Influence Of Excipients Research Articles

Solid Self-Microemulsifying Drug Delivery System for Improved Oral Bioavailability of Relugolix: Preparation and Evaluation.

To improve the oral absorption of relugolix (RLGL), which has low oral bioavailability due to its low solubility and being a substrate of P-glycoprotein (P-gp). A solid self-microemulsifying drug delivery system of relugolix (RLGL-S-SMEDDS) was prepared and evaluated in vitro and in vivo. The composition of the solid self-microemulsifying drug delivery system (S-SMEDDS) was selected by solubility study and pseudo-ternary phase diagram, and further optimized by Design-Expert optimization design. The optimized RLGL-S-SMEDDS were evaluated in terms of particle size, zeta potential, morphology analysis, thermodynamic stability, drug release, flow properties, transporter pathways in Caco-2 cells, the influence of excipients on the intestinal transporters, transport within Caco-2 cell monolayers and transport in lymphocyte. In vivo pharmacokinetic study and toxicological study were also conducted. The optimum formulation for self-microemulsifying drug delivery system (SMEDDS) consists of Ethyl Oleate (26% of the weight), Solutol HS15 (49% of the weight), Transcutol HP (25% of the weight) and loaded relugolix (4.8 mg/g). The S-SMEDDS was then formed by adsorbing 2.4 g of SMEDDS onto 1 g of hydrophilic-200 silica. In phosphate buffered saline (PBS) (pH 6.8) release medium containing 1% tween 80, the vitro release studies showed 86% cumulative drug release for RLGL-S-SMEDDS and 3.6% cumulative drug release for RLGL suspensions. In vitro cellular uptake experiments revealed that the uptake of RLGL-S-SMEDDS by Caco-2 cells was three times higher than that of free RLGL, and that S-SMEDDS can enhance the drug absorption through lymphatic absorption and inhibition of intestinal transporter. In vivo pharmacokinetic evaluation demonstrated that the oral bioavailability of RLGL-S-SMEDDS was 1.9 times higher than that of RLGL-suspensions. There was no apparent cardiac, hepatic, splenic, pulmonary or renal toxicity on the surface discovered by pathological analysis after oral administration. It is evident that S-SMEDDS may be a safe and effective method to improve oral absorption of drugs with low oral bioavailability.

Influence of excipients on solubility of oxcarbazepine: Modeling and prediction based on thermodynamic models

In this work, the solubility of oxcarbazepine in polymers (PEG 6000, PEG 20,000, PVP K25, and PVP K30) and their aqueous solutions was investigated by experimental measurement and thermodynamic modeling. Firstly, the solubility of oxcarbazepine in water and polymers was modeled and the corresponding binary interaction parameters (oxcarbazepine + water and oxcarbazepine + polymer) were determined based on the experimental phase equilibrium data. Furthermore, the solubility of oxcarbazepine in the polymer aqueous solution (the mass ratios of polymers in water were 2 %, 4 %, and 6 %) was predicted by the solid-liquid equilibrium (SLE) coupled with the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). It was observed that the predicted results agreed well with the experimental data, and the average relative deviation (ARD) was <7 %. In this study, the solubility of oxcarbazepine in polymer aqueous solution was successfully predicted through the SLE coupled with the PC-SAFT, which was expected to provide theoretical guidance for the selection of pharmaceutical excipients and the rational design of preparations.

A Review on Solid Lipid Nanoparticles as Nano Drug Delivery Transporters

Abstract: Solid lipid nanoparticles (SLN) have several potential uses in research for medicine such as drug discovery and drug delivery, an area at the forefront of evolving area of nanobiotechnology. In general, SLNs were created to address the drawbacks of conventional colloidal carriers, including emulsions, liposomes, and polymeric nanoparticles since they provide various advantages such as favourable release profiles and tailored drug delivery with outstanding physical-chemical stability. Solid lipid nanoparticles are spherical solid lipid particles that are distributed in water or an aqueous surfactant solution and are in the nanometer size range. Therefore, SLN is used to deliver hydrophilic and lipophilic drugs. The review article focuses on various aspects of SLN including the structure, the influence of excipients, the drug incorporation model, the principle of release, the method of preparation, characterization, the route of administration and biodistribution, and the application of SLN.

