Full-factor design of experiment application in the development of printing ink for binder jetting 3D printed preparation / 药学学报

The development of printing ink is a challenge for binder jetting 3D printed preparations, which directly determines the quality of the printed product. This study adopted a 23 full-factor Design of Experiment (DoE) with three central points to optimize the printing ink composition of levetiracetam 3D printed dispersible tablet based on the concept of Quality by Design. Firstly, using polyvinyl pyrrolidone K30, glycerin and polysorbate 20 as independent variables based on 40% (v/v) isopropanol aqueous solution, and weight variation, hardness, friability and dispersion uniformity of the printed tablets were used as dependent variables. Then obtained the design space of the printing ink prescription by DoE model analysis, and the response optimizer was used to obtain the optimal printing ink prescription: isopropanol aqueous solution containing 0.1% (w/w) polyvinyl pyrrolidone K30 and 4.0% (w/w) glycerin. The jetting mechanism and wettability of the printing ink were analyzed, and different strengths of personalized 3D printed tablets were prepared and characterized, which verified the rationality of the printing ink formulation. This study provided a reference for the development of printing ink for binder jetting 3D printed preparations.

Effect of needling technique on diabetic gastroparesis and transmembrane protein 16A / 中国针灸

OBJECTIVE@#To observe the therapeutic effect of needling technique (acupuncture for regulating spleen and stomach) on diabetic gastroparesis (DGP), and to explore its possible mechanism.@*METHODS@#A total of 128 patients with DGP were randomized into an observation group (64 cases, 4 cases dropped off) and a control group (64 cases, 4 cases dropped off). On the basis of intervention on controlling blood glucose by western medication, needling technique was adopted at Zhongwan (CV 12), Zusanli (ST 36), Yinlingquan (SP 9), Xuehai (SP 10), Sanyinjiao (SP 6), Diji (SP 8), etc. in the observation group, once a day. Mosapride citrate dispersible tablet 5 mg was given orally 3 times a day in the control group. The treatment was given 6 times a week in the both groups, and totally 4-week treatment was required. Before and after treatment, the DGP symptom score, serum content of transmembrane protein 16A (ANO1) were observed, and the clinical therapeutic effect and the safety were evaluated in the both groups.@*RESULTS@#After treatment, the each subitem score (belching, abdominal distension, inappetence, nausea and vomiting, epigastric pain, abnormal defecation) and the total score of DGP symptom were decreased in both groups (<0.05), the subitem scores of belching, abdominal distension, inappetence, nausea and vomiting and the total score in the observation group were lower than those in the control group (<0.05). After treatment, the serum contents of transmembrane protein 16A were reduced in both groups (<0.05), and that in the observation group was lower than the control group (<0.05). The total effective rate was 86.7% (52/60) in the observation group, which was superior to 70.0% (42/60) in the control group (<0.05). Subcutaneous hematoma occurred in 5 cases in the observation group, which was improved after cold compress without other particular intervention.@*CONCLUSION@#The therapeutic effect of needling technique on improving symptoms in patients with diabetic gastroparesis is superior to mosapride citrate dispersible tablet, its mechanism may be related to alleviating the damage of interstitial cells of Cajal (ICC).

Study on puerarin dispersible tablet based on solubilization effect of glycyrrhizic acid / 中国中药杂志

