Design of a Reciprocal Injection Device for Stability Studies of Parenteral Biological Drug Products.

Formulation screening, essential for assessing the impact of physical, chemical, and mechanical stresses on protein stability, plays a critical role in biologics drug product development. This research introduces a Reciprocal Injection Device (RID) designed to accelerate formulation screening by probing protein stability under intensified stress conditions within prefilled syringes. This versatile device is designed to accommodate a broad spectrum of injection parameters and diverse syringe dimensions. A commercial drug product was employed as a model monoclonal antibody formulation. Our findings effectively highlight the efficacy of the RID in assessing concentration-dependent protein stability. This device exhibits significant potential to amplify the influences of interfacial interactions, such as those with buffer salts, excipients, air, metals, and silicone oils, commonly found in combination drug products, and to evaluate the protein stability under varied stresses.

Is roller milling - the low energy wet bead media milling - a reproducible and robust milling method for formulation investigation of aqueous suspensions?

Long-acting injectables have shown to offer a prolonged release of a drug compound up to several months, providing the opportunity to increase patient compliance for treatment of long-term and chronic conditions. Different formulation technologies have already been utilized for long-acting injectables, and especially aqueous suspensions with crystalline drug particles in the sub-micron range have sparked an interest for future development of long-acting injectables. Wet bead milling is a common top-down process used to prepare nano- and microsuspensions of crystalline drug particles with the addition of surfactants in the dispersion medium, which are working as stabilizers to prevent agglomeration or crystal growth that ultimately may influence the physical stability of nano- and microsuspensions. To examine the reproducibility of the suspensions manufactured and the behavior of their physical stability, i.e., changes in particle sizes over time, low-energy roller mill was utilized for the manufacturing of nano- and microsuspensions in the present study. Investigated formulation parameters was stabilizer type and concentration and milling parameters varied in bead size and duration of milling. The obtained results demonstrated that the physical stability of suspensions containing the two model compounds, cinnarizine and indomethacin, was highly affected by the constitution of surfactant and processing. Various size classes were obtained and accompanied by high variations between the individual samples that indicated uneven and unpredictable milling by the low-energy roller mill, limiting the possibility to prepare reproducible and physical stable suspensions. Short-term stability studies revealed clear tendencies towards reversed Ostwald ripening of suspensions stabilized with poloxamer 188 that contained cinnarizine as the drug compound, and to a smaller extent suspensions containing indomethacin. Furthermore, X-ray Powder Diffraction confirmed no alteration of the drug compounds crystal structure after roller milling for multiple days.

Wet bead milling by dual centrifugation - An approach to obtain reproducible and differentiable suspensions.

Aqueous nano- and microsuspensions containing poorly water-soluble, crystalline drug particles have in the recent years sparked an interest for the preparation of long-acting injectables (LAIs), which increase patient compliance for patients treated for long-term or chronic conditions. Nano- and microsuspensions are often prepared by top-down methods, such as wet bead milling, with the addition of stabilizers in the dispersion media, such as surfactants, which influence the particle sizes and physical stability of the suspension. To improve the efficacy of formulation screening for nano- and microsuspensions, dual centrifugation was utilized in this study whereby 40 samples could be manufactured simultaneously to support the formulation definition. Hence, the type and concentration of stabilizer as well as bead size and milling speed was investigated throughout the presented study, but also the ability of the method to produce consistent data was investigated. The obtained results demonstrated that the particle profile obtained after milling was very consistent from run to run and so was the observed stability data, i.e., running n = 1 experiment per combination could clearly be justified as a predictable approach for the formulation screening. The data also showed that the stabilizer, as well as its concentration highly influenced the physical stability of suspensions containing both the two investigated model compounds, i.e., both cinnarizine and indomethacin, where the biggest increase in particle sizes was observed within the first week. For short-term studies, polysorbate 20 was found to be a suitable stabilizer for suspensions of cinnarizine, whereas sodium dodecyl sulphate was more suitable for indomethacin suspensions immediately after the milling even with 1% (w/v) stabilizer solution, but not sufficient for short-term stability due to an insufficient stabilizer concentration. Smaller particles sizes could be achieved by milling the suspensions with the smallest bead sizes and at the highest speed of 1500 rpm without disrupting the crystal structure of the active pharmaceutical ingredient (API), which was confirmed by X-ray Powder Diffraction.

