Host-Guest Interaction Study of Olmesartan Medoxomil with ß-Cyclodextrin Derivatives.

Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated ß-cyclodextrin (RM-ß-CD) and heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin (TM-ß-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG-thermogravimetry; DTG-derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host-guest system OLM/RM-ß-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-ß-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.

Pharmaceutical Applications of Biomass Polymers: Review of Current Research and Perspectives.

Polymers derived from natural biomass have emerged as a valuable resource in the field of biomedicine due to their versatility. Polysaccharides, peptides, proteins, and lignin have demonstrated promising results in various applications, including drug delivery design. However, several challenges need to be addressed to realize the full potential of these polymers. The current paper provides a comprehensive overview of the latest research and perspectives in this area, with a particular focus on developing effective methods and efficient drug delivery systems. This review aims to offer insights into the opportunities and challenges associated with the use of natural polymers in biomedicine and to provide a roadmap for future research in this field.

Host-Guest Complexation of Itraconazole with Cyclodextrins for Bioavailability Enhancement.

Itraconazole is an antifungal agent included in the triazole pharmacological classification that belongs to the BCS class II, characterized by a low solubility in an aqueous medium (of 1 ng/mL, at neutral pH), which is frequently translated in a low oral bioavailability but with a high permeability. In this sense, it is necessary to find solutions to increase/improve the solubility of itraconazole in the aqueous environment. The main purpose of this study is the preparation and analysis of five different guest-host inclusion complexes containing intraconazole. Initially, a blind docking process was carried out to determine the interactions between itraconazole and the selected cyclodextrins. The second step of the study was to find out if the active pharmaceutical ingredient was entrapped in the cavity of the cyclodextrin, by using spectroscopic and thermal techniques. Also, the antifungal activity of the inclusion complexes was studied to examine if the entrapment of itraconazole influences the therapeutic effect. The results showed that the active substance was entrapped in the cavity of the cyclodextrins, with a molar ratio of 1:3 (itraconazole-cyclodextrin), and that the therapeutic effect was not influenced by the entrapment.

Romanian Wild-Growing Chelidonium majus-An Emerging Approach to a Potential Antimicrobial Engineering Carrier System Based on AuNPs: In Vitro Investigation and Evaluation.

Novel nanotechnology based on herbal products aspires to be a high-performing therapeutic platform. This study reports the development of an original engineering carrier system that jointly combines the pharmacological action of Chelidonium majus and AuNPs, with unique properties that ensure that the limitations imposed by low stability, toxicity, absorption, and targeted and prolonged release can be overcome. The metabolite profile of Romanian wild-grown Chelidonium majus contains a total of seventy-four phytochemicals belonging to eight secondary metabolite categories, including alkaloids, amino acids, phenolic acids, flavonoids, carotenoids, fatty acids, sterols, and miscellaneous others. In this study, various techniques (XRD, FTIR, SEM, DLS, and TG/DTG) were employed to investigate his new carrier system's morpho-structural and thermal properties. In vitro assays were conducted to evaluate the antioxidant potential and release profile. The results indicate 99.9% and 94.4% dissolution at different pH values for the CG-AuNPs carrier system and 93.5% and 85.26% for greater celandine at pH 4 and pH 7, respectively. Additionally, three in vitro antioxidant assays indicated an increase in antioxidant potential (flavonoid content 3.8%; FRAP assay 24.6%; and DPPH 24.4%) of the CG-AuNPs carrier system compared to the herb sample. The collective results reflect the system's promising perspective as a new efficient antimicrobial and anti-inflammatory candidate with versatile applications, ranging from target delivery systems, oral inflammation (periodontitis), and anti-age cosmetics to extending the shelf lives of products in the food industry.

An Innovative Approach to a Potential Neuroprotective Sideritis scardica-Clinoptilolite Phyto-Nanocarrier: In Vitro Investigation and Evaluation.

