ABSTRACT
@#With the rapid advancement of science and technology, the application of 3D printing technology for personalized drug manufacturing is becoming increasingly sophisticated.Compared to traditional manufacturing technology, 3D printing can easily customize preparations with specific sizes, shapes and release behaviors for personalized drug use.This review summarizes the principles of several 3D printing technologies commonly used in drug manufacturing, lists the unique advantages and application examples of 3D printing technology for pharmaceutical preparation, analyses the current research status and development trends of the global industry of drug 3D printing, and summarizes the current problems and challenges facing drug 3D printing, aiming to provide some guidance for researchers of 3D printed drugs.
ABSTRACT
As a natural drug delivery carrier with rough and porous surface and hollow core， yeast microcapsules have good safety， high targeting and high stability， and have excellent application prospects in oral drug delivery systems. Yeast cells can be treated and washed with acid-base and organic solvents to obtain loose and porous yeast microcapsules. Yeast microcapsules can encapsulate drugs through electrostatic interactions， passive diffusion， hydrophobic interaction and other methods. The surface of yeast microcapsules is mainly composed of β-glucan， which can maintain stability in the gastrointestinal environment； it can be recognized by the surface-related receptors of immune cells， thus activating the immune response， and can be transported to the lesion site with the movement of lymphocytes after being ingested. Yeast microcapsules are safe and very suitable for delivering vaccines， anti-inflammatory drugs， and anti-tumor drugs. They can not only achieve oral delivery of the aforementioned drugs， but also enhance drug efficacy and improve drug targeting. In the future， more research on systemic transport mechanisms or the development of more efficient combination drug delivery systems can be carried out to fully exhibit the clinical value of yeast microcapsules.
ABSTRACT
@#Most drugs taste bitter and irritating, resulting in poor compliance of patients, and the bad odor affects the therapeutic effect. The successful research and development of a drug should not only conform to the five quality characteristics of effectiveness, stability, safety, uniformity and economy, but also the compliance of patients to drugs with bad odor. The development of taste masking techniques is critical for bitter drugs.This review describes the principles, advantages and drawbacks of traditional taste masking techniques, and introduces the mechanism and application of novel taste masking techniques, such as melt granulation, hot melt extrusion, 3D printing, drug complex preparation, and bitter taste inhibitors. The in vitro evaluation methods of drug taste masking effect, such as functional magnetic resonance imaging, in vitro dissolution, and electronic tongue technology, are described. And introduce in vivo evaluation methods, such as animal and human taste, in the field of taste masking effect. A new strategy of BP neural network prediction model for drug taste evaluation is proposed, with a view to providing theoretical reference for the future research on drug taste masking.
ABSTRACT
@#In this study, the formulation and preparation process of curcumin nanocrystalline injection were optimized to improve curcumin dissolution rate and bioavailability in vivo.Media grinding method was used to prepare curcumin nanocrystals, and the particle size was used as the evaluation index.The Box-Behnken experimental design was used to optimize its formulation and preparation process, and to characterize its physical and chemical properties.In addition, the dissolution of nanocrystal with different particle sizes was investigated by the paddle method, and the pharmacokinetics in rats were studied.The experimental results showed that the optimal formula and process were obtained through Box-Behnken experimental design, and that uniform curcumin nanocrystals with an average particle size of 223.1 nm were obtained.The results of X-ray diffraction and differential scanning calorimetry analysis showed that the crystal form was stable during the preparation of nanocrystals. In vitro dissolution experiments with different particle sizes showed that the dissolution rate and the degree of dissolution would increase if the particle size was smaller.Pharmacokinetic studies in rats showed that cmax and AUC0-∞ of curcumin nanocrystal injection were 4.9 and 4.1 times that of curcumin raw materials, respectively.In summary, the curcumin nanocrystal injection developed in this research have a stable preparation process and can significantly improve the dissolution rate and bioavailability of the drug, which provides some ideas for the research on curcumin preparation.
