Y-Site Compatibility Studies of Parenteral Nutrition and Other Intravenous Medications in Neonatal and Pediatric Patients: A Review of the Literature Evidence.

BACKGROUND: Polytherapy in neonatal and pediatric patients requiring parenteral nutrition (PN) administration is a challenging task. Due to limited intravenous access, the Y-site administration of medication with PN admixtures is sometimes inevitable. AIM: This review aims to summarize the evidence on the compatibility of the Y-site of intravenous medications and PN admixtures in neonatal and pediatric settings. METHODS: A literature review of the PubMed database was conducted. Articles published between January 1995 and November 2023 concerning the compatibility of intravenous medications in pediatric-dose PN admixtures or with intravenous lipid emulsions only were included. Studies concerning the compatibility/stability of the ingredients of PN admixtures and those concerning unapproved medications were excluded. Based on the methodology used, the quality of the research was assessed. RESULTS: A total of fifteen studies were explored. Among fifty-five different drug substances assessed in the research reviewed, 56% (31/55) were found to be compatible, 13% (7/55) were assigned as incompatible, and for 31% (17/55), the data were ambiguous. None of the studies demonstrated an "A" grade (very high quality), and the grades "B", "C", and "D" were assigned to four, six, and five studies, respectively. The compatibility data are presented in two tables, the first concerning the simultaneous administration of medications with 2-in-1 PN formulations (without lipids) and the second, with 3-in-1 formulations (with lipids) and lipid emulsions. CONCLUSIONS: This review presents data on compatibilities between intravenously administered medications and PN mixtures intended for neonates and pediatric patients found in the PubMed database. It should be highlighted, however, that this work has some limitations. The clinical decisions on the simultaneous administration of intravenous medication with PN admixtures should be based not only on this review (including assessment of the quality of evidence) but also on manufacturer data, available electronic databases, and incompatibility data for PN admixtures dedicated to adult patients.

Electron Beam Radiation as a Safe Method for the Sterilization of Aceclofenac and Diclofenac-The Usefulness of EPR and 1H-NMR Methods in Determination of Molecular Structure and Dynamics.

Diclofenac (DC) [2-(2,6-Dichloroanilino)phenyl]acetic acid,) and aceclofenac (AC) 2-[2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetyl]oxyacetic acid in substantia were subjected to ionizing radiation in the form of a beam of high-energy electrons from an accelerator in a standard sterilization dose of 25 kGy and higher radiation doses (50-400 kGy). We characterized non-irradiated and irradiated samples of DC and AC by using the following methods: organoleptic analysis (color, form), spectroscopic (IR, NMR, EPR), chromatographic (HPLC), and others (microscopic analysis, capillary melting point measurement, differential scanning calorimetry (DSC)). It was found that a absorbed dose of 50 kGy causes a change in the color of AC and DC from white to cream-like, which deepens with increasing radiation dose. No significant changes in the FT-IR spectra were observed, while no additional peaks were observed in the chromatograms, indicating emerging radio-degradation products (25 kGy). The melting point determined by the capillary method was 153.0 °C for AC and 291.0 °C for DC. After irradiation with the dose of 25 kGy for AC, it did not change, for DC it decreased by 0.5 °C, while for the dose of 400 kGy it was 151.0 °C and 286.0 °C for AC and DC, respectively. Both NSAIDs exhibit high radiation stability for typical sterilization doses of 25-50 kGy and are likely to be sterilized with radiation at a dose of 25 kGy. The influence of irradiation on changes in molecular dynamics and structure has been observed by 1H-NMR and EPR studies. This study aimed to determine the radiation stability of DC and AC by spectrophotometric, thermal and chromatographic methods. A standard dose of irradiation (25 kGy) was used to confirm the possibility of using this dose to obtain a sterile form of both NSAIDs. Higher doses of radiation (50-400 kGy) have been performed to explain the changes in DC and AC after sterilization.

Toward Safe Pharmacotherapy: The Interplay between Meropenem and Parenteral Nutrition Admixtures.