Based on the fact that glycyrrhizic acid can form micelles in aqueous solution and play a role in solubilization, the optimal compatibility ratio between puerarin and glycyrrhizic acid was screened to prepare puerarin-glycyrrhizic acid dispersible tablets and investigate the dissolution of puerarin. The particle size, Zate potential and puerarin dissolution were compared among the micellar solutions with mass ratio of 7∶1, 6∶1, 5∶1, 4∶1, 3∶1 and 2∶1(puerarin to glycyrrhizic acid), and it was found that when the mass ratio of puerarin and glycyrrhizic acid was 5∶1, the micelle showed smallest particle size, uniform distribution, and largest puerarin dissolution, so mass ratio of 5∶1 was determined as the optimal condition. The formulation of puerarin-glycyrrhizic acid dispersible tablets was optimized by single factor and orthogonal test: puerarin 100.0 mg, glycyrrhizin 20.0 mg, polyvinylpolypyrrolidone 24.0 mg as disintegrating agent, microcrystalline cellulose 135.0 mg as stuffing bulking agent, hydroxypropyl methyl cellulose 18.0 mg as adhesive agent, magnesium stearate 2.7 mg as lubricant, and tablet weight of 300.0 mg. High-performance liquid chromatography(HPLC) method was used to determine the content of puerarin in dispersible tablets. Puerarin showed a good linear relationship(r=0.999 8) in the range of 15.5-248 g·L~(-1), with high precision(RSD<2.0%) and good repeatability(RSD<2.0%), and the recovery rate was 101.1%, RSD 0.89%. There was no significant difference in the quantity of puerarin in different batches of puerarin-glycyrrhizic acid dispersible tablets. When the artificial gastric juice was used as the dissolution medium, the dissolution of puerarin in puerarin-glycyrrhizic acid dispersible tablets could reach over 85% within 15 min. When phosphate buffer(pH 6.8) was used as the dissolution medium, the dissolution of puerarin in the puerarin-glycyrrhizic acid dispersible tablets had a faster dissolution rate in vitro, 99.8% in 30 min. Therefore, puerarin-glycyrrhizic acid dispersible tablets could improve the dissolution of puerarin in vitro due to the solubilization effect of glycyrrhizic acid.

Pharmacokinetics study of mycophenolic acid in early renal transplant patients / 中国药学杂志

OBJECTIVE: To investigate the pharmacokinetic characteristics of enteric-coated sodium mycophenolate(EC-MPS) or mycophenolate mofetil (MMF) dispersible tablets after multiple oral doses in early renal transplant patients, providing references for the rational use of the study drugs in clinical practice. METHODS: Thirty-eight first-time renal transplant patients were selected and randomly divided into EC-MPS group (n=18) or MMF dispersible tablets group (n=19). The patients received EC-MPS (540 mg, q12h) or MMF dispersible tablets (750 mg, q12h), combined with tacrolimus and methylprednisolone to prevent acute rejection, respectively. Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after oral administration on the postoperative day 5. Enzyme multiplied immunoassay technique (EMIT) was employed to determine the plasma concentration of MPA. The main pharmacokinetic parameters of the two durgs were assessed. RESULTS: Pharmacokinetic parameters on the postoperative day 5 of EC-MPS and MMF dispersible tablet were as follows: AUC0-12 h were(43.62±16.20) and(42.02±14.40)mg•h•L-1(P>0.05);ρmax were (17.85±11.32) and (13.96±5.11) mg•L-1(P>0.05);tmax were (2.72±1.74) and(1.32±0.42)h(P0.05); ρ12were(1.84±2.09) and (1.81±1.76) mg•L-1(P>0.05); CL were (14.12±5.30) and (19.66±5.99) L•h-1(P<0.05). Most of the patients revealed a second small peak in the 4-12 h after taking MPA in the two study groups. CONCLUSION: There are large individual differences of pharmacokinetic between EC-MPS and MMF dispersible tablets in early renal transplant patients. It is necessary to carry out therapeutic drug monitoring of MPA to guide the adjustment of drug dosage.

Pharmacokinetics Study of Mycophenolate Mofetil Dispersible Tablets in Early Renal Transplant Patients / 中国药学杂志

