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This study aimed to create, develop, and optimize a biodegradable stent made of poly lactic co glycolic acid (PLGA) that contained clopidogrel and atorvastatin for the management of asthma. Solvent casting was used to create biodegradable stents. In particular, PLGA 75:25 polymer films were used to create stents using the solution-casting method. The base material was created by dissolving the polymer in isopropyl alcohol and adding PEG 400 as a plasticizer. As the active pharmaceutical ingredients in the stents, clopidogrel and atorvastatin were used. To avoid air bubbles, the resulting mixture was homogenized before being poured onto metal pans and allowed to gently evaporate in a refrigerator. The polymer films were then cut into strips, wound around cylindrical rods to form helical stents, and baked in an oven to guarantee that all of the isopropyl alcohol had evaporated. The biodegradable polylactic acid stents that included clopidogrel and atorvastatin demonstrated an impressive 99.34±0.44% encapsulation efficiency. Differential scanning calorimetry (DSC) analysis revealed that there were no chemical interactions between the stent's component parts. Significant water absorption over 80% was seen over a period of 8 days, which is remarkable. A thorough effect on disrupting plaque was seen at day 21, and on day 22, the stent began to biodegrade. Over the course of 20 days, the cumulative medication release percentage rose to 99.92%. According to the study's findings, treating atherosclerosis with an optimized biodegradable polymeric stent made of PLGA and combining atorvastatin and clopidogrel is a novel and promising treatment option.
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Objective: The study aimed to develop a polymeric nanosponge-based hydrogel system for enhanced topical application of fluconazole, an antifungal drug.Methods: Nanosponges were formulated using the emulsion solvent diffusion method using various polymers like hydroxypropyl methylcellulose, ethylcellulose and Eudragit RS 100. Polyvinyl alcohol and ethanol were used to prepare the aqueous and dispersed phases. Nanosponges were dispersed in an appropriate amount of gelling agent Carbopol 940 to get nanosponge gel. Drug–polymer interaction has been carried out by FTIR spectroscopy. The prepared nanosponges were evaluated for various tests like production yield, drug entrapment efficiency, compatibility and SEM studies. The nanosponge hydrogel was tested for pH, drug content, spreadability, in vitro diffusion and kinetic studies.Results: The drug entrapment efficiency of fluconazole nanosponges was found in the range of 52.3±0.84% to 80.8±0.36% for all formulations, respectively. The spreadability of prepared nanosponges gel formulation was in the range between 5.20±0.19 to 7.187±0.85.Particle size analysis showed that the average particle size of fluconazole nanosponges formulated using ethyl cellulose (F5) was found to be 334 nm. The zeta potential was found to be-10.4 mV, indicating the formulated fluconazole nanosponges (F5) had moderate stability. FTIR and DSC studies of pure drug and nanosponges suggested that the formulations were stable and there was no chemical interaction with polymer and other excipients. The optimised fluconazole topical nanosponge hydrogel (FG5) released 90.90% drug in 8 h.Conclusion: Fluconazole topical nanosponge hydrogel could be successfully prepared by emulsion solvent diffusion method. Fluconazole topical nanosponge hydrogel showed promising results under in vitro condition and thus, there exists a scope for evaluation of the developed nanosponge hydrogel for further pharmacokinetic studies, using appropriate test models.
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The pharmaceutical sector is looking for new ways to deliver drugs, and one such way is through thin films. It has been said that thin films offer an alternative to traditional dosage forms. They offer rapid, local, or systemic effects and are a very flexible platform. Furthermore, patients with dysphagia, elderly, paediatrics, or bedridden patients, as well as those who have difficulty accessing water, can easily utilize these systems on their own. There are several ways to administer these drug delivery systems, including transdermally, ocularly, buccally, sublingually, and orally.One of the most creative and patient-focused novel drug delivery systems is Orodispersible Thin Films (OTF). Numerous pharmaceutical companies and academic experts worldwide are currently investigating the potential of these films for delivering drugs derived from both synthetic and natural sources. The beauty of this special drug delivery method is that, as we can see from the subjects' consumption of conventional dosage forms (tablets, capsules), they don't require water to be consumed. Furthermore, these delivery methods do a great job of encouraging patient compliance in general, especially in the case of both older and pediatric patients.This review shows a detailed review of oral thin film its applications and method of preparation; mainly focus of this research is thin film introduction to researchers and last 10 y of research on thin film with drugs and polymers used in research.