Simultaneous administration of parenteral nutrition (PN) admixtures with intravenous antibiotics is a common clinical problem. Coadministration of drugs incompatible with PN admixture may affect its stability, especially in the context of lipid droplet size, which is a crucial parameter for patient safety. In the present study, we investigate the in vitro compatibility of meropenem (Meropenem 1000, MPM) with five commercial PN admixtures used worldwide: Kabiven, Olimel N9E, Nutriflex Lipid Special, Nutriflex Omega Special, and SmofKabiven. The appropriate volumetric ratios, reflecting their clinical practice ratios, were used to prepare the MPM-PN admixture samples. Physicochemical properties of MPM-PN admixtures samples were determined upon preparation and after four hours of storage. The pH changes for all MPM-PN admixtures samples did not exceed the assumed level of acceptability and ranged from 6.41 to 7.42. After four hours of storage, the osmolarity changes were ±3%, except MPM-Olimel N9E samples, for which differences from 7% to 11% were observed. The adopted level of acceptability of changes in zeta potential after four hours of storage (±3 mV) was met for MPM-Kabiven, MPM-Nutriflex Lipid Special, and MPM-Nutriflex Omega Special. The mean droplet diameter for all samples was below 500 nm. However, only in the case of Nutriflex Lipid Special and Nutriflex Omega Special, the addition of MPM did not cause the formation of the second fraction of lipid droplets. The coadministration of MPM via Y-site with Kabiven, Olimel N9E, and Smofkabiven should be avoided due to osmolarity fluctuations (MPM-Olimel), significant differences in zeta potential (MPM-Olimel, MPM-Smofkabiven), and the presence of the second fraction of lipid droplets >1000 nm (MPM-Kabiven, MPM-Olimel, and MPM-Smofkabiven). The assumed acceptance criteria for MPM compatibility of MPM with PN admixtures were met only for Nutriflex Lipid Special and Nutriflex Omega Special in 1:1, 2:1, and 4:1 volume ratios.

Compatibility of intravenous metronidazole with some all-in-one parenteral nutrition regimens.

OBJECTIVES: Supplementation of parenteral nutrition (PN) admixtures with other parenteral drugs may be desired especially in the case of polypharmacy and limited vascular access. Metronidazole (MTZ) is administered in surgical and critically ill patients often requiring concomitant nutritional therapy in the form of parenteral nutrition. The aim of the study was to evaluate the possibility of the concomitant administration of MTZ with PN admixtures from one container. METHODS: MTZ (1500 mg) was combined with six different PN admixtures and stored for 7 days before the simulation of administration. The mean droplet size (MDS) of the lipid emulsion, zeta potential, color, and pH of the tested samples were determined every 24 h. The content of MTZ was determined by the high-performance liquid chromatography method within the same time frames. RESULTS: PN admixtures supplemented with MTZ were characterized by a pH range from 6.19 to 6.38 and zeta potential range from -21.6 mV to -8.8 mV. For all samples the pharmacopeial criteria for intravenously administered emulsions were met: The visual inspection showed no sign of emulsion destabilization or precipitation, and the MDS was <500 nm. The MTZ content remained >90% of the initial value throughout the whole study period. CONCLUSIONS: Results showed the physicochemical compatibility and stability of PN admixtures supplemented with MTZ at the dose of 1500 mg. Such formulations can be stored at a temperature of 5°C for up to 7 d before administration to the patient.

Stability studies of parenteral nutrition with a high dose of vitamin C.

BACKGROUND: Postoperative administration of parenteral nutrition has become routine management in patients with gastrointestinal cancer. Providing patient the complete parenteral nutrition containing not only the macronutrients and electrolytes but also adequate doses of vitamins is a significant issue of nutritional therapy. The aim of the study was to develop parenteral nutrition containing a high dose of vitamin C (500 mg) and evaluate their stability. METHODS: Five compositions of parenteral nutrition were developed and stored for seven days in three different conditions. Physical stability studies including visual examination and determination of pH, size of lipid droplets (using dynamic laser scattering method), and zeta potential (using laser Doppler electrophoresis method) were performed for all studied parenteral nutrition with and without vitamin C immediately after preparation and after storage. The content of vitamin C was determined using high-performance liquid chromatography (HPLC) method. RESULTS: The addition of vitamin C to parenteral nutrition did not affect its physical stability. Degradation of vitamin C in parenteral nutrition occurred according to first-order kinetics reaction. The content of vitamin C remained above 90% of zero-time content within the first 24 h for each studied parenteral nutrition compositions stored at 4°C and 25°C with light protection. CONCLUSIONS: Vitamin C added to parenteral nutrition was unstable regardless of the storage conditions nor parenteral nutrition compositions. However, for the first 24 h, the content of vitamin C remained in the pharmacopoeial limit. Therefore, supplementation of parenteral nutrition admixtures with vitamin C in the dose of 500 mg is possible in the condition of administration to the patients within the first 24 h.