ABSTRACT
@#Respiratory mucosal immune system is the body''s first line of defense against infection.Since the outbreak of novel coronavirus disease 2019 (COVID-19) in 2019,nasal mucosal immune vaccine, with its ability to induce cellular, humoral and mucosal triple immune responses, has become a research hotspot.This article focuses on novel coronavirus, with an understanding of its structure and pathogenesis, a brief introduction to the immune mechanism of nasal mucosa, a summary of the different types of nasal mucosal immune vaccines and their clinical research, aiming to provide some theoretical reference for the development of new vaccines, and exploration of the best methods and strategies to combat COVID-19.
ABSTRACT
Objective To establish a high performance liquid chromatography(HPLC)method for the determination of disodi-um edetate(EDTA-2Na)in nalmefene hydrochloride injection. Methods Content of EDTA-2Na in nalmefene hydrochloride injection was determined by HPLC. C18 Column was used. The mobile phase consisted of 0.3%tetrabutylammonium hydroxide solution-water-acetonitrile(20:45:35)with a flow rate of 1.0 ml/min,and the detection wavelength was 254 nm. The column temperature was 30℃and the injection volume was 20μl. Results The quantification limit and detection limit were 0.199 and 0.060μg/ml,respectively;the linear equation for the disodium edetate was Y=10.125X-0.216,and the calibration curves were linear within the range of 2.4593~7.3780 μg/ml(r=1.000). Each concentration of the average recovery was between 98~102%(n=9)(RSD%=0.58%). Conclusion The method can be used for the determination of EDTA-2Na in nalmefene hydrochloride injection,which is convenient,fast,sensitive and reproducible,with good precision,specificity and accuracy.
ABSTRACT
Objective To compare the release rate and bioavailability of progesterone injection with different particle sizes. Methods The preparation of progesterone nano sized injection and micron sized injection were performed by power X-ray diffraction (PXRD)and Fourier trensform infrared spectooscory(FTIR). The dissolution rate of two preparations and progesterone was compared by dialysis Method. HPLC-MS method was used to determine the progesterone concentration of plasma in rats after intramuscular injec-tion of different preparations,and the main pharmacokinetic parameters were calculated and analyzed statistically. Results Based on the analysis of PXRD and FTIR,there were no crystal structure changes between the two preparations and progesterone. The complete release of progesterone nano sized injection and micron sized injection required 2 and 4 h in the PBS solution,respectively,while the release of progesterone required nearly 40 h. In the pharmacokinetic experiment,compared with progesterone injection,the Cmax of pro-gesterone nano sized injection and micron sized injection were increased by 1.8 and 1.7 times,respectively;the AUC0-t were increased by 2.95 and 1.63 times,respectively. The bioavailability of both was higher than that of progesterone injection. Conclusion The re-lease rate bioavailability of progesterone nano sized injection and micron sized injection is higher than that of progesterone and proges-terone injection. Bioavailability of progesterone nano sized injection is higher than that of progesterone micron sized injection.
ABSTRACT
Objective To prepare naloxone hydrochloride nasal spray and evaluate the ciliotoxicity and pharmacokinetics of the formulation. Methods The stability of naloxone hydrochloride was studied in pH3.5-5.5. Penetration promoting effects of absorp-tion enhancers on the naloxone hydrochloride were evaluated. Nasal ciliotoxicity studies were carried out using isolated toad palate. Rats were treated with naloxone hydrochloride solution by intramuscular injection of nasal drops to evaluate the pharmacokinetics. Results Naloxone hydrochloride solution was stable in pH3.5-5.5. Disodium ethylenediaminetetraacetic acid(0.2%,W/V)had the best penetration promoting effect on naloxone hydrochloride. Naloxone hydrochloride nasal spray did not exhibit obvious nasal ciliotox-icity compared to the negative control. The nasal spray had a faster therapeutic effect and its bioavailability was similar to that of the in-tramuscular injection. Conclusion Naloxone hydrochloride nasal spray prepared in this research is stable with no obvious nasal cilio-toxicity,has faster therapeutic effect,and good bioavailability,so may have a broad application prospect.