The cutting-edge field of nanomedicine combines the power of medicinal plants with nanotechnology to create advanced scaffolds that boast improved bioavailability, biodistribution, and controlled release. In an innovative approach to performant herb nanoproducts, Sideritis scardica Griseb and clinoptilolite were used to benefit from the combined action of both components and enhance the phytochemical's bioavailability, controlled intake, and targeted release. A range of analytical methods, such as SEM-EDX, FT-IR, DLS, and XDR, was employed to examine the morpho-structural features of the nanoproducts. Additionally, thermal stability, antioxidant screening, and in vitro release were investigated. Chemical screening of Sideritis scardica Griseb revealed that it contains a total of ninety-one phytoconstituents from ten chemical categories, including terpenoids, flavonoids, amino acids, phenylethanoid glycosides, phenolic acids, fatty acids, iridoids, sterols, nucleosides, and miscellaneous. The study findings suggest the potential applications as a promising aspirant in neurodegenerative strategy.

Synthesis and Characterization of Polymer-Based Membranes for Methotrexate Drug Delivery.

Methotrexate or amethopterin or 4-amino-N10-methyl pteroylglutamic acid is used for treating autoimmune diseases, as well as certain malignancies. Drug delivery systems, which are based on biopolymers, can be developed to improve the therapeutic and pharmacological properties of topically administered drugs. Biopolymers improve the therapeutic effect of drugs, mainly by improving their biodistribution and modulating drug release. This study presents the synthesis of membranes based on anionic polysaccharides and cationic polysaccharides for transdermal delivery of the active ingredient methotrexate, as well as a compatibility study between methotrexate and each of the components used in the prepared membranes. The obtained membranes based on different marine polysaccharides, namely κ-carrageenan and chitosan, for the release of the active ingredient methotrexate were characterized using techniques such as TG, FTIR, UV-Vis spectrophotometry, FTIR microscopy, water absorption capacity, water vapor permeability, and biodegradation rate. Following the studies, the membranes suitable for the transdermal release of the active substance were validated.

The Influence of an Isocyanate Structure on a Polyurethane Delivery System for 2'-Deoxycytidine-5'-monophosphate.

The delivery of nucleosides represents an interesting research trend in recent years due to their application in various viral infections. The main aims of this study were to develop and to characterize polyurethane particles that are intended to be used for the transport of nucleosides. Three samples have been prepared using aliphatic diisocyanates, a mixture of polyethylene glycol, polycaprolactone, and diols, respectively. The samples were characterized through refractivity measurements, drug loading efficacy, release and penetration rate investigations, FTIR and Raman spectroscopy, thermal analyses, Zetasizer, SEM, HDFa cells viability, and irritation tests on mice skin. The results indicate the obtaining of particles with sizes between 132 and 190 nm, positive Zeta potential values (28.3-31.5 mV), and a refractivity index around 1.60. A good thermal stability was found, and SEM images show a medium tendency to agglomerate. The samples' color, pH, and electrical conductivity have changed only to a small extent over time, and the evaluations indicate an almost 70% encapsulation efficacy, a prolonged release, and that around 70% of particles have penetrated an artificial membrane in the first 24 h. The synthesized products should be tested in further clinical trials, and the current tests on cell cultures and mice skin revealed no side effects.

Wild-Grown Romanian Helleborus purpurascens Approach to Novel Chitosan Phyto-Nanocarriers-Metabolite Profile and Antioxidant Properties.

The current nanomedicinal approach combines medicinal plants and nanotechnology to create new scaffolds with enhanced bioavailability, biodistribution and controlled release. In an innovative approach to herb encapsulation in nanosized chitosan matrices, wild-grown Romanian Helleborus purpurascens was used to prepare two new chitosan nanocarriers. The first carrier preparation involved the nanoencapsulation of hellebore in chitosan. The second carrier emerged from two distinct stages: hellebore-AgNPs phyto-carrier system succeeded by nanoencapsulation in chitosan. The morphostructural characteristics and thermal behavior of these newly prepared nanocarriers were examined using FT-IR, XRD, DLS, SEM, EDS and thermogravimetric analyses. In addition, the encapsulation yield, encapsulation efficiency and encapsulation contents were investigated. The antioxidant activity was estimated using four in vitro, noncompetitive methods: total phenolic assay; 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay; phosphomolybdate (i.e., total antioxidant capacity); and iron(III)-phenanthroline antioxidant assay. Moreover, this study reports the first low-molecular-weight metabolite profile of wild-grown Romanian Helleborus purpurascens Waldst. & Kit. A total of one hundred and five secondary metabolites were identified in the mass spectra (MS)-positive mode from fourteen secondary metabolite categories (alkaloids, butenolides, bufadienolides, phytoecdysteroids, amino acids and peptides, terpenoids, fatty acids, flavonoids, phenolic acids, sterols, glycosides, carbohydrates, nucleosides and miscellaneous). The collective results suggest the potential application is a promising new antioxidant vehicle candidate in tumor therapeutic strategy.