OBJECTIVE: To develop an UPLC method for the determination of mycophenolic acid(MPA) for studying the pharmacokinetics of mycophenolate mofetil(MMF) dispersible tablets after multiple oral doses in early kidney transplant recipients for the rational use in the clinical practice. METHODS: A total of 15 Chinese postoperative renal transplant recipients were given a multiple-dose of MMF (750 mg, q12 h) for 6 d. Their blood specimens (2 mL) were collected at 0 and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after drug oral administration on day 7. The concentrations of MPA in plasma were determined using UPLC-UV. The main pharmacokinetic parameters were assessed. RESULTS: Determination of MPA had good linearity in the concentration range of 0.1-40 μg·mL-1, lower limit of quantization was 0.10 μg·mL-1.The main pharmacokinetic parameters on day 7 of MMF dispersible tablets were as follows: AUC0-12 h was (24.63±9.51) μg·h·mL-1, ρmax was (6.51±3.27) μg·mL-1, tmax was (1.83±1.30) h, ρ0 was (1.26±0.99) μg·mL-1, CL was (34.66±12.45) L·h-1. Most of the patients revealed a second small peak in the 4-12 h. CONCLUSION: This established method is simple, rapid and suitable for determination of MPA in human plasma.Interindividual variability in AUC0-12 h, ρmax and ρ0 values was considerable in the early renal transplant patients. The MPA exposures under the fixed dose of MMF are low. It is necessary to monitor the MPA-AUC0-12 h to guide the adjustment of drug dosage.

Determination of Related Substances in Lovastatin Tablet by HPLC / 中国药房

OBJECTIVE:To establish a method for the determination of related substances in Lovastatin tablet. METHODS:HPLC was performed on the column of Waters XTerra? MS C18 with mobile phase A of 0.01%Phosphoric acid solution and B of acetonitrile(gradient elution)at a flow rate 1.0 ml/min,column temperature was 40 ℃,the detection wavelength was 238 nm,and the injection volume was 10 μl. RESULTS:The impurity components were well separated in principal components;the linear range of lovastatin was 17.5-700 μg/ml(r=0.9999);RSDs of precision,stability and reproducibility tests were lower than 1%;recov-ery was 99.30%-100.67%(RSD=0.4%,n=9). CONCLUSIONS:The method is reproducible with good durability and high preci-sion,and can be used for the quality control of Lovastatin tablet.

Formulation and evaluation of taste mask pellets of granisetron hydrochloride as oro dispersible tablet

Orally disintegrating systems have carved a niche amongst the oral drug delivery systems due to the highest compliance of the patients, especially the geriatrics and pediatrics. In addition, patients suffering from dysphagia, motion sickness, repeated emesis and mental disorders prefer these medications because they cannot swallow large quantity of water. Further, drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated in these dosage forms. However, the requirements of formulating these dosage forms with mechanical strength sufficient to withstand the rigors of handling and capable of disintegrating within a few seconds on contact with saliva are inextricable. The purpose of this research was to mask the bitter taste of granisetron hydrochloride. To mask the taste Kollicoat(r) Smartseal 30D was used as coating polymer for pellet coating. The coated pellets of the drug was directly compressed with different superdisintegrant as AC-Di-Sol, Explotab and Kollidon CL in different concentration 5.0-7.5% w/w into an ODT. The prepared tablets were evaluated for hardness, friability, weight variation, wetting time, wet absorption ratio, in-vitro disintegration time and in vitro dissolution studies. Tablets exhibited quick disintegration characteristics with Kollidon CL in concentration 7.5% w/w i.e., within 20 seconds, which is characteristic of orally disintegrating dosage forms. More than 98% of drug was released from the formulations within 15 minutes. Formulations subjected to stability testing as per the ICH guidelines for 3 months, indicated stability with no change in taste, hardness, drug content, disintegration time and dissolution profiles. Thus, the results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated dosage forms in the oral cavity.

