The technological process of production of biosimilars determines the degree of biosimilarity to the original biological drug. In particular, the focus is on the similarity of immunogenic responses. The primary endpoint of our retrospective study was to find the differences in SARS-CoV-2 antibody amount between patients treated with original adalimumab and biosimilar adalimumab MSB11022 (Idacio) and the differences in the SARS-CoV-2 antibody amount between patients treated with and without biological treatment. We collected the gender, autoimmune disease type, age, and treatment data of the patients in the outpatient clinic MEDICAL PLUS, s.r.o., Uherske Hradiste. These patients suffer from autoimmune rheumatic diseases. All patients received the mRNA vaccine (Pfizer/BioNTech - BNT162b2), with a 21-day (interquartile range, 21-24) gap between the two vaccinations. Patients receiving adalimumab were able to develop cellular immune responses after the second vaccination dose, as well as the individuals without adalimumab. In the period of 6-23 weeks after the second vaccination dose (D63 - D182), the SARS-CoV-2 antibody levels did not change significantly in the patients receiving the original adalimumab, while in the patients receiving biosimilar adalimumab a significant decrease was revealed. A statistically significant difference in the SARS-CoV-2 antibody amount between the patients without biological treatment (median: 504.3 U/mL) and with biological treatment (Original and Biosimilar - median: 47.2 and 28.2 U/mL, respectively) was confirmed on day 182. According to our observation, the effect of the treatment type on the increase/decrease of antibodies over time is dominant, while the impact of other variables (gender, methotrexate treatment, autoimmune disease type, and age) was confirmed as insignificant or minor.
Treating oral diseases remains challenging as API is quickly washed out of the application site by saliva turnover and mouth movements. In situ gels are a class of application forms that present sol-gel transition's ability as a response to stimuli. Their tunable properties are provided using smart polymers responsible for stimuli sensitivity, often providing mucoadhesivity. In this study, antimicrobial in situ gels of thermosensitive and pH-sensitive polymers loaded with silver nanoparticles were prepared and evaluated. The nanoparticles were prepared by green synthesis using Agrimonia eupatoria L. extract. According to the data analysis, the in situ gel with the most promising profile contained 15â¯% of Pluronic® F-127, 0.25â¯% of methylcellulose, and 0.1â¯% of Noveon® AA-1. Pluronic® F-127 and methylcellulose significantly increased the viscosity of in situ gels at 37⯰C and shear rates similar to speaking and swallowing. At 20⯰C, a behavior close to a Newtonian fluid was observed while being easily injectable (injection force 13.455⯱â¯1.973â¯N). The viscosity of the formulation increased with temperature and reached 2962.77⯱â¯63.37 mPa·s (37⯰C). A temperature increase led to increased adhesiveness and rigidity of the formulation. The critical sol-gel transition temperature at physiological pH was 32.65⯱â¯0.35⯰C. 96.77⯱â¯3.26â¯% of Ag NPs were released by erosion and dissolution of the gel after 40â¯min. The determination of MIC showed effect against E. coli and S. aureus (0.0625â¯mM and 0.5000â¯mM, respectively). The relative inhibition zone diameter of the in situ gel was 73.32⯱â¯11.06â¯% compared to gentamicin sulfate. This work discusses the optimization of the formulation of novel antibacterial in situ gel for oromucosal delivery, analyses the impact of the concentration of excipients on the dependent variables, and suggests appropriate evaluation of the formulation in terms of its indication. This study offers a promising dosage form for local treatment of oral diseases.