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Objective To prepare silymarin phospholipids complex(SM-PC) and investigate its physicochemical properties. Methods On the basis of single-factor tests, the drug-lipid ratio, drug concentration and reaction temperature were selected as the factors of the central composite design and response surface methodology in the preparation of SM-PC by solvent volatilization, and the best process was optimized with the compound rate as the index. And its in vitro dissolution was measured. Results The optimum preparation technology of SM-PC was as follows: acetone was used as compound solvent, the concentration of SM was 8.0 mg/ml, the mass ratio of SM to phospholipid was 1∶1.8, the reaction temperature was 56 ℃ and the recombination rate was(95.15±1.55)% with deviation of less than 3%. The in vitro dissolution test showed that the dissolution of SM-PC was close to 90% in 60 min. The dissolution behavior of main component of silybin was similar to that of silymarin capsules(Legalon ®), which was higher than SM-API. Conclusion SM-PC was successfully prepared by central composite design response surface method, which significantly improved the dissolution and laid a foundation for the study of subsequent preparations.
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OBJECTIVE To standardize the use of sterile powder for injection redissolution solvent and intravenous drugs diluent solvent, and ensure the safety of clinical drug use. METHODS The intravenous drug resolvent generation system and the intravenous drug solvent incompatibility rules library were constructed and operated by prescription-checking pharmacist team in our hospital by formulating a list of intravenous drugs needed to be dissolved with sterilized water for injection and a contraindication list of intravenous solvent compatibility. The unreasonable medical orders reviewed and intervened in our hospital from January to April 2023 (before the implementation of the intravenous drug solvent incompatibility rules library) and from May to August 2023 (after the implementation) were analyzed statistically to compare the number of unreasonable solvent selection orders, interception rate, and the success rate of pharmacists’ interventions for unreasonable solvent selection orders before and after the implementation. RESULTS Before the implementation of the solvent incompatibility rules library, a total of 5 229 groups of medical orders with unreasonable solvent selection in our hospital were identified, among which there were 1 204 groups of seriously unreasonable medical orders, with interception rate of 23.03% and the success rate of pharmacists’ intervention of 15.90%. After the implementation of the solvent incompatibility rules library, the total number of medical orders with unreasonable solvent selection was 3 258 groups, among which there were 1 148 groups of seriously unreasonable medical orders, with interception rate of 35.24% and success rate of pharmacists’ intervention of 24.83%, being significantly higher than before implementation (P<0.01 or P<0.001). CONCLUSIONS The establishment and application of the intravenous drug resolvent generation system and the solvent incompatibility rules library can significantly increase the interception rate of unreasonable solvent selection orders and the success rate of pharmacists’ interventions, and ensure the safety of clinical drug use.
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Fluvastatin sodium is a hypolipidemic agent that reduces cholesterol synthesis by inhibiting HMG-CoA reductase. The drug has a comparatively short biological half-life (1.2 hours) and low bioavailability (24–29%), making it an appropriate candidate for a sustained-release drug delivery system. This study aimed to formulate biodegradable microspheres of fluvastatin sodium by optimization through an experimental design approach. Microspheres containing fluvastatin sodium were prepared by o/w emulsification solvent evaporation method using poly (lactic-co-glycolic acid) (PLGA 50:50) as a biodegradable polymer. 32 full factorial design was applied to study the effect of drug to polymer ratio and stirring speed on dependent variables, i.e. particle size, entrapment efficiency, Q1h, t80%. Prepared formulations were subjected to evaluate physicochemical properties and release characteristics. DSC and FTIR proved no interaction between the drug and excipients. Microspheres possessed size in the range of 193 to 344 ?m and entrapment efficiency varied from 63.1 to 85.6%. Formulations showed drug release up to 23% within 1-hour. while t80% was found in between 3–9 hours. Regression analysis and ANOVA results suggested a significant effect (p<0.05) of variables on responses. The results of the present study suggested that biodegradable microspheres of fluvastatin sodium prepared using poly (lactic-co-glycolic acid) can be a promising alternative for conventional delivery and suitable for sustained drug release.