Modeling of the irradiation effect on some physicochemical properties of metoprolol tartrate for safe medical uses.

The effect of gamma-irradiation and ionizing radiation (high-energy electrons beam) on the physicochemical properties of metoprolol tartrate at the solid phase and aqueous solution, has been investigated in the present study to model some properties affected by absorbed doses and to reveal some interesting mutual causal correlation. The proposed some interesting models can be adapted to other experimental conditions, and the newly obtained values of the adjustable parameters could be an excellent criterion of the state quality of the metoprolol tartrate or for other additional interpretations. The peculiar behaviour of variation of physicochemical properties against dose leads us to confirm the suggested optimized doses mentioned in previous work, for sterilization and safe medical uses.

Stability of high-dose thiamine in parenteral nutrition for treatment of patients with Wernicke's encephalopathy.

BACKGROUND & AIMS: Wernicke's encephalopathy is associated mainly with malnourishment in alcohol-dependent patients but can be caused also by cancer, Crohn's disease, gastrointestinal surgery or prolonged parenteral nutrition (PN) without adequate supplementation of vitamins. The disorder, with a significant mortality rate of up to 20%, is often associated with the underlying disease and intensifies after administration of non-supplemented PN. Thus, it seems justified to add thiamine to PN admixtures prepared for parenterally fed patients. Due to the lack of data on the stability of thiamine in PN admixtures at concentrations exceeding 60 mg/L, we decided to determine the possibility of adding a high dose of thiamine (800 mg per bag, 320 mg/L) to PN admixtures in order to treat Wernicke's encephalopathy in malnourished patients. METHODS: The study aimed to assess the stability of the physical properties of PN admixtures (pH, zeta potential, particle size) and to determine thiamine content using an HPLC method. RESULTS: Thiamine was found to degrade regardless of the PN admixture composition and storage conditions. The highest decrease in thiamine content was observed at room temperature without light protection whereas the lowest at a temperature of 4 ± 1 °C with light protection. CONCLUSIONS: The treatment of Wernicke's encephalopathy in parenterally fed patients is possible with the use of high thiamine doses (800 mg) added to PN admixtures without a decrease in the drug content above 10% within the first 24 h. It should be emphasized that thiamine as a photosensitive drug must be stored and administered under conditions ensuring light protection.

Development, Validation, and Stability Assessment Application of RP-HPLC-DAD Method for Quantification of Ampicillin in Total Parenteral Nutrition Admixtures.

BACKGROUND: The administration of total parenteral nutrition (TPN) is a common procedure in intensive care units, where the concomitant use of other intravenous medication is frequently needed. One of the particularly dangerous complications for neurosurgical patients is meningitis, for which high doses of ampicillin (AMP) are used. In such cases, the addition of AMP to TPN admixtures would be a desirable procedure. Thus, the AMP determination method in TPN admixture was developed and validated. METHODS: An isocratic HPLC analysis was performed on a LiChrospher C18 end-capped column (250 mm, 4.6 mm, 5 µm) with a C18 pre-column (LiChrospher 100, 4 mm, 5 µm). The flow rate was 1.0 mL min-1 and the detection wavelength was 230 nm. System suitability parameters, such as capacity factor, numbers of the theoretical plate, asymmetry factor, as well as validation parameters, including method precision, accuracy, linearity, selectivity, and robustness, were set up. RESULTS: The method was shown to be linear, precise, accurate, specific, and robust, and it can be used for the quantitative analysis of AMP in TPN admixtures. CONCLUSIONS: The degradation of AMP in the TPN admixtures occurred according to first order kinetics. The degradation rate was high and dependent on the composition of the mixture and the storage conditions (t0.5 varied from 142.44 h to 300.45 h).

Stability studies of two compounded solutions potentially used in tumor lysis syndrome.