Metal Nanoparticles , Poloxamer , Poloxamer/chemistry , Silver , Escherichia coli , Staphylococcus aureus , Temperature , Gels/chemistry , Methylcellulose
Introduction: Due to the intensification of fish farming and the associated spread of antimicrobial resistance among animals and humans, it is necessary to discover new alternatives in the therapy and prophylaxis of diseases. Probiotics appear to be promising candidates because of their ability to stimulate immune responses and suppress the growth of pathogens. Methods: The aim of this study was to prepare fish feed mixtures with various compositions and, based on their physical characteristics (sphericity, flow rate, density, hardness, friability, and loss on drying), choose the most suitable one for coating with the selected probiotic strain Lactobacillus plantarum R2 Biocenol™ CCM 8674 (new nom. Lactiplantibacillus plantarum). The probiotic strain was examined through sequence analysis for the presence of plantaricin- related genes. An invented coating technology based on a dry coating with colloidal silica followed by starch hydrogel containing L. plantarum was applied to pellets and tested for the viability of probiotics during an 11-month period at different temperatures (4°C and 22°C). The release kinetics of probiotics in artificial gastric juice and in water (pH = 2 and pH = 7) were also determined. Chemical and nutritional analyses were conducted for comparison of the quality of the control and coated pellets. Results and discussion: The results showed a gradual and sufficient release of probiotics for a 24-hour period, from 104 CFU at 10 mi up to 106 at the end of measurement in both environments. The number of living probiotic bacteria was stable during the whole storage period at 4°C (108), and no significant decrease in living probiotic bacteria was observed. Sanger sequencing revealed the presence of plantaricin A and plantaricin EF. Chemical analysis revealed an increase in multiple nutrients compared to the uncoated cores. These findings disclose that the invented coating method with a selected probiotic strain improved nutrient composition and did not worsen any of the physical characteristics of pellets. Applied probiotics are also gradually released into the environment and have a high survival rate when stored at 4°C for a long period of time. The outputs of this study confirm the potential of prepared and tested probiotic fish mixtures for future use in in vivo experiments and in fish farms for the prevention of infectious diseases.
Probiotics have been used in human and veterinary medicine to increase resistance to pathogens and provide protection against external impacts for many years. Pathogens are often transmitted to humans through animal product consumption. Therefore, it is assumed that probiotics protecting animals may also protect the humans who consume them. Many tested strains of probiotic bacteria can be used for individualized therapy. The recently isolated Lactobacillus plantarum R2 Biocenol™ has proven to be preferential in aquaculture, and potential benefits in humans are expected. A simple oral dosage form should be developed to test this hypothesis by a suitable preparation method, i.e., lyophilization, allowing the bacteria to survive longer. Lyophilizates were formed from silicates (Neusilin® NS2N; US2), cellulose derivates (Avicel® PH-101), and saccharides (inulin; saccharose; modified starch® 1500). They were evaluated for their physicochemical properties (pH leachate, moisture content, water absorption, wetting time, DSC tests, densities, and flow properties); their bacterial viability was determined in conditions including relevant studies over 6 months at 4 °C and scanned under an electron microscope. Lyophilizate composed of Neusilin® NS2N and saccharose appeared to be the most advantageous in terms of viability without any significant decrease. Its physicochemical properties are also suitable for capsule encapsulation, subsequent clinical evaluation, and individualized therapy.
Inhalation is used for local therapy of the lungs and as an alternative route for systemic drug delivery. Modern powder inhalation systems try to target the required site of action/absorption in the respiratory tract. Large porous particles (LPPs) with a size >5 µm and a low mass density (usually measured as bulk or tapped) of <0.4 g/cm3 can avoid protective lung mechanisms. Their suitable aerodynamic properties make them perspective formulations for deep lung deposition. This experiment studied the effect of spray-drying process parameters on LPP properties. An experimental design of twelve experiments with a central point was realized using the Box-Behnken method. Three process parameters (drying temperature, pump speed, and air speed) were combined on three levels. Particles were formed from a D-mannitol solution, representing a perspective material for lung microparticles. The microparticles were characterized in terms of physical size (laser diffraction), aerodynamic diameter (aerodynamic particle sizer), morphology (SEM), and densities. The novelty and main goal of this research were to describe how the complex parameters of the spray-drying process affect the properties of mannitol LPPs. New findings can provide valuable data to other researchers, leading to the easy tuning of the properties of spray-dried particles by changing the process setup.