Development of an ELISA-based device to quantify antibody adsorption directly on medical plastic surfaces

Monoclonal antibodies (mAbs) encounter numerous interfaces during manufacturing, storage, and administration. While protein adsorption at the solid/liquid interface has been widely explored on model surfaces, a key challenge remains – the detection of very small amounts of adsorbed mAb directly on real medical surfaces. This study introduces a novel ELISA-based device, ELIBAG, a new tool for measuring mAb adsorption on medical bags. The efficacy of this device was highlighted by successfully confirming the adsorption of an IgG1 on two medical bag types: a polypropylene IV administration bag and a low-density polyethylene pharmaceutical manufacturing bag. We also investigated IgG1 adsorption on plastic model surfaces, revealing a similar range of mAb bulk concentration for surface saturation on both model and bag surfaces. This innovative device, characterized by its high-throughput and rapid approach, paves the way for extensive investigations into therapeutic proteins, such as mAbs, adsorption on a variety of medical or pharmaceutical surfaces, diverse adsorption conditions, and the influence of excipients employed in mAb formulation, which could enhance the knowledge of mAb interactions with plastic surfaces throughout their lifecycle.

Development of the optimal composition of tablets with the active substance potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate. Message 1. Study of the effect of auxiliary substances on bulk density, bulk density after shrinkage, fluidity and angle of natural slope of powder masses

The pharmaceutical industry continually evolves to meet the demands of modern society for high-quality medications. One avenue of this advancement involves exploring new technologies for manufacturing tablet formulations that adhere to contemporary quality standards. An integral aspect of this process is the careful selection of optimal excipients that preserve the pharmacological activity of the active substance to the greatest extent possible. Investigating the impact of various excipients on the tablet compression process is pivotal to addressing this challenge. Therefore, the study of the influence of excipients on the pharmaco-technological properties of tablets with potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate is an important aspect, so as this substance has pronounced hepatoprotective and antioxidant properties. The aim of the work was to study the effect of excipients on the pharmaco-technological parameters of tablets with the active ingredient potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate obtained by the method direct pressing. Materials and methods. Active substance – potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate, auxiliary substances (excipients based on microcrystalline cellulose, auxiliary substances based on granulated sugars, lubricants, lubricants). The powder mixtures were checked for bulk density, bulk density after compaction, flowability and angle of natural slope. The tablets were pressed by the direct pressing method. The effect of auxiliary substances on the pressing process was studied. Results. The conducted studies show that the powder mass of potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio)acetate and auxiliary substances was characterized by good pharmaco-technological indicators – bulk density and bulk density after compaction, fluidity and angle of natural slope. Further, during the tableting process, it was confirmed that the powder mass has satisfactory properties. In almost all series of experiments, the process of pressing the tablets took place without difficulties, the matrix was evenly filled, but the force of pushing the tablets out of the matrix was different. Conclusions. The study involving 16 excipients, including fillers, disintegrants, and lubricants to develop the composition and technology was conducted of a new tablet medicine containing potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazole-3-yl)thio)acetate. This comprehensive examination enabled us to identify the optimal auxiliary substances that fulfill all the pharmaco-technological requirements stipulated by the State Pharmacopoeia of Ukraine for tablet formulations.

Technological aspects of developing drugs in the form of transmucosal and dispersible films

The creation of new forms of drugs is one of the most important areas of development of the modern pharmaceutical industry. Orodispersible films have a number of advantages over conventional tablets and injections. Developing and scaling technology is time-consuming, resource-intensive, and expensive. The determination of critical parameters affecting the technology and quality of the finished product minimizes the risks of obtaining negative results during implementation and routine industrial production. The work presents the studies of the influence of excipients in the formulation on the characteristics of the dosage form and the technological process. The approach to development was considered from the standpoint of choosing a qualitative composition of the drug. The experiments were aimed at determining the most suitable viscosity of hydroxypropyl methylcellulose (HPMC), which makes up the matrix of the dosage form; optimal polymer- plasticizer ratios have been established. The studies carried out are basic in the creation of a transmucosal dosage form and orodispersible films and make it possible to optimize the process of developing the dosage form and reduce risks during the transfer of technology to production.