ABSTRACT
New registry classifications of chemical drugs redefined the concepts of new drugs and generic drugs. New drugs emphasize the international innovation including innovate new drugs and modified new drugs. Modified new drugs are improvement of drugs already on the market to achieve superior efficacy. With the advantages of high success rate,high return,low risk and long life cycle,modified new drugs have become the mainstream of new drugs research and development in the world. Modified new drugs R&D in China should be based on clinical demand and focused on the differentiation research in order to obtain new preparations with signif-icant clinical advantages to better serve the clinical practise. This paper states the concept and characteristics of modified new drugs in China,makes case analysis and shares the development history of blockbuster modified new drugs in the world,clarifies the opportuni-ties and challenges and provides ideas for the future development of modified new drugs in China.
ABSTRACT
Objective To establish a high performance liquid chromatography(HPLC)method for determining the content and dissolution of soluble guanylate cyclase(sGC)-003 tablets. Methods Content and dissolution of sGC-003 tablets were deter?mined by HPLC. Phenomenex Luna C18 column(250 mm×4.6 mm,5μm)was used. The mobile phase was acetonitrile-water(40∶60,V/V), with a flow rate of 1.0 ml/min,and the detection wavelength was set at 214 nm. The column temperature was 40℃and the injection volume was 20μl(injection volume of dissolution was 80μl). Dissolution of sGC-003 tablets was determined by the second method described in Chinese Pharmacopoeia(ChP)2015. 900 ml of pH 4.5 acetic acid buffer,pH 6.8 phosphoric acid buffer and water were used as dissolution media at the rotation speeds of 50 and 75 r/min to select the dissolution condition. Results This method had high specificity. The average recovery was about 99.58%(RSD=0.75%,n=9). And the working solution was stable within 12 h. The calibra?tion curves were had good linearity(R2=1)within the concentration range of 0.25-50μg/ml. The method of dissolution tests for sGC-003 tablets was established that 900 ml pH 6.8 phosphoric acid buffer was used as dissolution medium and paddle rotation speed was 50 r/min. The dissolution would be 80%at 30 min. Conclusion The dissolution condition can be used to determine the dissolution of sGC-003 tablets. The HPLC method is convenient,fast,sensitive and accurate in determining the content and dissolution of sGC-003 tablets.
ABSTRACT
Objective To determin the dissolution of testosterone undecanoate capsule in vitro with an established HPLC method. Methods The dissolution was determined by the second method described in China(ChP)2015,Pharmacopoeia. Totally 900 ml of 0.25%sodium lauryl sulfate solution with pH 6.8 phosphate buffer were used as dissolution media,and the rotation speed was 75 r/min. The dissolution time was 120 min and the dissolution was determined by HPLC. The HPLC column was phenomenex@C18 column(250 mm×4.6 mm,5μm). The mobile phase was 2-propanol-acetonitrile-water(45∶45∶10,V/V/V)with a flow rate of 1.0 ml/min and the detection wavelength of 240 nm. The column temperature was 40℃and the injection volume was 20μl. Results The average recovery of the method was about 100.55%(n=9). The calibration curves showed good linearity(r2=0.9999,n=7)within ranges of 1-50μg/ml. Conclusion The method is convenient and sensitive in the dissolution determination of testosterone undecanoate capsule.
ABSTRACT
Objective To develop a HPLC method for determining the dissolution of desogestrel and ethinylestradiol tablets. Methods The dissolution was determined by the second method described in Chinese Pharmacopoeia(ChP)2015. In total 500 ml of 0.05%sodium lauryl sulfate solution was used as dissolution media,and the rotation speed was 50 r/min. The dissolution time was 30 min and the dissolution was determined by HPLC. The HPLC column was Agilent SB C18 column(150 mm×4.6 mm,5μm). The mobile phase:acetonitrile as mobile phase A,acetonitrile-water(50∶50,V/V)as mobile phase B with gradient elution. The flow rate was 1 ml/min. The detection wavelength of desogestrel and ethinylestradiol was 210 nm. The column temperature was 40℃and the injection volume was 100μl. Results The average recoveries were 99.68%for desogestrel and 99.40%for ethinylestrsdiol,and the stability of work?ing solutions was acceptable in 12 h. The calibration curves were linear within the range of(0.06-0.36)μg/ml(r=0.9999)for desoges?trel,(0.012-0.072)μg/ml(r=0.9999)for ethinylestradiol,respectively. Conclusion The method is convenient and precise in the dis?solution determination of desogestrel and ethinylestradiol tablets.