OBJECTIVE: The aim of the study was to determine the stability of two non-commercially produced solutions: 1.68% sodium bicarbonate in 5% glucose (BIC solution) and 1.6% calcium chloride in 0.9% sodium chloride (CAL solution), which can be used to treat tumor lysis syndrome. One of the ways to treat the tumor lysis syndrome is to irrigate patients, alkalinize the urine through the supply of BIC solution or continuous hemodialysis with regional citrate anticoagulation, using a CAL solution. METHOD: The study took place in two independent hospital pharmacies. Fifty samples of each solution were prepared under aseptic conditions, then the concentration of sodium and calcium ions was determined and microbiological purity tests were carried out. The tests were performed on the day of sample preparation and after seven days of storage at 4 ± 1℃. RESULTS: The obtained results showed that applied preparation method was precise and accuracy. The average concentration of sodium ions in BIC solutions ranged from 187.7 to 185.26 mmol/L on 1st and 7th day, respectively. The average concentration of calcium ions in CAL solution ranged from 68.92 to 68.80 mmol/L on 1st and 7th day, respectively. None of the samples were microbiologically contaminated. CONCLUSION: Studied solutions for infusion were characterized by good chemical and microbiological stability when prepared in a clean room and stored at 4 ± 1℃.

Effect of Lipid Emulsion on Stability of Ampicillin in Total Parenteral Nutrition.

BACKGROUND: Ampicillin (AMP) is frequently administered parenterally in critically ill patients with meningitis or endocarditis. Many of them require parallel infusion of total parenteral nutrition (TPN) admixtures. The aim of the study was to determine the physicochemical stability of AMP in TPN admixtures. METHODS: AMP was added to two formulations of TPN admixtures differing in the lipid emulsion (Lipofundin® MCT/LCT 20% or LIPIDem®). Samples were stored at 4 ± 1 °C with light protection, and at 25 ± 1 °C with and without light protection to assess the impact of temperature and light on formulation stability. Every 24 h the pH, zeta potential, mean droplet diameter (MDD) of a lipid emulsion, and AMP concentration using HPLC method were determined. The assessment of stability and compatibility of TPN admixtures with vitamins and trace elements was carried out immediately after preparation and after 24 h of storage. RESULTS: The addition of AMP as well as vitamins and trace elements to the TPN admixtures did not affect their physical stability. An increase in the pH value of approx. 0.6 and reduction of zeta potential were observed. The MDD of the lipid emulsions was below the limit of 500 nm (dynamic light scattering (DLS) method) and no fat droplets greater than 525 nm were observed (light diffraction (LD) method). The content of AMP after the first 24 h was within the acceptable limit of 90% for TPN admixtures stored at 4 ± 1 °C and 25 ± 1 °C with light protection. CONCLUSIONS: The results showed that co-administration of AMP in the same bag with TPN admixture at the tested dose is possible when used ex tempore and with light protection.

Formulation and characterization of EGCG for the treatment of superficial bladder cancer.

In the United States, the annual incidence of bladder cancer is approximately 70,000 new cases, with a mortality rate of approximately 15,000/year. The most common subtype (70%) of bladder cancer is superficial, namely hte non-muscle invasive disease form limited to the urothelium. The rate of progression and recurrence is up to 40 and 70%, respectively. Urothelial cell carcinoma of the bladder is typically treated with transurethral resection. The cancerous cells can float onto the adjacent epithelium, increasing the risk of recurrence. The standard of care is to offer adjuvant intravesical agents to reduce the risk of progression and recurrence. Current intravesical treatments are costly and are associated with special biohazard handling protocols. Patients are treated with intravesical therapy with bacillus Calmetter­Guerin (BCG) bacterium, or mitomycin C (MMC) following resection, both of which can cause moderate to severe side-effects which are rarely life-threatening. We previously examined the efficacy of epigallocatechin-3-gallate (EGCG) in comparison with MMC to prevent tumor cell implantation/growth in an animal model of superficial bladder cancer. Experiments revile that EGCG is slightly more effective than MMC at decreasing tumor cell implantation and consequent cancer growth in a bladder. This treatment requires the stringent sterile requirement of EGCG. EGCG can be unstable when sterilized at high temperatures. Thus, we evaluated two low temperature sterilization methods, such as ionizing radiation or the filtration method followed by freeze-drying. Both methods ensure the sterility of the sample; however, infrared and HPLC analysis revealed a slightly better stability of irradiated EGCG over the filtration method. The concentration of stable free radicals following irradiation was low, which are unlikely to exert any damaging effects to EGCG. Therefore, we consider that radiation will be the preferred method of EGCG sterilization, and that this may prove useful for the effective use of EGCG in the treatment of bladder cancer.

Beta-Blockers: Current State of Knowledge and Perspectives.