Azithromycin-loaded liposomes and niosomes for the treatment of skin infections: Influence of excipients and preparative methods on the functional properties

The aim of this study was to develop azithromycin (AZT)-loaded liposomes (LP) and niosomes (NS) useful for the treatment of bacterial skin infections and acne. LP based on phosphatidylcholine from egg yolk (EPC) or from soybean lecithin (SPC), and NS composed of sorbitan monopalmitate (Span 40) or sorbitan monostearate (Span 60) were prepared through the thin film hydration (TFH) and the ethanol injection (EI) methods. The formulations were subsequently characterized for their physico-chemical and functional properties. Vesicles prepared through TFH showed higher average sizes than the corresponding formulations obtained by EI. All the vesicles presented adequate encapsulation efficiency and a negative ζ potential, which assured good stability during the storage period (except for LP-SPC). Formulations prepared with TFH showed a more prolonged AZT release than those prepared through EI, due to their lower surface area and multilamellar structure, as confirmed by atomic force microscopy nanomechanical characterization. Finally, among all the formulations, NS-Span 40-TFH and LP-EPC-TFH allowed the highest drug accumulation in the skin, retained the antimicrobial activity and did not alter fibroblast metabolism and viability. Overall, they could ensure to minimize the dosing and the administration frequency, thus representing promising candidates for the treatment of bacterial skin infections and acne.

Pharmaceutical-technological Studies on the Development of Optimal Composition of Antibacterial Preparation Sekstafag® (Piobacteriophage Polyvalent) Capsules

Introduction. Nowadays liquid combined therapeutic and prophylactic bacteriophages produced by various manufacturers are widely used. In order to expand the Russian market with highly effective antibacterial phagopreparations it is urgent to develop solid dispersed dosage forms of bacteriophages in the form of solid capsules.Aim. Optimization of biomass composition for encapsulation of antibacterial drug Sekstafag® (Piobacteriophage polyvalent) capsules.Materials and methods. The object of research for the development of encapsulated antibacterial drug is liquid combined polyvalent bacteriophage Sekstafag® (Piobacteriophage polyvalent), which is a mixture of sterile filtrates of six phagolysates of bacteria Staphylococcus spp., Streptococcus spp., Proteus spp., Pseudomonas aeruginosa, Klebsiella pneumoniae, enteropathogenic Escherichia coli. Pharmaceutical-technological tests were carried out according to GF. Granulate was investigated according to the following parameters: description, bulk density, friability. Solid capsules Sekstafag® were tested by the following parameters: mass uniformity, disintegration, acid resistance of bacteriophages in capsules, dissolution. The lytic activity of bacteriophages was evaluated by Appelman’s method. Optimization of Sekstafag® drug formulation in the form of capsules was carried out using generalized Harrington’s desirability function.Results and discussion. In order to optimize the composition of biomass for encapsulation, pharmaceutical compositions consisting of combined bacteriophage Sekstafag® and auxiliary substances were prepared. The influence of excipients on the technological quality parameters of mixtures and capsules of model compositions was studied. According to the empirical system of preferences (desirability) it was revealed that the optimal pharmaceutical-technological characteristics (granulate description, bulk density, bulkiness, capsule mass uniformity, disintegrability, lytic activity, acid resistance of bacteriophage, dissolution) are possessed by the model composition containing combined polyvalent Sekstafag®, methylcellulose, sorbitol, lactose, pectin, sodium alginate, calcium carbonate, magnesium stearate. Originality of the developed composition Sekstafag® (Piobacteriophage polyvalent) in the form of capsules is confirmed by the patent of the Russian Federation № 2660355 "Antibacterial pharmaceutical composition for oral use containing bacteriophages". The drug Sekstafag® (Piobacteriophage polyvalent) capsules, is stable when stored for 18 months at temperatures from 2 to 8 °C.Conclusion. As a result of the conducted complex pharmaceutical-technological research using Harrington’s desirability function the optimal composition of antibacterial preparation Sekstafag® (Piobacteriophage polyvalent) in the form of hard capsules No. 2 was developed.