ABSTRACT
Objective To prepare paliperidone palmitate injection,establish the testing method for its release rate,and vali?date the methodology. Methods Wet grinding was used to prepare paliperidone palmitate injection,high performance liquid chroma?tography was adopted to establish release rate detection,and validate its methodology. Results The average particle diameter of home-made agent was about 1μm,and it was an irregular bulk observed under transmission electron microscope;the precision of es?tablished release rate detection was 1.5%,recovery rate was 100.70%and stability RSD was 0.33%. The average release rate in vitro of home-made agent in three batches was:8.00%in 1.5min,62.26%in 20 min,and 85.44%in 45 min. Conclusion The particle size distribution and release rate of prepared sustained-release injection are consistent with those of original research,and the testing method of release rate is simple,sensitive and accurate,which could effectively monitor the product quality. The average release rates of agent in three batches are within the scope of quality standards.
ABSTRACT
Objective To establishe an HPL C method to determine the dissolution of progesterone nanocrystal capsule. Methods The dissolution was determined by the first method described in Chinese pharmacopoeia (ChP) 2010. Totally 900 ml of 0.25% sodium lauryl sulfate solution were used as dissolution media, and the rotation speed was 75 r/min. The dissolution time was 45 min and the dissolution was determined by HPLC. The HPLC column was Agilent TC C18 column (150 mm×4.6 mm,5μm). The mobile phase was methanol-acetonitrile-water (35∶40∶25,V/V/V), with a flow rate of 1.0 ml/min and the detection wavelength of 241 nm. The column temperature was 25℃and the injection volume was 20 μl. Results The average recovery of the method was about 100.02%(n=15 ), and the stability of working solutions was acceptable in 24 h (RSD=0.92%,n=8). The calibration curves showed good linearity (r=1,n=6) within ranges of 2.78-66.7 μg/ml. Conclusion The method is convenient and sensitive in the dissolution determination of progesterone nanocrystal capsule.
ABSTRACT
OBJECTIVE To investigate the effect of ketoconazole on the pharmacokinetic (PK) behaviors of midazolam and its metabolite through intranasal and intragastric(ig) routes in rats. METHODS Twenty-four rats were evenly divided into 4 groups. Two groups of rats were administrated singly with midazolam (1 mg?kg-1) through intranasal or ig route. The other two groups were concomitant with CYP3A inhibitor,ketoconazole(30 mg?kg-1),midazolam(1 mg?kg-1)through the same two routes. Blood samples were collected from different time points. Plasma concentration of midazolam and 1′-hydroxymidazolam was determined. Major pharmacokinetic parameters were calculated and statistical tests were performed by using t test. RESULTS Tmax was about 2 and 25 min for rats administered singly with midazolam via intranasal or ig routes,respectively and AUC was 296 and 179 μg?L-1?h, respectively. When concomitant with ketoconazole,AUC increased to 2.1 and 3.3 folds the original value for intranasal and ig routes,respectively. However,the Tmax value of midazolam via intranasally didn′t change after being coadministrated with ketoconazole,but Tmax increased to 1.14 h via ig. CONCLUSION Compared with administration via ig,intranasal route administrated midazolam displays significant advantages of faster absorption and higher exposure,which are vital for the first aid. Concomitant with CYP3A inhibitor and midazolam via intranasal route,the absorption speed is not affected,but with the metabolism blocked,the systemic exposure is greatly elevated. While via ig,both absorption speed and metabolism are inhibited. The dose should be cut down or the dosing interval increased in clinic practice in this concomitant situation.
ABSTRACT
In a number of local wars and crisis in the region, the US military has shown the world its powerful military special drug development capabilities. To meet challenges including war wounds, chemical or biological weapons prevention , extreme environments as well as infectious diseases, the US military has developed a large number of military special needs medication. In this paper, in review of US medical product manuals and literature, we summarize the research progress in the US military drug prevention and treatment of chemical weapons injuries, drug prevention and treatment of infectious diseases, war injuries drugs, pharmaceutical and biological weapons and military operations medicament for the treatment of injury.