Study on formulation screening of chloral hydrate oral solution / 药学学报

Chloral hydrate is a commonly used central sedative drug before pediatric clinical examination, but its clinical safety and medication adherence are needed to focus on normally because of its poor stability and palatability. Under the premise of investigating the stability of different formulations, their palatability were also screened by using both human sensory and electronic tongue evaluation techniques. Human sensory evaluation has been conducted with the informed consent of all participants in accordance with the ethical requirements of the Good Clinical Practice for Drug Trials. The results showed that the addition of sorbitol and sucralose could effectively ensure the stability of the oral solution. Sorbitol is the main taste-masking component, and the ratio of 40% sorbitol and 0.5% sucralose can effectively mask the bitterness, astringency and spicy taste of 10% chloral hydrate oral solution. The results detected by human sensory and electronic tongue have good correlation and complementarity, and the combination of these two methods is more conducive to getting objective and reasonable conclusions.

Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery.

While all the siRNA drugs on the market target the liver, the lungs offer a variety of currently undruggable targets which could potentially be treated with RNA therapeutics. Hence, local, pulmonary delivery of RNA nanoparticles could finally enable delivery beyond the liver. The administration of RNA drugs via dry powder inhalers offers many advantages related to physical, chemical and microbial stability of RNA and nanosuspensions. The present study was therefore designed to test the feasibility of engineering spray dried lipid nanoparticle (LNP) powders. Spray drying was performed using 5% lactose solution (m/V), and the targets were set to obtain nanoparticle sizes after redispersion of spray-dried powders around 150 nm, a residual moisture level below 5%, and RNA loss below 15% at maintained RNA bioactivity. The LNPs consisted of an ionizable cationic lipid which is a sulfur-containing analog of DLin-MC3-DMA, a helper lipid, cholesterol, and PEG-DMG encapsulating siRNA. Prior to the spray drying, the latter process was simulated with a novel dual emission fluorescence spectroscopy method to preselect the highest possible drying temperature and excipient solution maintaining LNP integrity and stability. Through characterization of physicochemical and aerodynamic properties of the spray dried powders, administration criteria for delivery to the lower respiratory tract were fulfilled. Spray dried LNPs penetrated the lung mucus layer and maintained bioactivity for >90% protein downregulation with a confirmed safety profile in a lung adenocarcinoma cell line. Additionally, the spray dried LNPs successfully achieved up to 50% gene silencing of the house keeping gene GAPDH in ex vivo human precision-cut lung slices at without increasing cytokine levels. This study verifies the successful spray drying procedure of LNP-siRNA systems maintaining their integrity and mediating strong gene silencing efficiency on mRNA and protein levels both in vitro and ex vivo. The successful spray drying procedure of LNP-siRNA formulations in 5% lactose solution creates a novel siRNA-based therapy option to target respiratory diseases such as lung cancer, asthma, COPD, cystic fibrosis and viral infections.

Stability screening of pharmaceutical cocrystals.

An efficient protocol for assessing both the chemical and physical stability of cocrystalline forms of active pharmaceutical ingredients (APIs) is proposed. In this protocol, the cocrystalline material is used to prepare two standard formulations, mimicking wet granulations, to make low-dose tablets. After designed stress testing at a range of temperatures and RH conditions, degradant formation is modeled from the data using ASAPprime® to determine if the tablets have a minimum of a one-year shelf-life (25 °C/60% RH open). When the cocrystals provide a kinetic solubility enhancement over the un-complexed API, a physical assessment of the cocrystal stability is carried out using the same tablets at selected stress conditions. For this assessment, kinetic solubility (where the amount of buffer used to dissolve the tablet is adjusted to completely dissolve the cocrystalline form but leave most of the un-complexed form out of solution) changes are used to indicate whether there is a significant risk for physical instability on long-term storage. This process was exemplified using model cocrystals of APIs.