Sistemas de desintegração oral têm um nicho entre os sistemas de administração de medicamentos por via oral devido à maior aceitação dos pacientes, especialmente os de geriatria e pediatria. Além disso, pacientes que sofrem de disfagia, enjoo de movimento, emese repetida e distúrbios mentais preferem estes medicamentos porque não podem engolir grande quantidade de água. Além disso, os fármacos que exibem absorção satisfatória a partir da mucosa oral ou que se destinam a ação farmacológica imediata podem ser vantajosamente formulados nestas formas de dosagem. No entanto, a formulação destas formas farmacêuticas exige-lhes resistência mecânica suficiente para suportar os rigores do manuseio e capacidade de desintegrar dentro de alguns segundos em contato com a saliva. O objetivo desta pesquisa foi o de mascarar o gosto amargo de cloridrato de granisetrona. Para mascarar o sabor, utilizou-se Kollicoat smartseal 30D como polímero para io revestimento dos péletes. Os péletes revestidos do fármaco foram diretamente comprimidos com superdesintegrante diferente como Ac-Di-Sol, Explotab e Kollidon CL, em diferentes concentrações 5.0-7.5% m/m em comprimidos de dispersão oral (ODT). Os comprimidos preparados foram avaliados quanto à dureza, friabilidade, variação de peso, ao tempo de umedecimento, à razão de absorção de umidade, ao tempo de desintegração in vitro e em estudos de dissolução in vitro. Os comprimidos apresentaram características de desintegração rápida com Kollidon CL, em concentração de 7,5% m/m, ou seja, dentro de 20 segundos, o que é característico para formas farmacêuticas de desintegração oral. Mais do que 98% do fármaco foi liberado a partir das formulações no prazo de 15 minutos. Formulações submetidas a testes de estabilidade de acordo com as diretrizes da ICH por 3 meses indicaram estabilidade sem alteração no sabor, dureza, teor de fármaco, tempo de desintegração e perfis de dissolução. Assim, os resultados demonstraram que o mascaramento de gosto foi bem-sucedido e atingiu-se rápida desintegração das formas de dosagem na cavidade oral.

Bioequivalence of Cefdinir Dispersible Tablets in Healthy Volunteers / 中国药房

OBJECTIVE:To study the pharmacokinetics and the bioequivalence of cefdinir dispersible tablets in healthy volunteers.METHODS:Microbiological assay method was used to determine the plasma concentration at different time in 20 healthy volunteers after oral administration of single dose of 400mg of cefdinir dispersible tablets(test preparation) and cefdinir capsule(reference preparation) by cross-over way.RESUTLS:The concentration-time curves of test preparation and reference preparation of cefdinir fitted one compartment open model.The pharmacokinetic parameters of the test preparation vs.the reference preparation were as follows:tmax(3.48?0.53)h vs.(3.60?0.48)h,Cmax(2.10?0.32)mg?L-1 vs.(2.15?0.26)mg?L-1.t1/2ke(2.41?0.39)h vs.(2.33?0.41)h,AUC0～12(9.51?1.65)mg?h?L-1 vs.(10.05?1.72)mg?h?L-1,AUC0～∞(10.43?1.62)mg?h?L-1 vs.(11.01?1.81)mg?h?L-1,respectively.The relative bioavailability of cefdinir dispersible tablet as against its reference preparation was(96.03?14.89)%.CONCLUSION:The two preparations of cefdinir were proved to be bioequivalent.

Preparation and Quality Control of Erchen Dispersible Tablet / 中国药房

OBJECTIVE:To prepare erchen dispersible tablet and establish its quality control method.METHODS:cCMC-Na was used as disintegrating agent,and polyvinyl pyrrolidone as well as other adjuvants were added to prepare the tablet;The content of hesperidin was determined by HPLC,and the stability of the finished product was also evaluated.RESULTS:The sample size of hesperidin was linear in the range of1?g～80?g,the average recovery was99.98%,RSD=0.98%;The preparation showed good stability.CONCLUSION:The present formulatiom is rational,and the preparation technic is simple,the finished product meets the standards of Chinese Pharmacopenia.

Preparation and dissolution test of compound Yuxingcao dispersible tablets / 中华中医药杂志

Objective: To prepare the compound Yuxingcao dispersible tablets and investigate the dissolution of baicalin in vitro. Methods: The formulation of dispersible tablets was optimized by an orthogonal design test in terms of disinterating time.Results: The optimal disintegrants were composed of CMS-Na 5%,MCC 20%,L-HPC 10%,and disintegration time of prepared compound Yuxingcao dispersible tablets followed the quality specification of dispersible tablet in Chinese Pharmacopoeia 2005. The in vitro dissolution test indicated that more than 95% of baicalin dissolved in 3 minute from dispersible tablets. Concolusion: The formulation and preparation process of compound Yuxingcao dispersible tablets were simple and feasible.