Films are thin, flexible, and transparent wound dressings. They can be prepared from both synthetic and natural materials. In practice, synthetic polyurethane dominates, but research is mainly focused on substances of natural origin. An endogenous substance with excellent filmforming properties, which is involved in the wound healing process, is collagen. However, collagen films themselves have weak mechanical properties, which can be improved by, among other things, combining collagen with other materials. Such material could be carboxymethylcellulose, which has been shown to affect wound healing positively. Films consisting only of CMC also have weak mechanical properties, so combining both materials seems to be a suitable solution to the given problems, and a wound dressing with many beneficial properties for wound healing could be created. Therefore, our experiment aimed to prepare composite films for wound therapy consisting of a combination of collagen and CMC. The films were prepared by the solvent evaporation method, and their properties were compared with those formed only by CMC. In both cases, films with suitable organoleptic, physicochemical, and application properties for wound therapy were produced. The composite films showed lower absorption capacity and better mechanical resistance compared to those formed only by CMC. The combination of collagen and CMC in composite films intended for wound therapy has thus resulted in improved properties of the resulting dressing and holds potential for further research.
Bandages , Carboxymethylcellulose Sodium , Collagen , Wound Healing , Polyurethanes
Pharmaceutical technology offers several options for protecting substances from acidic environments, such as encapsulation in enteric capsules or dosage form with enteric coating. However, commercial enteric capsules do not always meet limits for pharmacopeial delayed release, and the coating process is generally challenging. Preparing small enteric batches suitable for clinical use is, therefore, an unsolved problem. This experiment offers a simple coating process of DRcapsTM capsules based on hypromellose (HPMC) and gellan gum to achieve small intestine administration. In addition, DRcapsTM capsules were compared to hard gelatin capsules to evaluate the suitability of the coating method. Both capsules were immersed in dispersions of Eudragit® S 100, Acryl-EZE®, and Cellacefate at concentrations of 10.0, 15.0, and 20.0% and dried. Coated capsules were evaluated by electron microscopy, disintegration, and dissolution test with a two-step pH change (from 1.2 to 6.8, then to 7.5) to simulate passage through the digestive tract. DRcapsTM capsules coated with Eudragit® S and Cellacefate achieved acid resistance. While samples coated with Eudragit® S released their contents within 360 min at pH 6.8 (small intestine), regardless of polymer concentration, capsules with 15.0 and 20.0% coatings of Cellacefate released content at pH 7.5 (colon) within 435 and 495 min, respectively.
Collagen is essential as a physiological material in wound healing, so it is often used in wound management, mainly as a lyophilisate. Collagen also has excellent film-forming properties; unfortunately, however, its utilisation as a film wound dressing is limited because of its weak mechanical properties, especially in its wet state. For this reason, modifications or combinations with different materials are investigated. The combination of collagen with partially modified microfibrillar carboxymethylcellulose (CMC), which has not previously been described, provided a new possibility for strengthening collagen films and was the aim of this work. The collagen-CMC films based on three types of collagens, two plasticizers and two collagen. Plasticiser ratios were prepared using the solvent casting method; partially modified CMC served here as both a film-forming agent and a filler, without compromising the transparency of the films. The presence of microfibrils was confirmed microscopically by SEM. Organoleptic and physicochemical evaluation, especially in terms of practical application on wounds, demonstrated that all the samples had satisfactory properties for this purpose even after wetting. All the films retained acidic pH values even after 24 h, with a maximum of 6.27 ± 0.17, and showed a mild degree of swelling, with a maximum of about 6 after 24 h.
A method of preparing tablets called liquisolid technique is currently emerging. In these formulations, an important role is played by porous carriers, which are the basic building blocks of liquisolid systems (LSSs). The most common are microcrystalline cellulose (MCC), magnesium aluminometasilicates, silica aerogels, mesoporous silicates, clays, etc. In this study, magnesium aluminometasilicate is used to prepare modified LSS formulations with plant extracts as model drugs dissolved in water (W) or ethanol (E). The modification involves drying tablets in a microwave (MW) and hot air dryer (HA) for a specified period. Powder blends and tablets were evaluated for physical properties, and their antioxidant activity (AA) was measured in a modified dissolution by ferric reducing antioxidant power assay (FRAP). PLS and ANOVA were used to compare tablets properties depending on the composition and technology. The experiment is based on a previous one, in which the plant extracts were processed into tablets using a similar method. Therefore, extending the study to include more plants and the robust statistical evaluation and comparison of the products was a procedure to justify the suitability of the presented method for a wide range of liquid plant extracts. As a result, we obtained tablets with excellent physical properties, including a short disintegration and dissolution, which is problematic in tableted extracts.