Romanian Wild-Growing Armoracia rusticana L.-Untargeted Low-Molecular Metabolomic Approach to a Potential Antitumoral Phyto-Carrier System Based on Kaolinite.

Horseradish is a globally well-known and appreciated medicinal and aromatic plant. The health benefits of this plant have been appreciated in traditional European medicine since ancient times. Various studies have investigated the remarkable phytotherapeutic properties of horseradish and its aromatic profile. However, relatively few studies have been conducted on Romanian horseradish, and they mainly refer to the ethnomedicinal or dietary uses of the plant. This study reports the first complete low-molecular-weight metabolite profile of Romanian wild-grown horseradish. A total of ninety metabolites were identified in mass spectra (MS)-positive mode from nine secondary metabolite categories (glucosilates, fatty acids, isothiocyanates, amino acids, phenolic acids, flavonoids, terpenoids, coumarins, and miscellaneous). In addition, the biological activity of each class of phytoconstituents was discussed. Furthermore, the development of a simple target phyto-carrier system that collectively exploits the bioactive properties of horseradish and kaolinite is reported. An extensive characterization (FT-IR, XRD, DLS, SEM, EDS, and zeta potential) was performed to investigate the morpho-structural properties of this new phyto-carrier system. The antioxidant activity was evaluated using a combination of three in vitro, non-competitive methods (total phenolic assay, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay, and phosphomolybdate (total antioxidant capacity)). The antioxidant assessment indicated the stronger antioxidant properties of the new phyto-carrier system compared with its components (horseradish and kaolinite). The collective results are relevant to the theoretical development of novel antioxidant agent fields with potential applications on antitumoral therapeutic platforms.

Untargeted Metabolomic Approach of Curcuma longa to Neurodegenerative Phytocarrier System Based on Silver Nanoparticles.

Curcuma is one of the most famous medicinal and tropical aromatic plants. Its health benefits have been appreciated and exploited in traditional Asian medicine since ancient times. Various studies have investigated its complex chemical composition and demonstrated the remarkable therapeutic properties of curcuma's phytoconstituents. Oxidative stress is a decisive driving factor triggering numerous pathologies (neurodegenerative, psychiatric and cardiovascular diseases; diabetes; tumors, etc.). Numerous recent studies have focused on the use of natural compounds and nanomaterials as innovative molecular targeting agents as effective therapeutic strategies. In this study, we report, for the first time, the development of a simple target phytocarrier system that capitalizes on the bioactive properties of curcuma and AgNPs. The complete metabolic profile of curcuma was determined based on gas chromatography-mass spectrometry (GC-MS) and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS). A total of 80 metabolites were identified under mass spectra (MS)-positive mode from 10 secondary metabolite categories: terpenoids, amino acids, diarylheptanoids, flavonoids, phenolic acids, steroids, fatty acids, coumarins, alkaloids and miscellaneous. In addition, the biological activity of each class of metabolites was discussed. A comprehensive characterization (FT-IR, UV-Vis, DLS, SEM, TEM, EDS, zeta potential and XRD) was performed to study the morphostructural properties of this new phytocarrier system. Antioxidant activity of the new phytocarrier system was evaluated using a combination of in vitro methods (total phenolic assay, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and cyclic voltammetric method (Trolox equivalent antioxidant capacity (TEAC) electrochemical assay)). Antioxidants assays showed that the phytocarrier system exhibits superior antioxidant properties to those of its components, i.e., curcuma or citrate-coated-AgNPs. These data confirm the potential to enhance relevant theoretical knowledge in the area of innovative antioxidant agents, with potential application in neurodegenerative therapeutic strategies.