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The formulation of atenolol-loaded microballoons involved the use of Eudragit RS 100, HPMC K4 M as a polymer, and span 80 as a surfactant. The microballoons were prepared by an emulsion solvent diffusion (non-aqueous) using liquid paraffin, methanol, and dichloromethane as a processing medium. The Box-Behnken design was utilized to get optimized formulation using a concentration of HPMC K4 M (A), Concentration of Eudragit RS 100 (B), Concentration of surfactant (C), and stirring speed (D) as an independent parameter while, Particle size (Y1), entrapment efficiency (Y2) and %buoyancy (Y3) using as a dependent parameter. For the optimised formulation, the mean particle size was 85.878 ± 1.063 ?m, entrapment efficiency was 92.26 ± 1.65%, and buoyancy was 89.19 ± 1.48% found. An image of the formulation taken using a scanning electron microscope (SEM) reveals discrete particles with a smooth surface texture, a hollow interior, a spherical shape, and a particle size of less than 200 ?m. The FTIR study confirms there was no interaction between the drug and excipients. The in-vitro drug release study found that atenolol-loaded microballoons released the drug for up to 12 hours as compared to the pure drug. This was due to increasing the gastric residence time and absorption area in the stomach. The drug release kinetic study reveals that it follows the Higuchi model and the drug release mechanism was type II transport which was obtained from the Korsmeyer Peppas model. The stability study shows that there is no significant change in the optimized microballoons for 30 days as per ICH guidelines.
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Curcumin is widely known for its antibacterial, antioxidant and anti inflammatory effects and has been reported to possess anticancerous activity as well. However, its medical application is limited because of poor bioavailability and rapid metabolism. In this study, we encapsulated curcumin in solid lipid nanoparticles and studied its anticancerous effect in Dalton’s Ascites Lymphoma (DAL) mice model. The physicochemical characteristics of curcumin solid lipid nanoparticles (CUR-SLN) were assessed and the anticancer efficacy was determined by in vivo studies. The curcumin solid lipid nanoparticles were synthesized by solvent emulsification evaporation method with particle size less than 100 nm. Antitumor effect of nanocurcumin (50 mg/kg) and curcumin (100 mg/kg) was evaluated in Dalton’s Ascites Lymphoma bearing mice. Pathological and immunohistochemical parameters were studied. Mean survival time and percentage increase in lifespan were assessed. Nanocurcumin group showed more significant influence in reducing tumor volume and weight, inducing apoptosis, reducing angiogenesis and invasion restoring antioxidant parameters and increased mean survival time. Curcumin and nanocurcumin inhibited the activation of nuclear factor-kappa B (Nf-kB), and thereby proved the pathway by which it induced anti-angiogenic and anti-invasive property.
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Objective To establish a solvent desorption inductively coupled plasma-mass spectrometry (ICP-MS) method for determination of iodine in workplace air. Methods Iodine in workplace air was collected with alkaline activated carbon tube and desorbed with 10.0 mL pure water or 20 mmol/L sodium bicarbonate solution. Rhenium-185 was used as an internal standard for quantification. The sample was determined in standard mode and kinetic energy discrimination collision (KED) mode by ICP-MS. Results In standard mode, iodine showed a good linear range in the concentration of 9.0 to 1 100.0 μg/L, with a correlation coefficient of 0.999 3 and a detection limit of 2.7 μg/L. In KED mode, iodine showed a good linear range in the concentration of 24.3 to 800.0 μg/L, with a correlation coefficient of 0.999 1 and a detection limit of 7.3 μg/L. The average desorption efficiency using pure water ranged from 99.1% to 106.7%, with within-run relative standard deviation (RSD) of 3.1% to 8.0% and between-run RSD of 4.9% to 9.3%. The average desorption efficiency using sodium bicarbonate solution ranged from 96.5% to 105.3%, with within-run RSD of 4.9% to 8.6% and between-run RSD of 2.5% to 9.9%. There were no statistical significant differences in the main effects of desorption solution, ICP-MS detection mode, their interaction on average desorption efficiency and within-run RSD (all P>0.05). Samples could be stored at room temperature for at least 7 days. Conclusion This method is highly sensitive, accurate, and suitable for the determination of iodine in workplace air. The sample pretreatment is simple and rapid.
