Comparative Evaluations of Aqueous Film Coated Tablet Formulations by High Humidity Aging

Compressed tablets of ticlopidine hydrochloride were coated with three aqueous film coating formulations and aged under 95% relative humidity at 23° and 37°. The in vitro dissolution of the drug from tablets coated with the formulation containing polymethacrylic acid esters before aging was slower than the tablets coated with the formulations containing hydroxypropyl methylcellulose or ethylcellulose dispersion. On aging, the in vitro drug dissolution of the coated and uncoated tablets decreased and the decrease depended on the film forming excipient in the coating formulation and the temperature of aging. The tablets coated with the formulation containing polymethacrylic acid esters dissolved very slowly after aging. Higher moisture contents of the tablets after aging under 95% relative humidity at 23° compared to 37° resulted in a consistently lower tablet crushing strength. The tablets coated with the formulation containing 10% hydroxypropy1 methylcellulose showed a smaller decrease in the tablet crushing strength on aging compared to the other two formulations.     

III. Segregation of Active Constituents from Tablet Formulations During Grinding: Effects on Coated Tablet Formulations

Abstract

Grinding or milling coated tablets in preparation for their assay can cause the physical separation of an active ingredient from the coating and other tablet components. This phenomenon has been shown to partially account for the poor reproducibility between duplicate assays, and for discrepancies among assays for the same group of tablets but which were composited by different methods.

The effect of compositing methods on the assay results is shown with commercial enteric coated aspirin tablets from various manufacturers. Samples for assay were prepared by manual grinding with a glass mortar and pestle, mechanical grinding with an electric tablet grinder, direct dissolution of the tablets in a suitable solvent, and uncoating of the tablets with an organic solvent prior to their manual grinding.

Suggestions are offered to minimize the effects of segregation of an active tablet ingredient during grinding or milling on the assay results.     

III. Segregation of Active Constituents from Tablet Formulations During Grinding: Effects on Coated Tablet Formulations

Grinding or milling coated tablets in preparation for their assay can cause the physical separation of an active ingredient from the coating and other tablet components. This phenomenon has been shown to partially account for the poor reproducibility between duplicate assays, and for discrepancies among assays for the same group of tablets but which were composited by different methods.

The effect of compositing methods on the assay results is shown with commercial enteric coated aspirin tablets from various manufacturers. Samples for assay were prepared by manual grinding with a glass mortar and pestle, mechanical grinding with an electric tablet grinder, direct dissolution of the tablets in a suitable solvent, and uncoating of the tablets with an organic solvent prior to their manual grinding.

Suggestions are offered to minimize the effects of segregation of an active tablet ingredient during grinding or milling on the assay results.     

Effect of Aqueous Film Coating Conditions on Water Removal Efficiency and Physical Properties of Coated Tablet Cores Containing Superdisintegrants

Few studies have examined the effect of aqueous film coating process conditions on the physical integrity of the final coated product. Characterization of the aqueous film coating process was previously carried out by selecting water removal efficiency as the response variable to detect and monitor moisture accumulation in the tablet bed [1]. In this study, regression techniques were utilized to obtain the relationship between some physical characteristics of aqueous film coated tablet cores that contained superdisintegrant and several process parameters such as inlet air temperature, spray rate, and pan speed. Tablet response variables measured included residual moisture content, tensile strength and percent porosity. Predicted values of these properties were plotted as a function of the inlet air temperature and the coating solution spray rate. The correlations between the coated tablet response variables and the water removal efficiency of the coating process indicated that coated tablet properties such as residual moisture content, tensile strength, and porosity were linearly correlated with the water removal efficiency of the coating process, which is indicative of the environmental coating conditions present in the coating pan.     

Effect of Aqueous Film Coating Conditions on Water Removal Efficiency and Physical Properties of Coated Tablet Cores Containing Superdisintegrants

Abstract

Few studies have examined the effect of aqueous film coating process conditions on the physical integrity of the final coated product. Characterization of the aqueous film coating process was previously carried out by selecting water removal efficiency as the response variable to detect and monitor moisture accumulation in the tablet bed [1]. In this study, regression techniques were utilized to obtain the relationship between some physical characteristics of aqueous film coated tablet cores that contained superdisintegrant and several process parameters such as inlet air temperature, spray rate, and pan speed. Tablet response variables measured included residual moisture content, tensile strength and percent porosity. Predicted values of these properties were plotted as a function of the inlet air temperature and the coating solution spray rate. The correlations between the coated tablet response variables and the water removal efficiency of the coating process indicated that coated tablet properties such as residual moisture content, tensile strength, and porosity were linearly correlated with the water removal efficiency of the coating process, which is indicative of the environmental coating conditions present in the coating pan.     