Investigating the influence of excipients on the stability of biocosmetic nanoemulsions formulated with surfactin as an emulsifier

Investigating the influence of excipients on the stability of biocosmetic nanoemulsions formulated with surfactin as an emulsifier

Influence of Excipients and Pressing Force on the Impurity Content of N-(4-aminobenzoyl)-L-glutamic Acid in Folic Acid Drugs During Storage

Introduction. Excipients, impurities contained in them, and sorbed water are one of the reasons for degradation of the active pharmaceutical substance (API). Excipients effect should be especially evaluated for moisture-sensitive APIs. Folic acid (FA) is an important vitamin for humans. It hydrolyze in water under the action of UV irradiation and main decomposition product is N-(p-aminobenzoyl)glutamic acid (impurity A). We found an increase in the content of impurity A during FA film-coated tablets storage in PVC-film and aluminum foil packaging in the absence of UV irradiation.Aim. Investigate the effect of excipients and parameters of the production process on the content of impurity A during storage of FA drugs.Materials and methods. The FA tablets containing 1.0 mg of API produced by direct compression technology were the objects of study. The pressing force (PF) was varied from 5 to 15 kN.Results and discussion. We found that content of impurity A in tablets containing 93.0 % lactose monohydrate and obtained with PF above 10 kN exceeded limit value during storage for 300 days. Probably lactose simultaneously acts both as a source of free water and as a catalyst for FA hydrolysis. Since the interaction of lactose and FA occurs in the solid phase, pressing accelerates hydrolysis by increasing the contact area of substances and the mobility of water molecules.Conclusion. We found that lactose monohydrate probably is the main cause of FA hydrolysis in drugs. Independently of the mechanism of its action, an increase in the PF above 10 kN leads to an increase in the rate of FA hydrolysis. This is due to an increase in the mobility of water molecules and the contact area between the excipient and API. We have selected the optimum pressure range (5–10 kN) for tablet mix containing lactose monohydrate and FA.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 33.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 33.

Characterizing the specific mechanism of series processed Coptidis Rhizoma by multi-organ metabolomics combined with network pharmacology and molecular docking

BackgroundAfter being processed with different excipients, the clinical application of Coptidis Rhizoma (CR) is differentially investigated. However, the underlying mechanism and material basis are not clear, and there is a lack of attention to the collaborative working mode of herbal medicine during exploration. PurposeTo characterize the specific mechanism of wine/zingiberis rhizoma recens/euodiae fructus processed CR (wCR/zCR/eCR) and to investigate the role of excipients during processing. MethodsThe multi-organ metabolomics approach was employed to explore the target organs of wCR/zCR/eCR and multiple pathways being triggered in each organ. The tissue distribution of CR and wCR/zCR/eCR components was compared to indicate the material basis of efficacy change after processing. Further, the network pharmacology study coupled with experimental validation was conducted to support metabolomic research and predicted active ingredients and core targets, and the molecular docking coupled with binding test was performed to identify the binding between active ingredient and core target. ResultsThe multi-organ metabolomics and network pharmacology study elucidated the intervening effect of wCR on heart/lung, zCR on stomach/colon, and eCR on liver/colon/stomach. Combined with molecular docking, binding test and tissue distribution studies, the specific mechanism was as follows: the wine made iso-quinoline alkaloids in CR more likely to accumulate in heart/lung, thus triggering the core targets of PTGS2, NOS2, ESR1 and SLC6A4 in heart/lung, and thereby highlighting the detoxifying and cardiopulmonary protective effect of wCR. The zingiberis rhizoma recens and euodiae fructus made organic acids in CR more likely to accumulate in stomach/colon and liver/colon/stomach respectively, thus triggering the core targets of ACTB, TNF and PRKCA in stomach/colon, the core targets of ACTB, TNF, PRKCA and GPT in stomach/colon/liver, and thereby highlighting the improving effect of zCR/eCR on digestive function. ConclusionIso-quinoline alkaloids were the material basis of CR for anti-inflammation, and organic acids were mainly responsible for regulating gastrointestinal function. Due to the influence of excipients on the accumulation tendency of CR components, the differentially highlighted application of wCR/zCR/eCR was achieved. These findings propose a novel strategy for processing mechanism research.

An Enhanced Dissolving Cyclosporin-A Inhalable Powder Efficiently Reduces SARS-CoV-2 Infection In Vitro.