Orodispersible films are an innovative dosage form. Their main advantages are the application comfort and the possibility of personalization. This work aimed to evaluate the influence of different drying times on the properties of orodispersible films of various thicknesses, prepared in two different semisolid extrusion 3D printing setups. In the first experiment, drying times were dependent on the overall print time of each batch. In the second setup, the drying time was set equal according to the longest one. The evaluated parameters were films' weight uniformity, thickness, moisture content, surface pH, disintegration time, hardness, and tensile strength. Upon statistical comparison, significant differences in the moisture content were found, subsequently affecting the disintegration time. Moreover, statistically significant differences in films' mechanical properties (hardness, tensile strength) were also described, proving that moisture content simultaneously affects film plasticity and related properties. In conclusion, a mutual comparison of the manufactured orodispersible films showed that the drying time affects their physical and mechanical properties. The in-process drying setup was proved to be sufficient while allowing quicker manufacturing.
Pharmaceutical technology offers various dosage forms that can be applied interdisciplinary. One of them are spherical pellets which could be utilized as a carrier in emerging second-generation detection tubes. This detection system requires carriers with high specific surface area (SSA), which should allow better adsorption of toxic substances and detection reagents. In this study, a magnesium aluminometasilicate with high SSA was utilized along with various concentrations of volatile substances (menthol, camphor and ammonium bicarbonate) to increase further the carrier SSA after their sublimation. The samples were evaluated in terms of physicochemical parameters, their morphology was assessed by scanning electron microscopy, and the Brunauer-Emmett-Teller (BET) method was utilized to measure SSA. The samples were then impregnated with a detection reagent o-phenylenediamine-pyronine and tested with diphosgene. Only samples prepared using menthol or camphor were found to show red fluorescence under the UV light in addition to the eye-visible red-violet color. This allowed the detection of diphosgene/phosgene at a concentration of only 0.1 mg/m3 in the air for samples M20.0 and C20.0 with their SSA higher than 115 m2/g, thus exceeding the sensitivity of the first-generation DT-12 detection tube.
The utilization of co-processed excipients (CPEs) represents a novel approach to the preparation of orally disintegrating tablets by direct compression. Flow, consolidation, and compression properties of four lactose-based CPEs-Cellactose® 80, CombiLac®, MicroceLac® 100, and StarLac®-were investigated using different methods, including granulometry, powder rheometry, and tablet compaction under three pressures. Due to the similar composition and the same preparation technique (spray drying), the properties of CPEs and their compacts were generally comparable. The most pronounced differences were observed in flowability, undissolved fraction after 3 min and 24 h, energy of plastic deformation (E2), ejection force, consolidation behavior, and compact friability. Cellactose® 80 exhibited the most pronounced consolidation behavior, the lowest values of ejection force, and high friability of compacts. CombiLac® showed excellent flow properties but insufficient friability, except for compacts prepared at the highest compression pressure (182 MPa). MicroceLac® 100 displayed the poorest flow properties, lower ejection forces, and the best mechanical resistance of compacts. StarLac® showed excellent flow properties, the lowest amounts of undissolved fraction, the highest ejection force values, and the worst compact mechanical resistance. The obtained results revealed that higher compression pressures need to be used or further excipients have to be added to all tested materials in order to improve the friability and tensile strength of formed tablets, except for MicroceLac® 100.