It has been over half a century since propranolol, the first beta-blocker, was developed for medical treatment. Since that time a large number of compounds from this group have been synthesised and many are now in clinical use. The structure, function, pharmacokinetics, and mechanism of beta-blockers have been established. The possibilities for their use in treating different conditions continue to evolve. Since the discovery of later generation beta-blockers, such as carvedilol and nebivolol, the search for new compounds continues, and may include known substances with beta-blocking properties which could extend their therapeutic potential.

Identification of Radiodegradation Products of Acebutolol and Alprenolol by HPLC/MS/MS.

Two therapeutically active compounds from the group of ß-blockers, acebutolol (AC) and alprenolol (AL), in solid form were subjected to ionizing radiation emitted by a beam of high energy electrons from an accelerator with a standard sterilization dose of 25 kGy and in higher doses of 50-400 kGy. The effects of irradiation were detected by chromatographic methods (TLC, HPLC) and a hyphenated method (HPLC/MS/MS). No significant changes in the physicochemical properties of both compounds studied irradiated with 25 kGy were noted, but upon irradiation with the highest dose (400 kGy) the loss of AC and AL content determined by HPLC was 2.79 and 9.12%, respectively. The product of AC decomposition and the two products of AL decomposition were separated and identified by HPLC/MS/MS. It has been established that radiodegradation of AC and AL takes place by oxidation, leading to formation of the products of radiolysis, most probably alcohol derivatives of the ß-blockers studied. The additional product that appears on radiodegradation of AL is probably formed as a result of two simultaneous reactions: oxidation and CH2 group elimination.

The influence of ionizing radiation on itraconazole in the solid state.

The aim of this study was to investigate the ionizing radiation effects, in the form of an electron beam, on itraconazole (ITR) in the solid phase. It was found that the ITR, under the influence of a standard 25 kGy dose of radiation used for the sterilization of drug substances, decomposed at 0.4%. Moreover, a gentle change of colour and a decrease in melting point does not exceed pharmacopoeial standards causing that ITR can be sterilized by radiation method. The use of high 400 kGy radiation doses resulted in a 6.5% decomposition of the ITR and eight radiodegradation products were found. However, with the exception of differential scanning calorimetry (DSC), the X-ray diffraction, Fourier transform infrared spectroscopy (FT-IR) and ultraviolet-visible (UV-vis) methods showed no changes in the form and the morphology of the crystals. The structures of all those compounds were investigated. It was confirmed that the ITR decomposition takes place by dehalogenation (one of Cl atom elimination), the oxidation in isobutyl residue (beside the triazole ring) and C-O bond rupture.

The influence of ionizing radiation, temperature, and light on eplerenone in the solid state.

Eplerenone was subjected to the influence of ionizing radiation in the form of a high-energy electron beam (25-400 kGy), high temperature (90°C RH 0% and 60°C RH 76.4%), and light (6 mln lux h). An HPLC method was used to determine the content of eplerenone and to establish the impurity profile of all samples. As eplerenone was found to be a compound of great resistance to the above stress factors with the exception of high doses of ionizing radiation (≥ 200 kGy) when its degradation was above 1%, it is possible to sterilize eplerenone by radiation method with the standard dose of 25 kGy. Based on the analysis of impurities and degradation products, the mechanism of radiodegradation was demonstrated to differ from the mechanisms of photo- and thermodegradation. The observation that the DSC curves for the nondegraded and degraded samples of eplerenone were significantly different only under exposure to the electron beam confirmed the applicability of DSC for studies of radiolytic degradation of eplerenone.

Comparative analysis of selected beta-blockers.

The suitability and effectiveness of a few spectrophotometric and chromatographic methods (UV, FT-IR, MS, TLC) for differentiating analysis of 6 beta-blockers: acebutolol, alprenolol, atenolol, metoprolol, pindolol and propranolol have been tested.

The effect of ionizing radiation on metoprolol.