Influence of process and formulation parameters on the preparation of solid lipid nanoparticles by dual centrifugation.

A promising strategy to formulate poorly water-soluble active pharmaceutical ingredients (APIs) is the application of these substances in solid lipid nanoparticles. These drug carrier systems are commonly prepared by high-pressure homogenization above the melting temperature of the utilized lipid. While being very useful for large-scale production this method is quite resource-consuming and does not allow simultaneous processing of multiple samples, e.g. for screening purposes. For this reason, an alternative manufacturing process, dual centrifugation, is introduced to prepare solid lipid nanoparticles. The ingredients of the dispersions were directly weighed into 2 mL vessels at room temperature without the need to prepare a pre-mix emulsion. Due to an additional rotation of the samples in the heated centrifuge as well as the addition of grinding media an intensive stressing of the samples was achieved. The emulsification process was finished within 10 min with sample temperatures of up to 90 °C being obtained. Dependent on the process set-up like grinding media size, filling ratio or process temperature and the composition of the lipid formulation, the achieved particles sizes were below 200 nm and had a narrow, monomodal size distribution.

Application Progress of Texture Analyzer in Pharmaceutical Preparation Research / 中国实验方剂学杂志

Texture analyzer is a multifunctional physical property analyzer. Through a variety of test modes such as compression， puncture， shearing and stretching， hardness， adhesion， elasticity， cohesiveness and other physical property parameters are characterized. The results are objective， sensitive， and accurate， which can provide theoretical basis and reference for interpretation of basic theoretical， optimization of prescription technology and quality control research of pharmaceutical preparations. Firstly， the principles， test modes， measurement indexes and measurement data analysis methods of texture analyzer were summarized in this paper. Secondly， the application progress of texture analyzer in solid preparations， semi-solid preparations， liquid preparations， traditional Chinese medicine decoction pieces and their intermediates was described in detail， and compared with the commonly used measurement methods of physical property indicators. Finally， the application prospects of texture analyzer and its research contents to be improved were reviewed， so as to facilitate the use of texture analyzer by pharmaceutical researchers to promote the development of related fields of pharmaceutics， and to provide new ideas and methods for the research and development of pharmaceutical preparations.

Formulation Optimization of Compound Renshen Jianti Formulation and Study on Its Anti-fatigue Activity and Acute Toxicity / 中国药房