Optimization of Tablet Formulations Containing

Abstract

An optimized direct compression tablet formulation of a conventional theophylline tablet was developed using the technique of response surface methodology and successive quadratic programming (SQP). The response surfaces were obtained from fitting data generated from a secondorder uniformprecision rotatable hexagonal experimental design. The tablet formulation was optimized for mean in vitro dissolution time using disintegration time, ejection force, friability and hardness, as constraints within the experimental region by the SQP technique. The response surface model was validated by preparing and evaluating the predicted formulation. The characteristics of the tablet formulation were analyzed by principal component analysis. Sensitivity analysis for the optimal solution was performed for each constraint, while all remaining constraints were held constant. The robustness of the response surface model was evaluated by simulation for error in the compression force values.     

Optimization of Tablet Formulations Containing

An optimized direct compression tablet formulation of a conventional theophylline tablet was developed using the technique of response surface methodology and successive quadratic programming (SQP). The response surfaces were obtained from fitting data generated from a secondorder uniformprecision rotatable hexagonal experimental design. The tablet formulation was optimized for mean in vitro dissolution time using disintegration time, ejection force, friability and hardness, as constraints within the experimental region by the SQP technique. The response surface model was validated by preparing and evaluating the predicted formulation. The characteristics of the tablet formulation were analyzed by principal component analysis. Sensitivity analysis for the optimal solution was performed for each constraint, while all remaining constraints were held constant. The robustness of the response surface model was evaluated by simulation for error in the compression force values.     

Studies of Floating Dosage Forms of Furosemide: In Vitro and In Vivo Evaluations of Bilayer Tablet Formulations

For the purpose of enhancement the bioavailability of furosemide (FR), a floating dosage form with controlled release of FR was designed in this study. Because of the lower solubility of active material in the gastric medium, it was first enhanced by preparing an inclusion complex of FR with beta-cyclodextrin (β-CD) in a 1:1 proportion using the kneading method. Following the design of dosage form, bilayer floating tablets were prepared. After dissolution rate studies were performed using the continuous flow-through cell method, the formulation that provided delivery of active material near the target profile was given to six healthy male volunteer subjects, and in vivo tests were performed. It was determined by radiographs that floating tablets prepared by adding BaSO₄ stayed in the stomach for 6 hr. Further, values of the area under the plasma concentration-time curve (AUC) obtained with the floating dosage form were about 1.8 times those of the conventional FR tablet in blood analyses; maximum and minimum plasma concentrations were also found to be between the desired limits. In urine analyses, the peak diuretic effect seen in classical preparations was decreased and prolonged in floating dosage forms. Also, a considerably significant correlation was detected between in vivo results and in vitro data of the dissolution rate, and it was concluded that the modified continuous flow-through cell method is usable for in vitro dissolution rate tests of floating dosage forms.     

A Comparative Study of the use of Enset and Potato Starches in Tablet Formulations

Enset and potato starches have been compared as binding agents and disintegrants in tablets made with paracetamol and chloroquine phosphate. Tablet crushing strengths, friabilities and disintegration times have been measured. The results show that enset starch can be used both as a binding agent and disintegrant. It has a better binding ability than potato starch, giving tablets of lower porosity. However because of this, tablets containing enset starch disintegrate more slowly.     

溶胶－凝胶法制备薄膜湿敏元件的研究

用溶胶－凝胶法制备了Ｒ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系（Ｒ＝Ｌｉ，Ｎａ，Ｋ）薄膜湿敏元件，研究了它们的感湿特性，对薄膜的结构、导电机理进行了讨论．获得的湿敏元件具有响应快、滞后小和灵敏度高等优点．     

高湿度条件下HTV硅橡胶材料电晕老化特性

复合绝缘子在我国电网中已得到大规模应用,高湿度条件下运行中的绝缘子两端在强电场条件下极易发生电晕放电,使绝缘子外套硅橡胶材料劣化,严重时可导致绝缘子闪络,威胁电网的安全运行.以一种复合绝缘子外套用硅橡胶材料为试品,采用多针-板电极,在高湿度(RH>95％)环境中对其进行100 h的电晕老化试验,并采用静态接触角、 扫描...     