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This study aimed to prepare silk fibroin nanoparticles (SF-NPs) and assess the physicochemical properties and biocompatibility of the formulation. An optimized and simplified solvent displacement method was employed to obtain SF-NPs. Single-factor prescription screening, such as silk fibroin (SF) solution concentration, the ratio of SF solution to organic solvent, ultrasonication power and time, and different types of organic phases, was used to optimize the formulation. The characterization of the optimal formulation included particle size, polydispersity index (PDI), zeta potential, morphology, and stability. The in vitro cell compatibility of the nanoparticles was evaluated using CCK-8 and Calcein-AM/PI cell viability staining. The results showed that when SF concentration was 20 mg·mL-1, volume ratio of aqueous phase to acetone was 1∶6, ultrasonic power was 80 W and ultrasonic time was 3 min, the best SF-NPs was obtained. The nanoparticles prepared in this study exhibit a near-spherical shape, with a uniform size distribution, having an average size of 144.8 nm, a PDI of 0.174, and a zeta potential of -27.35 mV. Results from in vitro cell experiments demonstrate excellent cell compatibility of SF-NPs, showing the ability to promote cell proliferation. The SF-NPs which were successfully prepared in this study exhibit uniform particle size and excellent biocompatibility.
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Objective: To develop asolvent extraction-direct mercury analyzer method for determination of methylmercury in urine. Methods: After the urinehydrolyzesd by hydrobromic acid, methylmercury was extracted by tolueneand reverse-extracted from L-cysteine solution, it was then detectedbydirect mercuryanalyzer. Results: The linear range was 0.2-50.0 μg/L, and the related coefficient was 0.9999. The relative standard deviations (RSD) within the group were 5.04%-6.64%, and the RSD between the group were 5.65%-8.11 %. The average recovery efficiencies were 85.4%-95.5%. The detection limitation was 0.0482 μg/L and the quantification concentrations was 0.1607 μg/L. Conclusion: The method, which has low detection limit, high sensitivity, easy to operate, is stability for the determination of methylmercury in urine.
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Mercúrio , Compostos de MetilmercúrioRESUMO
ObjectiveTo investigate the effect of microemulsion on the distribution of index components in different phases of Zexietang extract based on high performance liquid chromatography(HPLC) and phase separation process. MethodParticle size meter and transmission electron microscope were used to characterize the colloidal particles in blank microemulsion, aqueous extract of Zexietang and microemulsion extract of Zexietang. The phase separation process was established by high-speed centrifugation and dialysis, and based on this process, the aqueous extract and microemulsion extract of Zexietang were separated into the true solution phase, the colloidal phase and the precipitation phase, respectively. The contents of six components, including atractylenolide Ⅲ, atractylenolide Ⅱ, 23-acetyl alisol C, alisol A, alisol B and alisol B 23-acetate, were determined by HPLC with the mobile phase of water(A)-acetonitrile(B) for gradient elution(0-5 min, 40%-43%B; 5-20 min, 43%-45%B; 20-45 min. 45%-60%B; 45-75 min, 60%-80%B). The solubility of the index components in water and microemulsion was determined by saturation solubility method. ResultThe colloidal particles in the aqueous extract, microemulsion extract and blank microemulsion were all spherical, and the particle size, polydispersity index(PDI) and Zeta potential of the colloidal particles were in the order of aqueous extract >microemulsion extract >blank microemulsion. The results of phase separation showed that the colloidal phase and the true solution phase could be completely separated by dialysis for 2.5 h, and the phase separation process was tested to be stable and feasible. Compared with the aqueous extract of Zexietang, the use of microemulsion as an extraction solvent could increase the contents of atractylenolide Ⅲ, 23-acetyl alisol C, atractylenolide Ⅱ , alisol A, alisol B and alisol B 23-acetate by 3.75, 6.82, 35.47, 10.66, 35.41, 27.75-fold, and could increase the extraction efficiencies of the latter five constituents by 2.03, 1.15, 1.70, 6.43, 5.53 times. The solubility test showed that the microemulsion could significantly improve the solubility of atractylenolide Ⅱ, alisol A, alisol B and alisol B 23-acetate, but it had less effect on the solubility of atractylenolide Ⅲ and 23-acetyl alisol C. ConclusionMicroemulsion can improve the extraction efficiency and increase the distribution of the index components in the colloidal phase state of Zexietang to different degrees, providing a reference for the feasibility of microemulsion as an extraction solvent for traditional Chinese medicine.