Preparetion of Ketanning dispersible tablet / 中华中医药杂志

Objective: To optimize the formulation of Ketanning dispersible tablet.Methods: The Ketanning dispersible tablet was prepared by using wet granules.The formulation and preparation technology was optimized by using orthogonal design which took the situation of granules,appearance of taablets,the disintegrating time and the tensile strength as indices.Results: The optimized formulation contained,10%MCC,10% PVPP is inner,10% PVPP is outer,1% magnesium stearate.The tensile strength,the disintegrating time were 70N and 3min respectively.Conclusion: It is successful to prepare immediate release tablet.The optimized formulation is rational and stable,the tablet could be released quickly.

Preparation of rhubarb lactobacillin dispersible tablets / 中华中医药杂志

Objective: To obtain the optimum prescription of the rhubarb lactobacillin dispersible tablets.Methods: The kind and amount of the excipient were investigated by using the disintegrating time to establish the optimum prescription and preparation process.Results: The tablets were prepared by compressing moist granulation with the PVPP and CMS-Na as the disintegrant,MCC as diluent,sodium alginate as sweller,magnesium stearate as lubricant and 80% alcohol as adhesive agent.The preparation complied with the requirement of Pharmacopeia of the People's Republic of China(2005edition).Conclusion: This prescription of the tablet is reasonable and the preparation process is feasible.

Assessment on Bioequivalence of Tegaserod Maleate Dispersible Tablets in Human Body / 中国药房

OBJECTIVE: To study the bioequivalence of tegaserod maleate dispersible tablets in healthy volunteers.METHODS: A single oral dose of 6mg test or reference preparations of tegaserod maleate was given to 22 healthy volunteers in a randomized crossover study.The plasma concentrations of tegaserod were determined by LC/MS/MS assay.RESULTS: The main pharmacokinetic parameters of test and reference products were as follows: tmax(0.86? 0.22) and(1. 01? 0.24) h;Cmax(2.21? 0.69) and(2.05? 0.64) ng? mL1;AUC0～ 17(6.35? 2.48) and(6.47? 1.99) ng? h? mL-1,AUC0～ ∞(6.69? 2.59) and(6.70? 2.03) ng? h? mL-1,respectively.The relative bioavailability of test to reference preparation was(98.2? 22.1) %.CONCLUSION: The reference preparation and the test preparation are bioequivalent.

Preparation and Observation of Dissolution Characteristics of Ganciclovir Dispersible Tablets in Vitro / 中国药房

OBJECTIVE:To prepare ganciclovir dispersible tablet and to observe its dissolution property in vitro.METHODS:The dosage of microcrystalline cellulose and crospolyvinylpyrrolidone in the formula were optimized by orthogonal test;The content of ganciclovir was determined by UV spectrophotometry method;Dissolution rates were compared among ganciclovir dispersible tablet,Ganciclovir common tablet and Ganciclovir capsule.RESULTS:The optimized formula dosage of microcrystalline cellulose and crospolyvinylpyrrolidone were40%and10%respectively;The linear concentration range for ganciclovir was2～20?g/ml(r=0.9999,n=6);The average recovery was(100.21?0.38)%;The mean values of intraday and the inter-day precision were0.22%and0.32%respectively;The ganciclovir dispersible tablet could completely disinte-grated within30s,T 50 was(0.03?0.001)min and T d was(0.18?0.006)min,which were all lower than those of the common tablet and capsule(P

Improvement of the Formulation of Clarithromycin Dispersible Tablets / 中国药房

OBJECTIVE:To obtain an optimum formulation of clarithromycin dispersible tablets METHODS:The preparation process was set by way of screening formulation and a formula with substitution of LS-HPC for starch was adopted RESULTS:The results showed that the substitution of LS-HPC for starch was the most preferable formulation The hardness and the friability of the tablets were improved The external apperance of unfilled corner and torn edge of the unimproved tablets was resolved CONCLUSION:Modified formulation is favorable for improving the quality of the product