OBJECTIVE：To optimi ze the ratio of four comp onents of Compound renshen jianti formulation （Panax ginseng ， Dioscorea oppositifolia ，Lycium barbarum fruit，Alpinia oxyphylla ），and to investigate its anti-fatigue activity and acute toxicity. METHODS：The water extract of Compound renshen jianti formulation was prepared by water extraction ，concentration and decompression drying. By single factor tests ，using weight-bearing swimming time as index ，the effects of four factors were investigated，such as the amount of P. ginseng ，D. oppositifolia ，L. barbarum fruit，A. oxyphylla . On the basis of single factor tests，using comprehensive score of weight-bearing swimming time ，serum urea nitrogen content ，liver glycogen content and AUC of blood lactate after exercise as index ，the formulation was optimized by Box-Behnken response surface method. The mice was divided into blank control group （water），positive control group （Renshen hongjingtian capsules ，0.135 g/kg）and compound low-dose，medium-dose and high-dose groups [the optimal ratio of Compound renshen jianti formulation extract （called“optimal compound formulation ”for short ）4.08，8.16，12.24 g/kg，by crude drug] ，intragastric administration of drug or distilled water 20 mL/kg，once a day ，for consecutive 30 d. The weight-bearing swimming time ，the contents of serum urea nitrogen ，liver glycogen and blood lactate AUC after exercise were used to optimize its anti-fatigue activity of optimal compound formulation. The comprehensive score was calculated based on the measured data of mice in the compound formulation middle-dose group ， and the difference between it and the theoretical prediction value was compared. The mice were given optimal compound formulation intragastrically （total dose 16.00 g/kg， by extract）. The general state ， body mass change ， toxic characteristics and death of mice were observed and recorded for 14 days. Median lethal dose （LD50）and maximum tolerated dose （MTD）were measured. RESULTS ：The optimal formulation ratio of Compound renshen jianti formulation included that P. ginseng 1.5 g，D. oppositifolia 10 g，L. barbarum fruit 10 g，A. oxyphylla 3 g. Results of anti-fatigue activity validation test showed that the optimal compound formulation could significantly prolonged weight-bearing swimming time ，reduced serum content of urea nitrogen ，blood lactate content and its AUC （except for low-dose group ），while significantly increased the content of liver glycogen （P＜0.05 or P＜0.01）. Average comprehensive score of medium-dose group was 96.95，which was only 0.06％ different from the theoretical prediction value of 97.01. The results of acute toxicity test showed that there was no death in mice. The oral MTD of the optimal compound formulation was more than 15 g/kg，which was non-toxic. CONCLUSIONS ：The optimal Compound renshen jianti formulation has effective anti-fatigue activity of mice ，and has no significant toxic effect.

Redesigning food protein formulations with empirical phase diagrams: A case study on glycerol-poor and glycerol-free formulations.

Redesigning existing food protein formulations is necessary in situations where food authorities propose dose adjustments or removal of currently employed additives. Redesigning formulations involves evaluating substitute additives to obtain similar long-term physical stability as the original formulation. Such formulation screening experiments benefit from comprehensive data visualization, understanding the effects of substitute additives on long-term physical stability, and identification of short-term optimization targets. This work employs empirical phase diagrams to reach these benefits by combining multidimensional long-term protein physical stability data with short-term empirical protein properties. A case study was performed where multidimensional protein phase diagrams (1152 formulations) allowed for identification of stabilizing effects as a result of pH, methionine, sugars, salt, and minimized glycerol content. Corresponding empirical protein property diagrams (144 formulations) resulted in the identification of normalized surface tension as a short-term empirical protein property to reach long-term physical stability presumably similar to the original product, namely via preferential hydration. Additionally, changes in pH and salt were identified as environmental optimization targets to reach stability via repulsive electrostatic forces. This case study shows the applicability of the empirical phase diagram method to rationally perform formulation redesign screenings, while simultaneously expanding knowledge on protein long-term physical stability.

A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate.

The stability of live-attenuated viruses is very challenging due to thermal sensitivity; therefore, solid form is usually required (often freeze-dried products). Micropellet technology is a lyophilization technology that has the potential to provide greater flexibility in the presentation of a given vaccine particularly in multi-dose format or in combination of different vaccines. As a novel vaccine alternative process, this spray freeze-dried (SFD) micropellet technology was evaluated using as a model a yellow fever virus produced in Vero cells (vYF). Screening of excipients was performed in order to optimize physico-chemical properties of the micropellets. Sugar/polymer-based formulations induced high glass transition temperature (Tg), adequate breaking force and attrition resistance of the SFD micropellets. These mechanical parameters and their stability are of considerable importance for the storage, the transport but also the filling process of the SFD micropellets. By adding excipients required to best preserve virus infectivity, an optimal sugar/polymer-based formulation was selected to build micropellets containing vYF. Monodisperse and dried micropellets with a diameter of about 530 µm were obtained, exhibiting similar potency to conventional freeze-dried product in terms of vYF infectious titer when both solid forms were kept under refrigerated conditions (2-8 °C). Comparable kinetics of degradation were observed for vYF formulated in micropellets or as conventional freeze-dried product during an accelerated stability study using incubations at 25 °C and 37 °C over several weeks. The results from this investigation demonstrate the ability to formulate live-attenuated viruses in micropellets. Pharmaceutical applications of this novel vaccine solid form are discussed.