Preliminary Study of κ-Carrageenan Based Membranes for Anti-Inflammatory Drug Delivery.

This study proposes a simple and effective method to obtain ultra-thin membranes based on κ-carrageenan. Two types of membranes were obtained, one based on κ-carrageenan and the second type based on κ-carrageenan, hydroxyethyl cellulose and the plasticizer (glycerol). Three non-steroidal anti-inflammatory drugs (Dexketoprofen trometamol, Meloxicam, Diclofenac sodium) and a glucocorticoid (Dexamethasone) were introduced, looking for the best option for incorporation. The obtained membranes were characterized by FTIR, TG/DTG and UV-VIS methods and the data collected following these methods indicated success in terms of the incorporation of the active substance, as well as the high thermal stability in the temperature range 37-100 °C of both the matrices of membrane types, as well as the membranes with the drug incorporated. All the studies carried out led to the conclusion that within all the membranes the anti-inflammatory substances were intact and, thus we can say that these membranes can be used for transdermal administration of the studied anti-inflammatory substances.

Highly efficient engineered waste eggshell-fly ash for cadmium removal from aqueous solution.

Sustainable waste and water management are key components of the newest EU policy regarding the circular economy. Simple, performant and inexpensive water treatment methods based on reusing waste are prerequisites for human health, sustainable development and environmental remediation. The design of performant, cost-effective absorbents represents a topical issue in wastewater treatment. This study aimed to investigate the development of a newly engineered adsorbent by functionalizing two different types of waste (industrial and food) with magnetic nanoparticles as environmentally friendly, highly efficient, cheap material for cadmium removal from aqueous solutions. This nano-engineered adsorbent (EFM) derived from waste eggshell and fly ash was used to remove the cadmium from the aqueous solution. SEM analysis has demonstrated that magnetite nanoparticles were successfully loaded with each waste. In addition, was obtained a double functionalization of the eggshell particles with ash and magnetite particles. As a result of this, the EFM surface area substantially increased, as confirmed by BET. A comprehensive characterization (BET, FT-IR, SEM, XRD and TGA) was performed to study the properties of this newly engineered adsorbent. Batch experiments were conducted to investigate the influence of different reaction parameters: temperature, pH, contact time, dosage adsorbent, initial concentration. Results showed that cadmium adsorption reached equilibrium in 120 min., at pH 6.5, for 0.25 g of adsorbent. The maximum efficiency was 99.9%. The adsorption isotherms research displayed that the Cd2+ adsorption fitted on the Freundlich model indicated a multi-molecular layer adsorption process. In addition, the thermodynamic study (ΔG < 0, ΔH > 0; ΔS > 0) shows that cadmium adsorption is a spontaneous and endothermic process. The adsorbent kinetic study was described with the pseudo-second-order model indicating a chemisorption mechanism. Desorption results showed that the nano-engineered adsorbent (EFM) can be reused. These data confirmed the possibility to enrich relevant theoretical knowledge in the field of waste recovery for obtaining newly designed adsorbents, performant and inexpensive for wastewater remediation.

Preliminary Study for the Preparation of Transmucosal or Transdermal Patches with Acyclovir and Lidocaine.

The present study aimed to prepare and evaluate patches for the controlled release of lidocaine/acyclovir and the binary mixture between lidocaine: acyclovir in the oral cavity. Mucoside adhesive patches containing 12.5 mg/cm2 lidocaine/acyclovir or binary mixture base were developed by a solvent casting method using sodium alginate, polyvinylpyrrolidone (PVP), glycerol (Gly), polyvinyl alcohol (PVA), and Span 80 (S). Binary mixtures between all components were prepared before the patches' formulation in order to be able to check the substance compatibility. All formulated patches were analyzed by FT-IR spectroscopy, UV-Vis analysis, thermogravimetry (TGA), and scanning electron microscopy (SEM). FT-IR and TGA analyses were also used to check compatibility between binary mixtures. The study establishes which membranes are indicated in the controlled release of lidocaine/acyclovir and those membranes that contain both active principles. Membranes based on alginate, PVP, and PVA can be used to release the active substance. Simultaneously, membranes with SPAN used as a gelling agent were excluded due to the interaction with the active substance. The following membranes composition have been chosen for lidocaine release: Alginate:Gly and Alginate:Gly:PVP. At the same time, the following membrane compositions were chosen for acyclovir membranes: Alginate:Gly:PVP and Alginate:PVA:Gly. Both active substances could be included to obtain a homogeneous distribution only in the membrane based on alginate, PVA, and Gly.