Antimicrobial agent abuse poses a serious threat for future pharmacotherapy, including vaginal administration. The solution can be found in simple polymeric systems with inherent antimicrobial properties without the need to incorporate drugs, for instance alginate beads cross-linked by bivalent ions. The main goal of the presented study was to provide improvement on the well-documented cytotoxicity of Cu2+ cross-linked alginate. Alginate beads were prepared by external ionotropic gelation by cross-linking with Cu2+, Ca2+ and Zn2+ ions, separately and in mixtures. Morphological properties, swelling capacity, ion release and efficacy against the most common vaginal pathogens (C. albicans, E. coli, E. faecalis and virus strain-human herpesvirus type 1) were evaluated. The prepared particles (particle size 1455.68 ± 18.71-1756.31 ± 16.58 µm) had very good sphericity (0.86 ± 0.04-0.97 ± 0.06). In mixture samples, Cu2+ hampered second ion loading, and was also released incompletely (18.75-44.8%) compared to the single ion Cu2+ sample (71.4%). Efficacy against the selected pathogens was confirmed in almost all samples. Although anticipating otherwise, ion mixture samples did not show betterment over a Cu2+ cross-linked sample in cytotoxicity-pathogen efficacy relation. However, the desired improvement was found in a single ion Zn2+ sample whose minimal inhibition concentrations against the pathogens (0.6-6.12 mM) were close to, or in the same mathematical order as, its toxic concentration of 50 (1.891 mM). In summary, these findings combined with alginate's biocompatibility and biodegradability give the combination solid potential in antimicrobial use.
The vaginal rings research is almost exclusively focused on rings for human medicine, although the dosage form offers improvement of therapeutic effect in other mammals as well. This contribution studied an effect of varying dimension parameters (diameter 20, 30 or 40 mm; height 3, 4 or 5 mm; width of annulus 5, 7.5 or 10 mm) on mechanical properties and dissolution behaviour of silicone vaginal rings with constant drug amount, intended for use in dogs. Results showed that altering dimensions influenced mechanical properties (compressive force, tensile strength and resistance of removal thread), in vitro drug release and water uptake. The removal thread resistance was increasing with increasing height and width. Compression force was higher for the rings with smaller diameter. The total drug release was increasing with decreasing height and rising diameter, surface area and water uptake during dissolution test. The initial dissolution rate was slower for the rings with higher width. As the best candidate for use in model dog subjects, the ring with 30 mm diameter, 3 mm height and 7.5 mm width was found. These drug-free vaginal rings were further tested in in vivo safety study. The results did not show any major deviation from the physiological conditions. Graphical abstract.
Contraceptive Devices, Female , Animals , Dogs , Drug Liberation , Female , Mechanical Phenomena , Solubility , Tensile Strength , Toxicity Tests
Currently, nerve agents are often used in terrorist attacks or assassinations. In such cases, it is necessary to detect them quickly, accurately and easily right in the field. Detection tubes, which are small devices containing pellets with immobilized cholinesterase and detection reagents, meet these conditions. Their detection mechanism is based on a highly sensitive enzymatic Ellman reaction, when in the absence of cholinesterase inhibitors the pellets develop a visible yellow color, whereas in their presence the carriers retain the original color. The rate of reaction, its sensitivity and the distinct color transition are the key points of the research. In this experiment, double-coated pellets were prepared. The first coating contained the butyrylcholinesterase immobilized in hypromellose, while the second coating consisted of ethylcellulose and triethyl citrate. Based on the properties of such carriers, samples containing lactose dispersed in the ethylcellulose coating were also prepared, which was expected to have an effect on increasing the permeability of the coating and hence the detection rate and color intensity. In addition to selected physicochemical properties, carriers were evaluated for enzyme activity, sensitivity and color transition intensity. Samples showing the best properties were subjected to a 24-months stability test at three different temperatures and humidity.