Rats and rabbits as pharmacokinetic screening tools for long acting intramuscular depots: case study with paliperidone palmitate suspension.

Development of prodrug of 9-hydroxyrisperidone (paliperidone) long-acting intramuscular injection has enabled delivery over four-week time period with improved compliance. The key aim of this work was to establish a reliable preclinical model which may potentially serve as a screening tool for judging the pharmacokinetics of paliperidone formulation(s) prior to human clinical work. Sparse sampling composite study was used in rats, (Wistar/Sprague-Dawley (SD; n = 10)) and a serial blood sampling study design was used in rabbits (n = 4). Animals received intramuscular injection of paliperidone palmitate in the thigh muscle at dose of 16 (rats) and 4.5 mg/kg (rabbits). Samples were drawn in rats (retro-orbital sinus) and rabbits (central ear artery) and were analysed for paliperidone using liquid chromatography-mass spectrometry/ mass spectrometry (LC-MS/MS) assay. The plasma data was subjected to pharmacokinetic analysis. Following intramuscular injection of depot formulation in Wistar/SD rats and rabbits, absorption of paliperidone was slow and gradual with median value of time to reach maximum concentration (Tmax) occurring on day 7. The exposures (i.e. area under the curve (AUC; 0-28) days) were 18,597, 21,865 and 18,120 ng.h/mL, in Wistar, SD and rabbits, respectively. The clearance was slow and supported long half-life (8-10 days). Either one of the two models can serve as a research tool for establishing pharmacokinetics of paliperidone formulation(s).

Food for thought: formulating away the food effect - a PEARRL review.

OBJECTIVES: Co-ingestion of oral dosage forms with meals can cause substantial changes in bioavailability relative to the fasted state. Food-mediated effects on bioavailability can have significant consequences in drug development, regulatory and clinical settings. To date, the primary focus of research has focused on the ability to mechanistically understand the causes and predict the occurrence of these effects. KEY FINDINGS: The current review describes the mechanisms underpinning the occurrence of food effects, sheds new insights on the relative frequency for newly licensed medicines and describes the various methods by which they can be overcome. Analysis of oral medicines licensed by either the EMA or FDA since 2010 revealed that over 40% display significant food effects. Due to altered bioavailability, these medicines are often required to be dosed, rather restrictively, in either the fed or the fasted state, which can hinder clinical usefulness. SUMMARY: There are clinical and commercial advantages to predicting the presence of food effects early in the drug development process, in order to mitigate this risk of variable food effect bioavailability. Formulation approaches aimed at reducing variable food-dependent bioavailability, through the use of bio-enabling formulations, are an essential tool in addressing this challenge and the latest state of the art in this field are summarised here.

Formulation Screening and Freeze-Drying Process Optimization of Ginkgolide B Lyophilized Powder for Injection.