Risperidone/Randomly Methylated ß-Cyclodextrin Inclusion Complex-Compatibility Study with Pharmaceutical Excipients.

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 ß-cyclodextrin (RM-ß-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-ß-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.

Precious metals recovery from aqueous solutions using a new adsorbent material.

Platinum group metals (PGMs) palladium, platinum, and ruthenium represent the key materials for automotive exhaust gas treatment. Since there are no adequate alternatives, the importance of these metals for the automotive industry is steadily rising. The high value of PGMs in spent catalysts justifies their recycling. Therefore, it is really important to recovery platinum group metals from aqueous solutions. Of the many PGMs recovery procedures, adsorption is a process with a good efficiency, but an important role is played by the adsorbent material used into the process. In order to improve the adsorption properties of materials were developed new methods for chemical modification of the solid supports, through functionalization with different extractants. In present paper a new adsorbent material (Chitosan-DB18C6) was used for PGMs recovery. The new adsorbent material was produced by impregnating Chitosan with dibenzo-18-crown-6-ether using Solvent Impregnated Resin (SIR) method. The crown ethers were chosen as extractant due to their known ability to bind metallic ions, whether they are symmetrically or unsymmetrically substituted. In order to determine the PGMs recovery efficiency for new prepared adsorbent material the equilibrium and kinetic studies were performed. Also, to study the PGMs adsorption mechanism the experimental data were modelled using pseudo-first-order and pseudo-second order kinetic models. Experimental data were fitted with three equilibrium isotherm models: Langmuir, Freundlich and Sips. The results proved that new adsorbent material (Chitosan-DB18C6) is an efficient adsorbent for PGMs recovery from aqueous solutions.

Formulation and Characterization of Alginate-Based Membranes for the Potential Transdermal Delivery of Methotrexate.

The aim of this study is to obtain and characterize of alginate-based membranes, as well as to choose the most suitable membrane type for the transdermal release of methotrexate. The paper presents the synthesis of four types of membranes based on alginate to which are added other copolymers (Carbopol, Tween, and Polyvinylpyrrolidone) as well as other components with different roles. Membranes and binary mixtures made between the components used in membrane synthesis and methotrexate are analyzed by thermogravimetric techniques, FTIR and UV spectroscopic techniques as well as SEM. The analyses aim to establish the type of membrane most indicated in the use of the controlled release of methotrexate, namely those membranes in which there are no interactions that could inactivate the active substance. Following these studies, it was concluded that membranes obtained from alginate/alginate and Tw can be used for methotrexate release. The membrane obtained from alginate and carbopol was excluded from the beginning because it is not homogeneous. Regarding the AGP-MTX membrane, it presents interactions with the active substance, carboxylate group interactions argued by TGA and FTIR studies, and interactions that occur in aqueous medium.

Encapsulation of Risperidone by Methylated ß-Cyclodextrins: Physicochemical and Molecular Modeling Studies.