Comparative Study on the Bioequivalence of Two Formulations of Pioglitazone Tablet in Healthy Thai Male Volunteers

The bioequivalence study of two 30 mg pioglitazone formulations was determined in healthy Thai male volunteers after a single dose administration in a randomized cross-over study with a 1-week washout period. Due to the high variability of the rate and extent of absorption of pioglitazone, an add-on subject study was required to assess bioequivalence. Reference product (Actos®, Takeda Chemical Industries, Ltd., Osaka, Japan) and test product (Glubosil®, Silom Medical Co. Ltd., Bangkok, Thailand) were given to 35 volunteers after overnight fasting. Blood samples were collected at specified time intervals. Plasma was analyzed for pioglitazone concentration using a validated HPLC method. Pharmacokinetic parameters were compared between test and reference products from plasma concentration-time profile by using non-compartment analysis. The statistical comparison of C_max and AUC_0?t, AUC_t?∞ clearly indicated that no significant difference in two products of pioglitazone tablets in add-on subject study. The 90% confidence intervals for the mean ratio (test/reference) of C_max and AUC_0?t, AUC_t?∞ were within the Thailand Food and Drug Administration acceptance range. Based on the pharmacokinetic and statistical results of this study, we can conclude that Glubosil® is bioequivalent to Actos®, and that two products can be considered interchangeable in medical practice.     

Application of Simplex and Statistical Analysis for Correction of Pitting in Aqueous Film Coated Tablets

Pitting or pin hole formation is a tablet defect that is commonly observed in aqueous film coated tablets containing highly moisture-sensitive materials. It is generally believed that pitting is due to dissolution of soluble particles on the tablet surface when the tablet is overwetted during the coating process. An experiment was conducted to study the effects of spray rate and pan speed, the two important factors contributing to this condition. The data thus obtained were analyzed by using the simplex search procedure and the appropriate statistical methods. The levels of the two factors that minimized pitting were achieved as a result of the analysis.     

Assessment of the Thickness Variation and Surface Roughness of Aqueous Film Coated Tablets Using a Light-Section Microscope

Abstract

The Light-Section Microscope measures the thickness and surface roughness of transparent film coats without contacting them. It enables the determination of tablet film coat thickness at different regions on a tablet surface and analysis of coat thickness variation. Examination of aqueous film coated tablets using a Light-Section Microscope has shown that the coat application conditions can influence the film density and thickness, film thickness variation and film coat surface roughness. Coat application conditions which give rise to smoother surfaces are shown to produce more dense, thinner coats which may exhibit a more even thickness on smooth substrates but larger variations in film thickness on rough substrates. The potential for film thickness and surface roughness to vary at different positions on the substrate surface has also been demonstrated, with film coats tending to be smoother and thinner at the periphery of tablet faces.     

Optimization of Sotalol Floating and Bioadhesive Extended Release Tablet Formulations

Abstract

A novel extended release sotalol HC1 tablet formulation which possesses a unique combination of floatation and bioadhesion for prolonged residence in the stomach has been developed. Tablets were produced by direct compression. A two-factor factorial, central, composite Box-Wilson experimental design was employed to develop and optimize the tablet formulation containing 240 mg sotalol HC1. The ratio of two major bioadhesive agents, sodium carboxymethylcellulose (NaCMC) to hydroxypropylmethylcellulose (HPMC), and the ratio of two direct compressible diluents, ethylcellulose (EC) to crosspovidone, were used as formulation variables (independent variables) for optimizing tablets response parameters, such as dissolution bioadhesive capability, tablet density and required compression force for producing 6 Kg hardness tablets. The data were also analyzed by means of quadratic response surface model. Response surfaces were generated as a function of formulation variables. An optimum direct compression, bioadhesive and floating tablet formulation of sotalol HCl was achieved by considering the dissolution characteristic as primary objective and using required compression force, bioadhesive capability as constraints within the experimental region. The surface model was validated for accurate prediction of response characteristics.     