ABSTRACT
Objective To establish and optimize the rat jugular vein catheterization model in our lab, and perform a cross-over study using this model to compare the pharmacokinetic characters of a newly developed midazolam formulation to the existing preparation. Methods Six SD rats (half male and half female) received the right jugular vein catheterization when the rats were sufficiently anesthetized. One week after the operation, all the rats were used to conduct a cross-over double period pharmacokinetic study. Totally1.33 mg/kg midazolam solutions from automatic needle and clinic available injection were adminisered to the jugular vein catheterization rats via im route. The washout period was 5 days. Exact volume of blood samples at designed time points were taken through the catheter. After preparation, the concentrations of midazolam in rat plasma were determined by using established LC-MS/MS method. The corresponding pharmacokinetic parameters were calculated by WinNolin software. Results The rat jugular vein catheterization model was successfully built. Blood was easily sampled and rats were well tolerated, meeting the requirement of repeated blooding. This model solved the bottleneck of cross-over study performed in rats. The pharmacokinetic behavior of newly developed midazolam formulation had no difference with that of clinic injections. The relative bioavailability was around 99%. Conclusion Rat jugular vein catheterization model is proved to be that of a propagating technique to do the cross-over study and to evaluate the pharmacokinetic characters of novel formulations.
ABSTRACT
Objective To evaluate the anticonvulsant effect of midazolam and diazepam when administered nasally on maximal electroshock seizure and metrazol seizure threshold test models .Methods Rats were randomly divided into 7 groups:model group, low-dose, middle-dose and high-dose of midazolam nasal spray groups , diazepam nasal spray in low-dose, middle-dose and high-dose of midazolam nasal spray groups .After the establishment of the maximal electroshock seizure( MES) and metrazol seizure threshold test models ( MST) in rats, the anticonvulsant effects of different doses of midazolam and the clinically used antiepileptic drug diazepam were evaluated and compared .HE staining was used to observe the histopathological changes in the hippocampus , cortex and amygdala in rats .Results Significant anticonvulsant effects were observed on MES and MST in rats pretreated with different dosages of midazolam .In addition , the anticonvul-sant effects of midazolam were stronger than those of diazepam at the same dosage on MES and MST (P<0.05,P<0.01). Histopathological results showed that both midazolam and diazepam could effectively prevent the seizure -induced brain inju-ries, inhibit the increase of microglial cells and the inflammatory cell infiltration in the hippocampus, cortex and amygdala, and reduce the nucleus pycnosis and neuronophagia .Conclusion Midazolam has significantly anticonvulsant and neuropro-tective effects on different seizure models when administered nasally in rats .
ABSTRACT
Objective To establish an HPLC method for the determination of metoclopramide (MCP) and its related substances in MCP nasal spray .Methods Chromatographic separation was performed on an Agilent TC-C18 column (250 mm ×4.6 mm,5 μm) using acetonitrile and phosphate buffer solution (0.05 mol/L potassium dihydrogen phosphate solution, added with 5 ml of triethylamine and adjusted to pH 4.0 with phosphoric acid)(19∶81) as the mobile phase at 1.0 ml/min.The detection wavelength was 275 nm and the column temperature was set at 30℃.Results and Conclusion Related substances were completely separated from MCP .For MCP,the linearity of determination was over the range of 10-200 μg/ml and the recovery of the method ranged from 100.3%to 101.6%.The relative standard deviation was 0.68%(n=9).The method is accurate, reliable, repeatable, and could be readily utilized as a quality control method for MSP nasal spray .
ABSTRACT
Objective To establish a method for determination of the content and related substances in caffeine chewable tablets. Methods Agilent TC - C18 column(250 mm×4.6 mm;5μm)was used. The mobile phase was methanol- sodium dihydrogen phosphate buffer solution(10mmol/L,adjusted to pH 3.0 with phosphoric acid )(75:25,V/V),with a flow rate 1.0 ml/min,and the detection wavelength was 273 nm. The column temperature was 30℃ and the injection volume was 20 μl. Results The calibration curves showed good linearity(r=1,n=7)within ranges of 1-400 μg/ml. The average recovery of the method was about 100.04%(RSD=0.12%,n=9),and the stability of working solutions was acceptable in 24 h (RSD=1.07%,n=8). Conclusion The results indicated that the developed method could be readily utilized as a method for the quality control,including contents determination, intermediate products and stability study.