This work illustrates the development of a dry inhalation powder of cyclosporine-A for the prevention of rejection after lung transplantation and for the treatment of COVID-19. The influence of excipients on the spray-dried powder's critical quality attributes was explored. The best-performing powder in terms of dissolution time and respirability was obtained starting from a concentration of ethanol of 45% (v/v) in the feedstock solution and 20% (w/w) of mannitol. This powder showed a faster dissolution profile (Weibull dissolution time of 59.5 min) than the poorly soluble raw material (169.0 min). The powder exhibited a fine particle fraction of 66.5% and an MMAD of 2.97 µm. The inhalable powder, when tested on A549 and THP-1, did not show cytotoxic effects up to a concentration of 10 µg/mL. Furthermore, the CsA inhalation powder showed efficiency in reducing IL-6 when tested on A549/THP-1 co-culture. A reduction in the replication of SARS-CoV-2 on Vero E6 cells was observed when the CsA powder was tested adopting the post-infection or simultaneous treatment. This formulation could represent a therapeutic strategy for the prevention of lung rejection, but is also a viable approach for the inhibition of SARS-CoV-2 replication and the COVID-19 pulmonary inflammatory process.

Study of the influence of excipients on the technological parameters of raw materials and the stability of the active substance in the process of manufacturing a solid dosage form

A theoretical study of approaches to solving problems related to the uniformity of the mixture for tableting and the stability of the active substance was carried out. A study of data on the influence of excipients on the properties of the mixture for granulation was carried out. As a result of reference to literary sources, works were found that consider the relationship between the composition, fluidity of the mixture, and mixing time. In addition, work in the field of stability of substances, which is associated with the excipients used, is considered. As a result of the review, various options for influencing the technological characteristics of the mixture, such as dissolution, flowability, segregation, are shown. Observing the relationship between process parameters helps to understand the dependence of quality control parameters on them. Thus, for example, the homogeneity of dosing is highly dependent on segregation and, accordingly, on the fluidity of the mixture. Excipients also have an effect on the stability of the active substance. They should be inert to it, but with the help of excipients it is possible to regulate the required pH level, the percentage of moisture. In some cases, excipients reversibly bind to the active substance to reduce degradation. In conclusion, it was concluded that in the course of developing the technological composition of a solid dosage form, it is necessary to take into account the influence of excipients. When developing the composition, it is possible to select the optimal combination of excipients, which will improve the technological parameters of the mixture, the quality and shelf life of the medicinal product. For the production of generic drugs, this issue is most relevant, since the development of the composition of the drug requires the repetition of the characteristics of the original drug. In this case, it is possible to use an alternative placebo composition, which allows to increase the economic efficiency of production.

Impact of nanocarrier aggregation on EPR-mediated tumor targeting.

The aim of this study was to investigate the influence of excipients on retaining the particle size of methotrexate (MTX) loaded chitosan nanocarriers (CsNP) during lyophilization, which relates to the ability to enlarge the particle size and target specific areas. The nanocarriers were prepared using the ionic gelation technique with tripolyphosphate as a crosslinker. Three lyophilized formulations were used: nanosuspension without Lyoprotectant (NF), with mannitol (NFM), and with sucrose (NFS). The lyophilized powder intended for injection (PI) was examined to assess changes in particle size, product integrity, and comparative biodistribution studies to evaluate targeting ability. After lyophilization, NFS was excluded from in-vivo studies due to the product melt-back phenomenon. The particle size of the NF lyophile significantly increased from 176nm to 261nm. In contrast, NFM restricted the nanocarrier size to 194nm and exhibited excellent cake properties. FTIR, XRD, and SEM analysis revealed the transformation of mannitol into a stable β, δ polymorphic form. Biodistribution studies showed that the nanocarriers significantly increased MTX accumulation in tumor tissue (NF = 2.04 ± 0.27; NFM = 2.73 ± 0.19) compared to the marketed PI (1.45 ± 0.25μg), but this effect was highly dependent on the particle size. Incorporating mannitol yielded positive results in restricting particle size and favoring successful tumor targeting. This study demonstrates the potential of chitosan nanocarriers as promising candidates for targeted tumor drug delivery and cancer treatment.

