnership between the provider and the patient to review the delicate balance of perceived benefits and risks from both perspectives. Drug titration may occur as up-, down-, or cross-titration depending on whether the goal is to reach or maintain a therapeutic outcome, decrease the risk of adverse effects, or prevent withdrawal/discontinuation syndromes or recurrence of disease. Drug titration introduces additional complexities surrounding the conduct of clinical trials and real-world studies, confounding our understanding of the true effect of medications. In clinical practice, wide variations in titration schedules may exist due to a lack of evidence and consensus on titration approaches that achieve an optimal benefit-harm profile. Further, drug titration may be challenging for patients to follow, resulting in suboptimal adherence and may require increased healthcare-related visits and coordination of care amongst providers. Despite the challenges associated with drug titration, it is a personalized approach to drug dosing that blends science with art, and with supportive real-world outcomes-based evidence, can be effective for optimizing pharmacotherapeutic outcomes and improving drug safety.

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Tetrabutylammonium cations for moisture-resistant and semitransparent perovskite solar cells

Journal of Materials Chemistry A ◽

10.1039/c7ta06735f ◽

2017 ◽

Vol 5 (42) ◽

pp. 22325-22333 ◽

Cited By ~ 25

Author(s):

Isabella Poli ◽

Salvador Eslava ◽

Petra Cameron

Keyword(s):

Thin Films ◽

Solar Cells ◽

Perovskite Solar Cells ◽

Ambient Conditions ◽

The Stability ◽

Moisture Resistant

Tetra-butylammonium cations have been partially substituted for methylammonium cations in perovskite thin films. The stability of devices stored under ambient conditions was enhanced by the presence of TBA and cells with high mol% TBA were found to have reasonable efficiencies while being semi-transparent.

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Studies on Polyaniline: Polyethyleneterephthalate Films

Solid State Phenomena ◽

10.4028/www.scientific.net/ssp.111.99 ◽

2006 ◽

Vol 111 ◽

pp. 99-102 ◽

Cited By ~ 2

Author(s):

A.A. Ahmed ◽

Faiz Mohammad

Keyword(s):

Electrical Conductivity ◽

Electrical Properties ◽

Arrhenius Equation ◽

Great Increase ◽

Thermooxidative Stability ◽

Ambient Conditions ◽

Dc Electrical Conductivity ◽

The Stability ◽

Almost All ◽

Conductivity Retention

The films of polyaniline:polyethyleneterephthalate films were prepared by polymerizing aniline soaked in polyethyleneterephthalate films of different thicknesses. The films were characterized by FTIR as well as for their electrical properties. The electrical properties of the films were observed to be of good quality as almost all the films showed a great increase in their electrical conductivity from insulator to semiconductor region after doping with hydrochloric acid. All the films in their doped state follow the Arrhenius equation for the temperature dependence of electrical conductivity from 35 to 115oC. The thermooxidative stability was studied by thermogravimetry and differential thermal analysis. The stability in terms of dc electrical conductivity retention was also studied under ambient conditions by two slightly different techniques viz. isothermal and cyclic techniques. The dc electrical conductivity of the films was found to be stable below 90oC for all the films under ambient conditions.

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Systematic treatment and prevention of cardiac digoxin toxicity

International Journal of Community Medicine and Public Health ◽

10.18203/2394-6040.ijcmph20212830 ◽

2021 ◽

Author(s):

Omar Rezk Alshaer ◽

Abdullah Obaid Binobaid ◽

Abdelelah Hesham Mofti ◽

Mohannad Mahmood Sadagah ◽

Khalid Mustafa Olwi ◽

...

Keyword(s):

Therapeutic Index ◽

Digoxin Toxicity ◽

Clinical Settings ◽

Clinical Effects ◽

Systematic Treatment ◽

Narrow Therapeutic Index ◽

Serious Adverse Events ◽

Treatment And Prevention ◽

Cost Efficacy ◽

The Cost

Digoxin has a narrow therapeutic index, such as complicated pharmacokinetics and dynamics. Many drug interactions may occur when the administration of one drug alters the clinical effects of another. As a result, digoxin toxicity can be a common condition within clinical settings that might lead to the development of many morbidities and even mortality. Many studies were published to investigate the efficacy and safety of different management modalities to enhance the outcomes that follow digoxin administration. The aim of the study was to discuss the approaches to systematically treat and prevent the development of cardiac digoxin toxicity. The findings are based on evidence from previous studies in the literature. To be specific, Fab fragments are the most effective modalities that can be used to treat severe cases within ideal periods. However, evidence regarding their administration for asymptomatic or mild cases is still poor regarding the cost-efficacy and the development of serious adverse events. Physicians should primarily care for a better intervention as it is usually associated with a significantly more enhanced prognosis and clinical outcomes. Nevertheless, adequate monitoring of the patients and evaluation of their personal and medical history are important steps in the process, and further approaches are still needed. Also, detailed information about our intended outcomes is furtherly discussed within the manuscript.

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