The purpose of this study was to prepare ginkgolide B (GB) lyophilized powder for injection with excellent appearance and stable quality through a formulation screening and by optimizing the freeze-drying process. Cremophor EL as a solubilizer, PEG 400 as a latent solvent, and mannitol as an excipient were mixed to increase the solubility of GB in water to more than 18 times (about from 2.5 × 10-4 mol/L (0.106 mg/mL) to 1.914 mg/mL). Formulation screening was conducted by orthogonal design where the content of GB in the solution before lyophilization (using external standard method of HPLC) and reconstitution time after lyophilization were the two evaluation indexes. The optimized formulations were GB in an amount of 2 mg/mL, Cremophor EL in an amount of 16% (v/v), PEG 400 in an amount of 9% (v/v), mannitol in an amount of 8% (w/v), and the solution pH of 6.5. Through four single-factor experiments (GB adding order, preparation temperature of GB solution, adding amount, and adsorption time of activated carbon), the preparation process of GB solution was confirmed. The glass transition temperature of maximally GB freeze-concentrated solution was - 17.6°C through the electric resistance method. GB lyophilized powder began to collapse at - 14.0°C, and the fully collapsed temperature was - 13.0°C, which were determined by freeze-drying microscope. When the collapse temperature was determined, the primary drying temperature was obtained. Thereby, the freeze-drying curve of GB lyophilized powder was initially identified. The freeze-drying process was optimized by orthogonal design, the qualified product appearance and residual moisture content were the two evaluation indexes. The optimized process parameters and process were (1) shelf temperature, decreased from room temperature to - 45.0°C, at 0.5°C/min in 2 h; (2) shelf temperature increased from - 45.0 to - 25.0°C, at 0.1°C/min, maintained for 3 h, and the chamber pressure was held at 10 Pa; (3) shelf temperature was increased from - 25.0 to - 15.0°C at 0.1 °C/min, maintained for 4 h, and the chamber pressure was held at 10 Pa; and (4) shelf temperature was increased from - 15.0 to 20.0°C at 1.0 °C/min, maintained for 4 h, and the chamber pressure was raised up to 80 Pa. In these lyophilization process conditions, the products complied with relevant provisions of the lyophilized powders for injection. Meanwhile, the reproducibility was satisfactory. Post-freezing annealing had no significantly beneficial effects on shortening the freeze-drying cycle and improving the quality of GB lyophilized powder.

Current developments and applications of microfluidic technology toward clinical translation of nanomedicines.

Nanoparticulate drug delivery systems hold great potential for the therapy of many diseases, especially cancer. However, the translation of nanoparticulate drug delivery systems from academic research to industrial and clinical practice has been slow. This slow translation can be ascribed to the high batch-to-batch variations and insufficient production rate of the conventional preparation methods, and the lack of technologies for rapid screening of nanoparticulate drug delivery systems with high correlation to the in vivo tests. These issues can be addressed by the microfluidic technologies. For example, microfluidics can not only produce nanoparticles in a well-controlled, reproducible, and high-throughput manner, but also create 3D environments with continuous flow to mimic the physiological and/or pathological processes. This review provides an overview of the microfluidic devices developed to prepare nanoparticulate drug delivery systems, including drug nanosuspensions, polymer nanoparticles, polyplexes, structured nanoparticles and theranostic nanoparticles. We also highlight the recent advances of microfluidic systems in fabricating the increasingly realistic models of the in vivo milieu for rapid screening of nanoparticles. Overall, the microfluidic technologies offer a promise approach to accelerate the clinical translation of nanoparticulate drug delivery systems.

High-Throughput Screening and Analysis of Charge Variants of Monoclonal Antibodies in Multiple Formulations.

Among different biopharmaceutical products, monoclonal antibodies (mAbs) show a high level of complexity, including heterogeneity due to differences in size, hydrophobicity, charge, and so forth. Such heterogeneity can be related to both cell-based production and any of the stages of purification, storage, and delivery that the mAb is subjected to. Choosing the right formulation composition providing both physical and chemical stabilities can be a very challenging process, especially when done in the limited time frame required for a typical drug development cycle. Charge variants, a common type of heterogeneity for mAbs, are easy to detect by ion exchange, specifically cation exchange chromatography (CEX). We have developed and implemented a high-throughput CEX-based approach for the rapid screening and analysis of charge modifications in multiple formulation conditions. In this work, 96 different formulations of antistreptavidin IgG1 and IgG2 molecules were automatically prepared and analyzed after incubation at high temperature. Design of experiment and statistical analysis tools have been utilized to determine the major formulation factors responsible for chemical stability of antibodies. Regression models were constructed to find the optimal formulation conditions. The methodology can be applied to different stages of preformulation and formulation development of mAbs.

Screening Vaccine Formulations in Fresh Human Whole Blood.