Analysis of florfenicol in pig plasma using a validated PPT-HPLC-DAD method

High performance liquid chromatography (HPLC) has proven to be an effective tool for examining the disposition kinetics of florfenicol (FF), a synthetic broad-spectrum antibiotic used to treat infectious diseases in veterinary medicine. Modification and optimisation of the protein precipitation (PPT) sample preparation procedure and HPLC with diode array detector (DAD) instrumental method were carried out to ensure conditions suitable for FF analyses in pig plasma samples. Stable supernatants with good plasma mean recoveries of FF (99.8% ± 0.7%RSD) were achieved using 1% v/v phosphoric acid solution in methanol and 10% w/v sodium chloride in aqueous solution. The PPT-HPLCDAD method’s detection limit of 0.004 μg/mL and quantification limit of 0.013 μg/mL provides high sensitivity for analyses of FF in plasma samples. In addition, the optimisation of method conditions resulted in shorter extraction and analysis time and less solvent consumption, which stresses the sustainability of this method in analytical chemistry. The optimised and validated PPT-HPLC-DAD method was applied in a comparative study of FF in pig plasma after administration of veterinary medicinal products. The study was conducted on fattening pigs following repeated intramuscular administration of two similar solutions for injection at a dose of 20 mg FF/kg bodyweight (test groups 1 and 2). The solutions for injection contained the same FF concentration, i.e., 300 mg/mL, but differed in excipients. The aim was to examine the influence of administrated solutions for injection on the extent of exposure to FF in pig plasma. The dynamics of kinetic profiles of FF in pig plasma from both treatments correspond to the FF kinetic profiles published in similar studies. However, differences were observed in the concentrations of FF, which were constant throughout the study, and statistical differences between the test groups were confirmed (P&amp;lt;0.05). Though these findings suggest the possible influence of excipients, a full comprehensive conclusion on the influence of administrated solutions for injection on FF exposure in pig plasma requires additional research.

The influence of excipients on the viscosity of monoclonal antibody solutions

The aggregation propensity of monoclonal antibodies can be modified by adding different cosolutes into the solution. A simple coarse-grained model in the combination with the thermodynamic perturbation theory was used to predict cluster distribution and viscosity of the solutions of IgG4 monoclonal anibody in the presence of L-Arginine Hydrochloride. The data were analysed using binding polynomial to describe the binding of cosolute (Arginine) to the antibody molecule. The results show that by binding to the antibody molecule the cosolute occupies some of the binding sites of the antibody, and in this way reduces the amount of binding sites available to other antibody molecules. The aggregation propensity of the antibody molecules is therefore reduced.

DEVELOPMENT OF SPECTROPHOTOMETRIC METHOD FOR DETERMINATION OF LISINOPRIL IN TABLET DOSAGE FORM

Aim. The research aims at developing a fast, simple, reliable spectrophotometric method according to "green" chemistry principles for the determination of lisinopril in pure substance and in drugs presented on the Ukrainian market.&#x0D; Materials and Methods. Chemical reference standard of lisinopril dihydrate (Sigma-Aldrich, ³98%, HPLC), methanol R (Honeywell Riedel-de Haen™, 99.9%), tablets of Lisinopril-Astrapharm 10 mg), Lisinopril-KRKA 10 mg (Slovenia) and Lisinopril-Teva 10 mg (Germany) were used in this study. Double-beam scanning spectrophotometer "Shimadzu UV-1800" (Japan) connected with software package UV-Probe 2.62 were used for measurements. Absorbance of the solutions in the UV region were recorded in 1 cm quartz cells vs. methanol R. Laboratory electronic balance RAD WAG AS 200 / C, ultrasonic bath Sonorex Digitec DT100H and measuring glassware of grade A were used. Statistical processing and determination of validation parameters were performed in accordance with the requirements of State Pharmacopoeia of Ukraine 2.0 and ICH Q2.&#x0D; Results and Discussions. The spectrophotometric method for the determination of lisinopril by direct measurement of the absorbance of the tested solutions in the ultraviolet region of the spectrum has been developed (lmax=212 nm). Validation parameters including linearity, range of application, specificity, accuracy, precision, limit of detection and limit of quantification, robustness were calculated for the proposed analytical procedure. The correctness of the analytical method was proved by calculating the complete uncertainty of the latter. The calculated uncertainty of sample preparation (DSP) for the determination of lisinopril in tablets was 2.46%. It was established that the maximum contribution to the uncertainty of sample preparation for operations of the quantification of lisinopril in tablets, make the operations of lisinopril CRS sampling and aliquots pipetting. The total uncertainty of the analytical procedure (DAs) in the analysis of the drug was 2.56%. The predicted complete uncertainty of the analysis results did not exceed critical values (DAs=2.56 % £ maxDAs=3.2 %), the method is correct. The specificity is proved by the absence of interfering influence of excipients due to nonoccurence of absorption at the analytical wavelength in the analysis of methanolic extract of placebo-tested tablets, Beers law was obeyed in the ranges of 20-100 mg / ml. The least squares method was used for statistical processing of the results. Regression analysis yielded the following calibration equation: y=26,791x-0,4398. The limit of detection and the limit of quantification were 2,3 і 6,9 mg/ml. Robustness of the method was estimated by studying of absorbance stability changes of tested solutions over time. Robustness was assessed by studying the absorbance stability of the tested solutions over time. It was found that freshly prepared solutions should be used within 100 min. Developed procedure for lisinopril determination in pure substance and tablet dosage form proved to be an excellent green analysis according to analytical eco-scale.&#x0D; Conclusions. Fast, simple, reliable, cost-effective, in accordance with the principles of "green" chemistry spectrophotometric method for determination of lisinopril in pure substance and tablets has been proposed. Validation of the analytical procedure on the parameters of linearity, application range, specificity, accuracy, precision, robustness, limit of detection and limit of quantification was carried out. The complete uncertainty of the analytical procedure at the level of 2.56% was obtained, which proves the possibility of obtaining correct analysis results in other laboratories.