The influence of ionising radiation on physico-chemical properties of metoprolol tartrate (MT) in solid phase was studied. The compound was irradiated by radiation produced by a beam of high-energy electrons in an accelerator, in doses from 25 to 400 kGy, and the possible changes in the samples were detected by organoleptic analysis (colour, forms, clarity), chromatographic and spectrometric methods. Already at the standard sterilisation dose of 25 kGy, the presence of free radicals (0.3764 × 10(16) spin/g) and a decrease in the melting point by 1°C were noted. At higher doses of irradiation products of radiolysis appeared (100 kGy) and the colour was changed from white to pale cream (200 kGy). Our observation was that with increasing mass loss of MT after irradiation with 100, 200 and 400 kGy, the concentration of free radicals increased from 1.0330 to 1.6869 × 10(16) spin/g. The radiolytic yield of total radiolysis was 4.54 × 10(7) mol/J for 100 kGy, 7.42 × 10(7) mol/J for 200 kGy and 4.74 × 10(7) mol/J for 400 kGy. No significant changes were observed in the character of FT-IR spectra, but in UV an increase in intensity of the band at the analytical wavelength was noted. As follows from the results MT shows high radiochemical stability for the typical sterilisation doses 25-50 kGy, and will probably be able to be sterilised by radiation in the dose of 25 kGy.

Influence of e-beam irradiation on sulfamethoxazole in solid state.

The effects of ionizing radiation generated by a beam of electrons, in that doses varied from 25-800 kGy, on the physico-chemical properties of sulfamethoxazole (SMX) in solid state have been studied at room temperature and in the air atmosphere. The changes appearing after the irradiation were detected and evaluated by the spectroscopic methods (UV, IR, MS, EPR), chromatography (TLC and HPLC) and SEM, XRD and DSC. Already the lowest dose of 25 kGy was found to change the color of SMX from white to pale cream; such change became more intense with our increasing the irradiation dose. Products of radiodegradation and decreases in the drug content were detected by TLC and HPLC only after irradiation with 400 kGy. Since the SMX radiolysis products (sulfanilamide and sulfanilic acid) are colorless compounds, it is supposed that the color results from trapping of free radicals in the crystal lattice; the concentration of free radicals was 1.04 × 10(15) spin/g. Our results indicate that the radiolysis of SMX in the solid state caused by e-beams involves breaking of the S-N and N-C bonds. The mean radiolytic yield of this process is G((-SMX)) = 1.89 × 10(-7) mol/J, whereas the yield of formation of the two products of radiolysis is close and equal to 2.18 × 10(-8) mol/J (sulfanilamide) and 2.13 × 10(-8) mol/J (sulfanilic acid).

Effect of radiation sterilization on alprenolol in the solid state studied by high-performance thin-layer chromatography.

The possibility of radiation sterilization of alprenolol (AL) has been studied. Irradiation of AL in solid form with a 25 kGy beam of electrons caused only an insignificant change in color that became more intense with increasing irradiation dose. Moreover, with increasing dose a decrease in pH, the content of water, and the degree of crystallinity were observed. AL in solid form was radiated with a high-energy electron beam (9.96 MeV) at doses from 25-400 kGy and analyzed by HPTLC using the mobile phase methanol-ammonia 25% (99 + 1, v/v). Densitometric analysis was carried out directly from chromatograms at 270 nm. The applied method was validated and characterized by good precision (RSD = 3.95%); good accuracy (80% level 100.15%, 100% level 99.99%, and 120% level 104.44%); and low LOD (LOD = 0.52 microg/zone and LOQ = 1.55 microg/zone). Chromatograms recorded for samples irradiated at the doses of 25 kGy were unchanged, but at higher doses (100-400 kGy) additional peaks corresponding to the radiodegradation products appeared (Rf = 0.24 and Rf = 0.40). The decrease in the concentration of AL was proportional to the applied radiation dose, and for 400 kGy the concentration of AL was 90.23%. The calculated radiolytic yield of the radiodegradation process was G(-AL) = 7.12 x 10(-7) mol/J.

Thermal stability of 1,4-dihydropyridine derivatives in solid state.

The effect of temperature and air humidity on the stability of 7 derivatives of 1,4-dihydropyridine (nifedipine, nisoldipine, nitrendipine, nimodipine, nicardipine, felodipine and amlodipine) in solid state has been studied by accelerated testing. Quantitative analysis of the compounds studied was made by UV spectrophotometry, identification of the thermodegradation products and reference to the standard were made by thin layer chromatography (TLC), UV spectra and the reaction with KMnO4. Thermodegradation of the derivatives studied was found not to occur in dry air, whereas at air humidity it occurred according to the first order reaction at a similar rate for all derivatives. The main product of thermodegradation of the derivatives with the nitro substituent was a nitrozoderivative formed as a result of dihydropyridine ring aromatisation accompanied by water molecule elimination.