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Alkaloids, widespread in plants, have a series of pharmacological activities and have been widely used to treat various diseases. Because alkaloids are usually presented in multicomponent mixtures and are deeply low in content, they are very difficult to extract and separate by traditional methods. High-speed counter current chromatography(HSCCC) is a kind of liquid-liquid chromatography without solid support phase, which has the advantages of large injection volume, low cost, and no irreversible adsorption. Compared with the traditional methods of extraction and separation of alkaloids, HSCCC can ensure the separation of many different alkaloids at one time, with a high recovery and large amount. In this paper, the advantages and disadvantages of HSCCC compared with traditional separation methods were discussed and the solvent system and elution mode of HSCCC used to separate alkaloids in recent years were summarized by referring to the relevant literature to provide some references for the separation of alkaloids by HSCCC.
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Produtos Biológicos , Distribuição Contracorrente/métodos , Cromatografia Líquida de Alta Pressão/métodos , Alcaloides/análise , Solventes/químicaRESUMO
Improved analytical methods for the metabolomic profiling of tissue samples are constantly needed.Currently,conventional sample preparation methods often involve tissue biopsy and/or homogenization,which disrupts the endogenous metabolome.In this study,solid-phase microextraction(SPME)fibers were used to monitor changes in endogenous compounds in homogenized and intact ovine lung tissue.Following SPME,a Biocrates AbsoluteIDQ assay was applied to make a downstream targeted metab-olomics analysis and confirm the advantages of in vivo SPME metabolomics.The AbsoluteIDQ kit enabled the targeted analysis of over 100 metabolites via solid-liquid extraction and SPME.Statistical analysis revealed significant differences between conventional liquid extractions from homogenized tissue and SPME results for both homogenized and intact tissue samples.In addition,principal component analysis revealed separated clustering among all the three sample groups,indicating changes in the metabolome due to tissue homogenization and the chosen sample preparation method.Furthermore,clear differences in free metabolites were observed when extractions were performed on the intact and homogenized tissue using identical SPME procedures.Specifically,a direct comparison showed that 47 statistically distinct metabolites were detected between the homogenized and intact lung tissue samples(P<0.05)using mixed-mode SPME fibers.These changes were probably due to the disruptive homogenization of the tissue.This study's findings highlight both the importance of sample preparation in tissue-based metabolomics studies and SPME's unique ability to perform minimally invasive extractions without tissue biopsy or homogenization while providing broad metabolite coverage.
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Objective: To establish a solvent desorption-gas chromatography method for determination of dimethyl carbonate (DMC) in workplace air. Methods: The air samples were collected using activated carbon tubes, desorbed by carbon disulfide, separated by dimethylpolysiloxane capillary columns, and detected by a flame ionization detector. Results: The linear range of DMC was 2.14 to 1.07×104 mg/L, and the correlation coefficient was greater than 0.999. The detection limit was 0.14 mg/L, the lower limit of quantification was 0.47 mg/L, the minimum detection concentration was 0.10 mg/m3, and the minimum quantification concentration was 0.32 mg/m3 (based on 1.5 L workplace air). The average desorption efficiency of the method was 96.2% to 102.0%. Both the within-run and between-run relative standard deviations were 0.9% to 2.3%. The samples could be stored for at least seven days at four celsius degree. Conclusion: This method shows high desorption efficiency, high sensitivity, good precision and is simple in using. It can be used for the determination of DMC in workplace air.