Research the influence of excipients on the technological properties of captopril fast dissolving films

Drug-loaded films are of great interest among fast-dissolving drug-delivery systems. The creation of fast-dissolving films for the treatment of cardiovascular diseases is important.The first inhibitor of angiotensin-converting enzyme to appear on the world market was captopril, which is used to treat hypertension, chronic heart failure and others. Captopril has an antihypertensive effect, which manifests itself within 5–15 minutes after sublingual administration.&#x0D; The aim of our study was to develop the technology of captopril fast dissolving films by solvent casting method and analyze the influence of groups of excipients on technological properties of the films.&#x0D; The influence of the character of polymers, plasticizers, disintegrants and sweeteners on the technological properties of experimental batches of captopril fast dissolving films was studied. Such technological indicators as uniformity of weight, thickness, swelling index,tensile strength, elongationand disintegration time were studied.&#x0D; The influence of excipients' composition on the technological indicators of captopril fast dissolving films has been researched. It was found out that the effect of the type of polymer had the decisive influence on all parameters of films.The selected plasticizer determined the elasticity (films' elongation), film thickness and weight variation. Optimal values of the average weight and thickness of captopril films are provided by the use of a polymer in the combination of HPMC with PEG 4000 or a combination of HPMC with PEG 6000, as a plasticizer – glycerin or PEG 400. The best results of films' swelling were obtained with the introduction of HPMC brands Metolose® 90 SH 100 000 or Metolose® 65 SH 50, Polyplasdone XL-10 crospovidone, propylene glycol and sorbitol. The disintegration time less than 3 min was observed in all investigated film compositions, except those containing PVA. The highest value of tensile strength for captopril films was obtained using HPMC brand Metolose® 65 SH 50 or Metolose®90 SH 100 000.&#x0D; Using the desirability function, the optimal excipients within the studied groups were selected.It has been established that the optimal values of the technological parameters of captopril films can be achieved using Hydroxypropyl MethylcelluloseVivapharm® E15, polyethylene glycol 400, sodium starch glycolate and sorbitol.

Fused Deposition Modeling as a Possible Approach for the Preparation of Orodispersible Tablets.

Additive manufacturing technologies are considered as a potential way to support individualized pharmacotherapy due to the possibility of the production of small batches of customized tablets characterized by complex structures. We designed five different shapes and analyzed the effect of the surface/mass ratio, the influence of excipients, and storage conditions on the disintegration time of tablets printed using the fused deposition modeling method. As model pharmaceutical active ingredients (APIs), we used paracetamol and domperidone, characterized by different thermal properties, classified into the various Biopharmaceutical Classification System groups. We found that the high surface/mass ratio of the designed tablet shapes together with the addition of mannitol and controlled humidity storage conditions turned out to be crucial for fast tablet’s disintegration. As a result, mean disintegration time was reduced from 5 min 46 s to 2 min 22 s, and from 11 min 43 s to 2 min 25 s for paracetamol- and domperidone-loaded tablets, respectively, fulfilling the European Pharmacopeia requirement for orodispersible tablets (ODTs). The tablet’s immediate release characteristics were confirmed during the dissolution study: over 80% of APIs were released from printlets within 15 min. Thus, this study proved the possibility of using fused deposition modeling for the preparation of ODTs.