Yorinobu Yonezawa

Evaluation of Rapidly Disintegrating Tablets Prepared by a Direct Compression Method

To make rapidly disintegrating tablets with sufficient mechanical integrity as well as a pleasant taste, microcrystalline cellulose (MCC), Tablettose (TT), and crosslinked sodium carboxymethyl cellulose (Ac-di-sol) or erythritol (ET) were formulated. Tablets were made by a direct compression method (I). Tablet properties such as porosity, tensile strength, and disintegration time were determined. The tensile strength and disintegration time were selected as response variables, tablet porosity and parameters representing the characteristics of formulation were selected as controlling factors, and their relation was determined by the polynomial regression method. Response surface plots and contour plots of tablet tensile strength and disintegration time were also constructed. The optimum combination of tablet porosity and formulation was obtained by superimposing the contour diagrams of tablet tensile strength and disintegration time. Rapidly disintegrating tablets with durable structure and desirable taste could be prepared within the obtained optimum region.

Measurement of the Adhesive Force of Fine Particles on Tablet Surfaces and Method of Their Removal

The adhesion force of fine particles on the surface of tablets was measured by a centrifugal force and impact separation method. A Finededuster (FDD) was employed to remove fine particles from the tablet surface. The centrifugal force and impact separation method was suggested to be effective for measuring the adhesive forces between particles and the tablet surface, and effective disjoining force in the FDD could be estimated by comparison of the results obtained using these two methods. The FDD showed high removal efficiency regardless of how many tablets were processed at the same time. In either of these methods, critical particle size was about 10–20 μm, and larger particles were removed more efficiently. This critical particle size was similar to that observed for other mechanical properties of powders, such as angle of repose and flowability. We simulated particle residual percentage under various operation conditions by ANN (artificial neural network) analysis and multiple regression analysis. This simulation enabled us to predict how the efficiency of particle removal is affected by the interaction of the experimental and material factors.

Pharmaceutical evaluation of multipurpose excipients for direct compressed tablet manufacture : Comparisons of the capabilities of multipurpose excipients with those in general use

Recently, a novel type of multipurpose excipient (MPE) with high binding characteristics and high fluidity has been developed. In this study, the capabilities of MPEs (Ludipress and Microcelac) were compared with those of excipients in general use. Also, the effects on powder and tableting characteristics of the physical properties and contents of active ingredients were examined in tablets prepared with these MPEs by the direct compression method. Multipurpose excipients mixed with adjuvants such as fillers, binders, lubricants, disintegrants, and the like show superior fluidity and compressibility. Tablets containing very small amounts of highly active ingredients with little dispersion were prepared. However, with increases in active ingredient content, each of the physical properties was affected strongly by the properties of the active ingredient. Tablets with appropriate hardness and disintegration characteristics could be prepared by mixing of different types of MPEs.

Analysis of the Release Process of Phenylpropanolamine Hydrochloride from Ethylcellulose Matrix Granules III. Effects of the Dissolution Condition on the Release Process

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the entire release properties. As the first step, the dissolution test under various conditions is selected for the in vitro test, and usually the results are analyzed following Drug Approval and Licensing Procedures. In this test, 3 time points for each release ratio, such as 0.2-0.4, 0.4-0.6, and over 0.7, respectively, should be selected in advance. These are analyzed as to whether their values are inside or outside the prescribed aims at each time point. This method is very simple and useful but the details of the release properties can not be clarified or confirmed. The validity of the dissolution test in analysis using a combination of the square-root time law and cube-root law equations to understand all the drug release properties was confirmed by comparing the simulated value with that measured in the previous papers. Dissolution tests under various conditions affecting drug release properties in the human body were then examined, and the results were analyzed by both methods to identify their strengths and weaknesses. Hereafter, the control of pharmaceutical preparation, the manufacturing process, and understanding the drug release properties will be more efficient. It is considered that analysis using the combination of the square-root time law and cube-root law equations is very useful and efficient. The accuracy of predicting drug release properties in the human body was improved and clarified.

Preparation and evaluation of high drug content particles.

Abstract To determine how to prepare high drug content particles using a Wurster fluidized bed to determine realizing the miniaturization of solid dosage forms, aspirin was selected as the model drug and granulated without any additive. In this study, the emphasis was on evaluating the key operation factors of airflow rate and atomizing flow volume. The properties of the resulting particles, such as the average diameter, particle strength, appearance, and compressibility using different airflow rates and atomizing flow volumes, were investigated. Furthermore, detailed optimization of the operation conditions was conducted by artificial neural network (ANN) analysis. The relationship between the controlling factors (powder supplied, concentration of spray liquid, the amount of consumed spray liquid, and spray rate) and the response variables (product yield, median diameter, angle of repose, and degradation of aspirin) was investigated after evaluating the airflow rate and atomizing flow volume effects. The resulting granules under optimum operation conditions showed excellent physicochemical properties such as particle size uniformity, flowability, and compressibility.