Butyrylcholinesterase/chemistry , Cellulose/analogs & derivatives , Cholinesterase Inhibitors/isolation & purification , Enzymes, Immobilized/chemistry
Pellets with an immobilized enzyme (acetyl- or butyrylcholinesterase) are the up-to-date type of carriers used for the detection of nerve agents (soman, sarin, tabun, VX, Novichok) and other cholinesterase inhibitors such as organophosphate and carbamate insecticides (parathion, malathion). They are used in the glass detection tubes as a layer containing the enzyme together with the second layer, which contains a colorimetric reagent and substrate. The detection method is based on the visually or spectrophotometrically observable Ellman's reaction, which develops a yellow color in the absence of the cholinesterase inhibitor; otherwise, the detector preserves its original color (preferably white). This reaction occurs very fast and has a high sensitivity to nerve agents but it suffers from an indistinctive color transition from white to yellow. In the presented study, a new approach with the use of the synergic effect of magnesium aluminometasilicate with a high surface area marketed as Neusilin®US2 and a protective semipermeable Eudragit® RL layer was utilized. The prepared pellets have been evaluated for their properties such as the activity of the enzyme, intensity of the developed yellow color, sensitivity to cholinesterase inhibitor physostigmine, which acts as a nerve agent simulant, and physical parameters such as hardness, pycnometric density and sphericity. After the initial evaluation, all samples underwent a stability test under three different storage conditions for 24 months during which they were evaluated at given time points (0, 3, 6, 12 and 24 months). It was found that the prepared samples achieved a much higher intensity of developed yellow color than in the published studies while maintaining similar or better sensitivity, speed of detection and suitable physico-chemical properties.
Cholinesterase Inhibitors/analysis , Nerve Agents/analysis , Acetylcholinesterase/chemistry , Aluminum Compounds/chemistry , Butyrylcholinesterase/chemistry , Colorimetry/methods , Enzymes, Immobilized/chemistry , Magnesium Compounds/chemistry , Polymers/chemistry , Silicates/chemistry , Time Factors
Currently, the method of external ionic gelation for the preparation of alginate particles is successfully used not only in the field of pharmacy and medicine, but also especially in the field of biotechnology. Therefore, the preparation of alginate particles and their subsequent evaluation using principal component analysis was the key task of our experiment. To optimize this method, we focused on the evaluation of the effect of formulation (the polymer concentration, the hardening solution concentration) and process parameters (the outer diameter of the injection needle) on the properties of the resulting beads (yield, sphericity factor, equivalent diameter and swelling capacity at pH 6). Using multivariate data analysis, the major influence on the resulting properties of the prepared particles was confirmed only in sodium alginate concentration. Obtained results verified the reliable and safe potential of the external ionic gelation for preparation alginate-based particulate dosage forms.
Alginates/chemistry , Copper/chemistry , Polymers , Principal Component Analysis
Detection tubes are small devices for the colorimetric enzymatic detection of cholinesterase inhibitors such as sarin, soman, VX nerve agents and substances denoted as Novichok. These detectors contain carriers in the form of pellets with immobilized cholinesterase, substrate and detection reagent. Their advantages are portability, sensitivity and simplicity, enabling fast detection of such compounds from air and water in case of a terrorist attack or war. In general, maintaining the stability of an enzyme for a longer time is very problematic; therefore, its further enhancement is required for safety and financial reasons. In this study, the stability of our patented carriers in the form of pellets with immobilized butyrylcholinesterase containing an increasing amount of the unique sorbent Neusilin® US2 was evaluated. The samples containing Neusilin maintained the stability of the immobilized enzyme for a longer time even at higher temperature and humidity than the currently commercially used carrier without Neusilin, allowing improved detection of nerve agents.