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Objective: To establish a solvent desorption-gas chromatography method for the determination of 1,1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane in workplace air. Methods: The 1,1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane in workplace air were collected using activated carbon tubes, desorbed with carbon disulfide, and separated and detected by gas chromatography. The quantifications were based on standard curves. Results: The linear ranges of 1,1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane were 0.98-395.50 and 0.87-395.50 mg/L, respectively, with the correlation coefficient of 0.999 95. The detection limits were 0.29 and 0.26 mg/L, respectively. The average of desorption efficiency was 92.04%-104.67%. The within- and between-run relative standard deviations were 1.42%-2.09% and 1.63%-6.09%, respectively. The sampling efficiency was more than 98.00%. The samples could be stored at room temperature for at least 14 days. Conclusion: This method can be used in detection of 1,1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane in workplace air.
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@#Paint contains various complex chemical mixtures, such as aliphatic hydrocarbons, aromatic hydrocarbons (primarily toluene), ketones, and benzene as reported at previous studies. Toxicity from some chemicals can cause early DNA damage with various factors. A scoping review was conducted via literature review on relevant studies on the effect of paint exposure on paint workers and DNA damage. A systematic search was conducted in October 2021 via PubMed, Scopus, and Web of Science databases. The key terms used were paint, solvent-based paint, organic solvent, mixed organic solvent, occupational exposure and DNA damage, oxidative stress, genotoxicity on a painter, paint worker. From 561 articles, only 13 articles were finally selected based on the inclusion, exclusion criteria, and eligibility criteria. The literature showed that biomonitoring studies on painters were consistently reporting positive and significant DNA damage due to exposure to different types of compounds mixed in a paint. However, there were fewer studies on paint manufacturing factory workers compared to painters while paint manufacturing workers exposed various chemical everyday during the paint production which potentially susceptible to occupational toxicity. In conclusion, this review suggests that exposure to paints could induce early DNA damage among paint workers and further investigations on paint exposure among paint manufacturing factory workers and the DNA damage were needed in order to improve occupational health among paint workers in the future.
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@#Oral route drug delivery system is still considered as the most convenient and patient friendly drug delivery route. Over the decades, many research has been performed to improve the functionality oral dosage form. Orally disintegrating film (ODF) is a newer oral drug delivery system, which is in the form of a thin film that will disintegrate in the oral cavity within a matter of seconds. The aim of this review paper is to recap ODF, its benefits, formulation contents and manufacturing method. With more research and development work has been conducted on ODF, the dosage form is expected to be manufactured and scaled up to be commercializable products to be sold in the market.
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A flavoring agent and a suspension agent were prepared for extemporaneous compounding. The stability of the two agents before and after drug loading was investigated, and the taste of the suspension after extemporaneous compounding was evaluated by electronic tongue technology. The two agents remained stable under the conditions of influence factor test, accelerated test and long-term test. The appearance properties of the two agents did not change. The relative density of the flavoring agent was maintained at 1.053-1.075, and the pH was stable at 4.2-4.5. The relative density of the suspension agent was maintained at 0.999-1.022, and the pH was stable at 4.0-4.5. Seven kinds of drugs, including warfarin sodium tablets and spironolactone tablets, were mixed with these two oral solvents, and the content uniformity and stability were detected respectively. The results showed that the preparations could be evenly dispersed and the physical and chemical properties were stable. The results of taste evaluation showed that in captopril group and chloral hydrate group, the flavoring agent had the best effect on taste correction. In warfarin sodium group, rifampicin group, spironolactone group, vitamin B1 group and vitamin B2 group, the blending agents had the best effect on taste correction.
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Azithromycin dry suspension is one of the most commonly used drugs in pediatric clinic, but its taste masking has been difficult to achieve. 5 representative products of azithromycin dry suspension were chose to compare their tastes both using electronic tongue and human sensory evaluation methods, and there existed the differences of bitterness, later bitterness, graininess, and adhesion among these products. Raman micro-imaging was used to determine the difference in taste mainly due to different prescription ingredients and manufacturing techniques. Through mixing the dry suspensions with alkaline mixing solvent, the bad taste of each product was masked after evenly dispersing in the solvent, and their tastes were all close to the taste of the solvent. In the future, it is planned to investigate the stability and bioavailability of the solvent preparations, and then to give the medication suggestion of solvent preparation after ensuring their efficacy.