Risperidone (RSP) is an atypical antipsychotic drug which acts as a potent antagonist of serotonin-2 (5TH2) and dopamine-2 (D2) receptors in the brain; it is used to treat schizophrenia, behavioral and psychological symptoms of dementia and irritability associated with autism. It is a poorly water soluble benzoxazole derivative with high lipophilicity. Supramolecular adducts between drug substance and two methylated ß-cyclodextrins, namely heptakis(2,6-di-O-methyl)-ß-cyclodextrin (DM-ß-CD) and heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin (TM-ß-CD) were obtained in order to enhance RSP solubility and improve its biopharmaceutical profile. The inclusion complexes were evaluated by means of thermoanalytical methods (TG-thermogravimetry/DTG-derivative thermogravimetry/HF-heat flow), powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy and saturation solubility studies. Job's method was employed for the determination of the stoichiometry of the inclusion complexes, which was found to be 2:1 for both guest-host systems. Molecular modeling studies were carried out for an in-depth characterization of the interaction between drug substance and cyclodextrins (CDs). The physicochemical properties of the supramolecular systems differ from those of RSP, demonstrating the inclusion complex formation between drug and CDs. The RSP solubility was enhanced as a result of drug encapsulation in the CDs cavity, the higher increase being obtained with DM-ß-CD as host; the guest-host system RSP/DM-ß-CD can thus be a starting point for further research in developing new formulations containing RSP, with enhanced bioavailability.

Solid State Stability and Kinetics of Degradation for Candesartan-Pure Compound and Pharmaceutical Formulation.

The aim of this work was to assess the impact of an excipient in a pharmaceutical formulation containing candesartan cilexetil over the decomposition of the active pharmaceutical ingredient and to comparatively investigate the kinetics of degradation during thermolysis in an oxidative atmosphere under controlled thermal stress. To achieve this, the samples were chosen as follows: pure candesartan cilexetil and a commercial tablet of 32 mg strength. As a first investigational tool, Universal attenuated total reflection Fourier transform infrared (UATR-FTIR) spectroscopy was chosen in order to confirm the purity and identity of the samples, as well as to check if any interactions took place in the tablet between candesartan cilexetil and excipients under ambient conditions. Later on, samples were investigated by thermal analysis, and the elucidation of the decomposition mechanism was achieved solely after performing an in-depth kinetic study, namely the use of the modified non-parametric kinetics (NPK) method, since other kinetic methods (American Society for Testing and Materials-ASTM E698, Friedman and Flynn-Wall-Ozawa) led to inadvertencies. The NPK method suggested that candesartan cilexetil and the tablet were degraded by the contribution of two steps, the main being represented by chemical degradation and the secondary being a physical transformation. The excipients chosen in the formulation seemed to have a stabilizing effect on the decomposition of the candesartan cilexetil that was incorporated into the tablet, relative to pure active pharmaceutical ingredient (API), since the apparent activation energy for the decomposition of the tablet was 192.5 kJ/mol, in comparison to 154.5 kJ/mol for the pure API.

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.

Comparative Solid-State Stability of Perindopril Active Substance vs. Pharmaceutical Formulation.

This paper presents the results obtained after studying the thermal stability and decomposition kinetics of perindopril erbumine as a pure active pharmaceutical ingredient as well as a solid pharmaceutical formulation containing the same active pharmaceutical ingredient (API). Since no data were found in the literature regarding the spectroscopic description, thermal behavior, or decomposition kinetics of perindopril, our goal was the evaluation of the compatibility of this antihypertensive agent with the excipients in the tablet under ambient conditions and to study the effect of thermal treatment on the stability of perindopril erbumine. ATR-FTIR (Attenuated Total Reflectance Fourier Transform Infrared) spectroscopy, thermal analysis (thermogravimetric mass curve (TG-thermogravimetry), derivative thermogravimetric mass curve (DTG), and heat flow (HF)) and model-free kinetics were chosen as investigational tools. Since thermal behavior is a simplistic approach in evaluating the thermal stability of pharmaceuticals, in-depth kinetic studies were carried out by classical kinetic methods (Kissinger and ASTM E698) and later with the isoconversional methods of Friedman, Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa. It was shown that the main thermal degradation step of perindopril erbumine is characterized by activation energy between 59 and 69 kJ/mol (depending on the method used), while for the tablet, the values were around 170 kJ/mol. The used excipients (anhydrous colloidal silica, microcrystalline cellulose, lactose, and magnesium stearate) should be used in newly-developed generic solid pharmaceutical formulations, since they contribute to an increased thermal stability of perindopril erbumine.