Aluminum Compounds/metabolism , Biosensing Techniques/methods , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/analysis , Colorimetry/methods , Drug Carriers/chemistry , Enzyme Stability/drug effects , Magnesium Compounds/metabolism , Silicates/metabolism , Butyrylcholinesterase/chemistry , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism
The aim of the present study was to investigate the suitability of insoluble Eudragit® water dispersions (NE, NM, RL, and RS) for direct high-shear granulation of very soluble levetiracetam in order to decrease its burst effect from HPMC K100M matrices. The process characteristics, ss-NMR analysis, in vitro dissolution behavior, drug release mechanism and kinetics, texture profile analysis of the gel layer, and PCA analysis were explored. An application of water dispersions directly on levetiracetam was feasible only in a multistep process. All prepared formulations exhibited a 12-hour sustained release profile characterized by a reduced burst effect in a concentration-dependent manner. No effect on swelling extent of HPMC K100M was observed in the presence of Eudragit®. Contrary, higher rigidity of formed gel layer was observed using combination of HPMC and Eudragit®. Not only the type and concentration of Eudragit®, but also the presence of the surfactant in water dispersions played a key role in the dissolution characteristics. The dissolution profile close to zero-order kinetic was achieved from the sample containing levetiracetam directly granulated by the water dispersion of Eudragit® NE (5% of solid polymer per tablet) with a relatively high amount of surfactant nonoxynol 100 (1.5%). The initial burst release of drug was reduced to 8.04% in 30 min (a 64.2% decrease) while the total amount of the released drug was retained (97.02%).
Hypromellose Derivatives , Lactose/analogs & derivatives , Methylcellulose/analogs & derivatives , Nonoxynol , Polymethacrylic Acids , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/pharmacology , Drug Liberation , Hypromellose Derivatives/chemistry , Hypromellose Derivatives/pharmacokinetics , Hypromellose Derivatives/pharmacology , Lactose/chemistry , Lactose/pharmacokinetics , Lactose/pharmacology , Methylcellulose/chemistry , Methylcellulose/pharmacokinetics , Methylcellulose/pharmacology , Nonoxynol/chemistry , Nonoxynol/pharmacokinetics , Nonoxynol/pharmacology , Polymethacrylic Acids/chemistry , Polymethacrylic Acids/pharmacokinetics , Polymethacrylic Acids/pharmacology
Due to the additional particle coalescence in the coating, changes in the dissolution profile occur over time in the formulations coated by aqueous ethylcellulose latex. Dry thermal treatment (DT) of the coating can be used as a prevention of this process. Alternatively, it is advisable to take advantage of the synergistic effect of high humidity during wet treatment (WT), which substantially accelerates the film formation. This can be a problem for time-controlled systems, which are based on the coating rupture due to the penetration of water into the core causing the increase in the system volume. This process can begin already during the WT, which may affect the coating adversely. The submitted work was focused on the stability testing of two pellet core compositions: pellets containing swelling superdisintegrant sodium carboxymethyl starch (CMS) and pellets containing osmotically active polyethylene glycol (PEG). Another objective was to identify the treatment/storage condition effects on the pellet dissolution profiles. These pellets are intended to prevent hypoglycemia for patients with diabetes mellitus and therefore, besides the excipients, pellet cores contain 75% or 80% of glucose. The pellet coating is formed by ethylcellulose-based latex, which provides the required lag time (120-360â¯min). The sample stability was evaluated depending on the pellet core composition (PEG, CMS) for two types of final pellet coating treatment (DT or WT). Scanning electron microscopy and Raman microspectroscopy revealed the penetration of glucose and polyethylene glycol from the core to the PEG pellet surface after WT. For the CMS sample, significant pellet swelling after WT (under the conditions of elevated humidity) was statistically confirmed by the means of stereomicroscopic data evaluation. Therefore, the acceleration of dissolution rate during the stress tests is caused by the soluble substance penetration through the coating in the case of PEG pellets or by dosage form volume increase in the case of CMS pellets. The observed mechanisms can be generally anticipated during the stability testing of the ethylcellulose coated dosage forms. The aforementioned processes do not occur after DT and the pellets are stable in the environment without increased humidity.
Cellulose/analogs & derivatives , Drug Compounding/methods , Drug Implants/chemistry , Glucose/chemistry , Polyethylene Glycols/chemistry , Starch/analogs & derivatives , Cellulose/chemistry , Chemistry, Pharmaceutical , Delayed-Action Preparations , Drug Liberation , Drug Stability , Excipients/chemistry , Glucose/pharmacology , Hot Temperature , Hypoglycemia/prevention & control , Particle Size , Solubility , Starch/chemistry , Surface Properties