Monitoring the immunological functionality of vaccine formulations is critical for vaccine development. While the traditional approach using established animal models has been relatively effective, the use of animals is costly and cumbersome, and animal models are not always reflective of a human response. The development of a human-based approach would be a major step forward in understanding how vaccine formulations might behave in humans. Here, we describe a platform methodology using fresh human whole blood (hWB) to monitor adjuvant-modulated, antigen-specific responses to vaccine formulations, which is amenable to analysis by standard immunoassays as well as a variety of other analytical techniques.

Study on Formulation of Xiqingguo Buccal Tablet / 中国药房

OBJECTIVE:To study the formulation of Xiqingguo buccal tablet,optimize the proportion and quantity of main materials. METHODS:Using appearance,hardness,dissolution and taste as investigation indexes,orthogonal design was adopted to optimize the proportion and quantity of main thinner(lactose,mannitol),wetting agent(ethanol),lubricant(magnesium stea-rate),flavoring agent(aspartame),and critical relative humidity was detected. RESULTS:By wet granulation,the optimal formu-lation were as follows as the ratio of lactose and mannitol was 1:3,ethanol volume fraction was 60%,the dosage of menthol, magnesium stearate,aspartame and orange essence was 0.4%,0.9%,2.0%,0.4%;it was proven that the total score of 3 batches of samples were 2.67,2.67,2.70 (RSD=0.65%,n=3),respectively. The critical relative humidity of granule was 60%. CON-CLUSIONS:The Xiqingguo buccal tablet prepared by optimal prescription meets the requirements.

Formulation Optimization of Budesonide Sustained-release Tablet by Central Composite Design-response Surface Method / 中国药房

OBJECTIVE:To optimize the formulation of Budesonide sustained-release tablet. METHODS:Using the cumula-tive releases in 2,4,8 h as investigation indexes,central composite design-response surface method was used to optimize the amount of hydroxypropylcellulose L(HPC-L),amount of soybean phosphatides,and filler(fixed total 200 mg)lactose- micro-crystalline cellulose mass ratio in the formulation of Budesonide sustained-release tablet,and the verification test was conducted. The release behaviors of prepared sustained-release tablet and original preparation in pH 7.2,7.0,6.8 phosphate buffer were com-pared. RESULTS:The optimal formulation was as follow as budesonide of 9 mg,HPC-L of 46.49 mg,soybean phosphatides of 9.23 mg,filler lactose-microcrystalline cellulose mass ratio of 1:2.9;the cumulative releases in 2,4,8 h were 21.9%,50.1%, 99.5%,the relative errors with predicted values (22.0%,50.0%,98.5%) were 0.45%,0.20%,1.02%(n=3),respectively. Compared with cumulative release of original preparation,the f2 was higher than 50. CONCLUSIONS:Budesonide sustained-re-lease tablet is successfully prepared,which shows similar release behavior to original preparations.

Optimization of moxifloxacin hydrochloride tablets by formulationscreening and preparation process / 国际药学研究杂志

Objective To screen prescriptions for moxifloxacin hydrochloride tablets and optimize its preparation technology. Methods Taking the angle of repose,tap density,hardness,friability,disintegration time,tablet weight difference,and dissolution rate as indexes,the amount of each component,binder solvent,amount of binder,size of the mesh for granulation and particle drying process were investigated. The optimal formulation and process were determined based on the above results. Results With water as the binder solvent,binder volume of 6 ml,screen mesh number of 26 mesh,and finally drying 1 h at 50℃,the indicators of the tablet prepared met the quality requirements of tablet in the second part of the Pharmacopoeia of People′s Republic of China the 2015 ver-sion. And the dissolution profile was in good agreement with the commercially available preparation. Conclusion The quality of moxi-floxacin hydrochloride tablets prepared by the optimal formulation and process in this study is in accordance with the standard. The pre-scription and process can be used for the preparation of generic drugs of moxifloxacin hydrochloride tablets.