Study on the Preparation Technique of Tanshinone Dispersible Tablets / 中国药房

OBJECTIVE: To study the preparation technique of tanshinone dispersible tablets.METHODS: Taking the disintegration time - limit, in vitro dissolubility and suspensibility as indices, the formula of tanshinone dispersible tablets was screened by orthogonal design.RESULTS The dispersible tablets could completely disintegrate within 30 seconds and pass through 710m seive mesh, which all conformed to the requiremtes of BP(1993) .The in vitro dissolubility of this product was superior to that of ordinary tablets obviously .CONCLUSION: The preparation technique of tanshinone dispersible tablets is mature and the quality is reliable.

Preparation and in Vitro Dissolution Characteristics of Famotidine Dispersible Tablets / 中国药房

OBJECTIVE:To study the preparation of famotidine dispersible tablets and to observe the dissolution characteristics in vitro METHODS:To optimize the conditions for preparation by orthogonal design RESULTS:The tablets could completely disintegrate within 1 min;In vitro dissolution test showed T50=0 56min CONCLUSION:In comparison with commercial famotidine tablets,the dispersible tablets prepared in optimum condition were rapid in disintegration and homogenous in dispersal

Determination of Geniposide in Bazheng Dispersible Tablet by HPLC / 中药新药与临床药理

Objective To establish a method for the determination of geniposide in Bazheng Dispersible Tablet by HPI,C. Methods The HPLC was performed on a Hypersil ODS column(250 mm?4 mm,5?m).The mobile phase was acetoni- tril-water(11:89).The detection wavelength was at 238 nm and flow rate was 1.0 mL/min.Results Geniposide showed a good linearity in the range of 0.046～0.46?g,and r=0.999 9.The average recovery was 99.54%,and RSD was 1.42%。Conclusion This method is accurate and can be used for the quality control of Bazheng Dispersible Tablet.

Preparation and bioavailability of ibuprofen dispersible tablet in rabbits / 第二军医大学学报

Objective: To prepare ibuprofen dispersible tablet and compare its pharmacokinetics and bioavailability with market tablets in rabbits. Methods: According to inspection of factors and orthogonal design, optimal formulation was decided. A randomized crossover and self control design was used. Eight healthy rabbits were single oral dosed with 100 mg ibuprofen dispersible tablet or market tablet, respectively. The plasma drug concentration was determined by HPLC method. The pharmacokinetic parameters were calculated by 3P87 program and the bioequivalence was assessed by NDST5.0 program. Results: A one compartment open model was adopted and the pharmacokinetic parameters of dispersible tablet and market tablet were as follows: c max were (9.79?2.25) and (4.54?1.50) ?g/ml; t max were (0.27?0.07) and (2.03?0.53) h; t 1/2 were (6.65? 2.14) and (9.17?4.38) h; AUC 0~∞ were (94.11?28.38) and (65.20?18.38) ?g?h?ml -1 , respectively. Ralative bioavailability of the dispersible tablet was 164.11% compared to market tablet. Conclusion: Ibuprofen dispersible tablet is administrated easily and absorbed quickly, and its bioavailability is far more better than the market one. [

Determination of Gallic Acid in Gongyanping Dispersible Tablet by HPLC / 中药新药与临床药理

Objective To establish a method for the determination of gallic acid in Gongyanping Dispersible Tablet by HPLC.Method A HPLC method was performed on Hypersil ODS column(4.0?250 mm,5 ?m).The mobile phase was acetonitrile(0.2 %CH3OH)-water solution of 0.1 %triethylamine and 0.1 %phosphoric acid(1 ∶99).The detection wavelength was 220 nm and flow rate was 1.0 mL/min.Results Gallic acid showed a good linearity in the range of 0.022～0.352 ?g,r=0.999 9.The average recovery was 99.70 %,and RSD was 1.61 %.Conclusion This method is effective and can be used for the quality control of Gallic acid in Gongyanping Dispersible Tablet.