Optimization of Sotalol Floating and Bioadhesive Extended Release Tablet Formulations

A novel extended release sotalol HC1 tablet formulation which possesses a unique combination of floatation and bioadhesion for prolonged residence in the stomach has been developed. Tablets were produced by direct compression. A two-factor factorial, central, composite Box-Wilson experimental design was employed to develop and optimize the tablet formulation containing 240 mg sotalol HC1. The ratio of two major bioadhesive agents, sodium carboxymethylcellulose (NaCMC) to hydroxypropylmethylcellulose (HPMC), and the ratio of two direct compressible diluents, ethylcellulose (EC) to crosspovidone, were used as formulation variables (independent variables) for optimizing tablets response parameters, such as dissolution bioadhesive capability, tablet density and required compression force for producing 6 Kg hardness tablets. The data were also analyzed by means of quadratic response surface model. Response surfaces were generated as a function of formulation variables. An optimum direct compression, bioadhesive and floating tablet formulation of sotalol HCl was achieved by considering the dissolution characteristic as primary objective and using required compression force, bioadhesive capability as constraints within the experimental region. The surface model was validated for accurate prediction of response characteristics.     

Aqueous Gloss Solutions: Formula and Process Variables Effects on the Surface Texture of Film Coated Tablets

A specially designed spray box was constructed that allows spraying aqueous based film coating formulas under carefully controlled and reproducible conditions. The process variables studied included: spray distance, drying temperature, air cap, atomizing air pressure, and spray rate. Aqueous film coating gloss solutions were prepared using hydroxypropyl methyl cellulose. The viscosity grade, surface tension and concentration of polymer in solution were the formula variables studied. The surface texture of film coated tablets before and after spraying with the gloss solutions was analyzed with a stylus type surface roughness analyzer. The effect of the formula and process variables was also assessed by measurement of the tristimulus color difference obtained from colorimeter readings on the tablets, excluding versus including the specularly reflected light from the glossed surface. Within the ranges of the variables studied, the most significant effects on the surface texture were from the nozzle set up used and the spray distance.     

丙烯酸聚氨酯涂层在高湿热海洋大气环境中的老化行为

为研究丙烯酸聚氨酯涂层在高湿热海洋大气中的环境适应性及老化规律,在海南西沙永兴岛对其开展户外大气暴露试验。通过傅里叶红外光谱(FTIR)、X射线光电子能谱(XPS)、电化学阻抗谱(EIS)、扫描电子显微镜(SEM)等手段分析了不同老化时间下的涂层性能变化情况。结果表明:经过18个月的西沙永兴岛户外大气暴露试验,丙烯酸聚氨酯防护涂层主要宏观性能变化为粉化3级,推测氨基甲酸酯键(-NHCOO-)发生断裂,导致涂层致密性下降和综合防护性能降低。     

The Design and Performance of an Instrumentation System for Aqueous Film Coating in an Industrial Tablet Coating Machine

In recent years tablet coating has undergone several fundamental changes. The original sugar coating technique has been largely replaced by film coating processes using organic solvents. The organic solvents are now being replaced by water because of the development of suitable polymers, improvements in the coating process, and impending government legislation regulating the discharge of pollutants into the environment.

This change has resulted in increased interest in equipment designed for film coating based on cylindrical shaped side vented pans which allow the drying air to be drawn through the tablet bed. However, the process is complex and requires careful monitoring and control to ensure satisfactory results. The empirically derived conditions are not fundamentally understood and there are important differences in the operation     

Optimization of Direct Compression Tablet Formulations for Use in Tropical Countries

Abstract

With the aid of a combined mixture- and factorial- design, 2 standard tablet formulations were selected suitable for use in tropical countries. The formulations were based on native ingredients or ingredients that are available worldwide. The selection of the standard formulations was based on both the initial tablet properties of the formulations one day after preparation as well as the physical stability after storage under tropical conditions.

The selected formulations were evaluated by adding model drugs (diazepam, 2 mg per tablet or hydrochlorthiazide, 100 mg per tablet) and measuring tablet properties, not only one day after preparation, but also after storage under tropical conditions. Both selected tablet formulations were suitable standard formulations for tablets prepared by direct compression for use in tropical countries.