Granulation of Acetaminophen by a Rotating Fluidized-Bed Granulator

The purpose of this research was to evaluate the use of a rotating fluidized-bed granulator to produce acetaminophen granules with sufficient binding force between particles and good plasticity in tablets. Ethenzamide and ascorbic acid were used to compare the relationship between granulation and the sample wetness. It was revealed that a blade rotation rate of 300 rpm, inlet air flow rate of 42 m3/hr, and spraying pressure of 1.5 kg/cm3 produced tablets with the best properties. The granule and tablet properties of ethenzamide and ascorbic acid were compared to those of acetaminophen. These compounds showed different wetting behaviors with water and different compression behaviors. With an increase in medicament content, tablet hardness increased except for the ascorbic acid formulation. Capping and sticking were observed in acetaminophen and in ascorbic acid, respectively, and acetaminophen and ethenzamide showed prolonged disintegration time.

Formation mechanism of wet-compressed rapidly disintegrating tablets containing a poorly water-soluble model drug

Rapidly disintegrating tablets are attracting attention as a dosage form that can be easily taken, even by elderly patients and children. In this study, rapidly disintegrating tablets were prepared by the wet-compression method and the formation mechanism of these tablets was evaluated. The tensile strength of the tablets increased with the amount of excipients (sugars) dissolved during the kneading process. More solid bridges were formed between drug particles and tablets with a greater tensile strength were obtained by increasing the amount of water and using more soluble sugars as excipients. When a swellable disintegrant was added, the porosity and the pore size of the tablets increased, probably because the disintegrant swelled by absorbing water during kneading, but shrank in the drying process after tableting. Thus, the use of a swellable disintegrant is considered to be important to induce the formation of a porous structure, which ensures rapid disintegration of the tablet. Therefore, optimization of the selection of the excipients (sugars) and disintegrant, and the amount of kneading water, was found to be necessary to prepare rapidly disintegrating tablets with a satisfactory tensile strength.

The effect of binder particle size on granule and tablet properties in high shear and extrusion granulation

Abstract We investigated the effects of binder particle size on high shear and extrusion granulation using the wet granulation method by evaluating the properties of granules and tablets. Ethenzamide was used as a model drug at a concentration of 1% with lactose/corn starch in a 7/3 mixture, with 3.5% hydroxypropylcellulose and 0.5% magnesiuu stearate as the standard formulation, as recommended by the Standard Formulation Research Association. Hydroxypropylcellulose, as the binder, was classified into three particle size grades with the sieving method and used by the powder and solution addition method. In conclusion, although an effect of differences in the binder particle size on the particle size and its distribution in high shear granulation granules was observed, it was not an important parameter in the product properties. Accordingly, it was thought that standardization of the binder particle size was useful to control the granule particle size.

Pharmaceutical manufacturing of crude drug powder prepared by the surface-modifying method

Crude drug powders are very useful for health and therapeutics, but these powders have various particle shapes and properties, leading to poor fluidity and strong adhesiveness and these properties make handling during processing of the powders and controlling the qualities of products difficult. The granulation of the crude drug seems to be an appropriate procedure to solve the problem. In our last study we examined pharmaceutical manufacture of crude drug powder using the dry compacting method, and we achieved our goal of tablet hardness of about 2.0 kg and disintegration time of less than 1,000 s. In this study, senna powder was chosen and we studied the surface-modifying method. We prepared tablets from surface modified senna powder, surface modified and dry granulated senna powder, and granules by unmodified and dry granulated senna powder and surface modifying agents added at the time of tableting. Their physical properties such as tablet hardness and disintegration time were evaluated. As a result, we achieved our goal of a more than 4.0 kg tablet hardness and less than 600 s disintegration time, when the tablet was made of granules of senna powder modified with 2% surface modification agents and dry granulated, and a disintegrant and more surface modification agents whose total content was 5% in the tablet, and tableting at 200 MPa.

Dissolution of Solid Dosage Form. III. Equations for the Dissolution of a Nondisintegrating Single Component Tablet under a Nonsink Condition

As equation was derived for the dissolution from the whole surface of a nondisintegrating single component tablet under a nonsink condition where the initial weight of a tablet is equal to the weight needed to saturate the solution. also, equations for several dissolution manners of the tablet under the nonsink condition were derived in the postulation of a dominant dissolution rate constant which determines the dissolution manner. The aplicability of these equations was examined by dissolution measurements with nondisintegrating single component tablets. Dissolution measurements of tablets prepared using the amount required to saturate the solution were conducted by masking their flat or side surface with adhesive tape in accordance with the conditions for the derivation of equations. These dissolution behaviors were treated by the use of derived equations to confirm the validity.Among the derived equations, dissolution from the whole surface of a tablet was expressed in the same form as the negative two-thirds law equation for particles, and a nondisintegrating single component tablet compressed by the use of stuitable amount was thought to behave like a single crystal. Also, equations, i.e., the negative two-thirds law and the negative square root law, thus derived were thought to be applicable for the dissolution of a nonspherical particle and crystal concerning the crystals habit and its dissolution property.