Combination preparations play an important role in clinical treatment because of their better and wider curative effects or weaker side effects. However, the existence of incompatibility between active ingredients or between active ingredients and excipients presents a serious obstacle in the preparation of such combination solid dosage forms. In this study, aspirin and ranitidine hydrochloride were used as the model drugs, between which there existed an interaction. Aspirin was granulated by a Wurster fluidized bed and the operation condition was optimized using the ANN (Artificial Neutral Network) analysis. On the other hand, ranitidine hydrochloride was layered to the core particle with PEG4000 as a carrier using a high-speed agitation mixer, and the factors affecting the ranitidine chloride content and layering particle yield such as the amount of PEG4000 used, core particles and agitating rate, agitating time and melting temperature were investigated in detail. Optimized aspirin granules and ranitidine layering particles were mixed and compressed into tablets. The hardness, content uniformity, dissolution and stability of the tablet were evaluated.

We investigated the content and blend uniformity of drugs in granules and tablets made by the fluidized bed-granulation method using three active ingredients, ascorbic acid, ethenzamide and acetaminophen, as model drugs. They were used at concentrations of 0.1% and 1%, with lactose/corn starch in a 7/3 mixture and hydroxypropylcellulose as the standard formulation, as recommended by the Standard Formulation Research Association. Consequently, good content uniformity was confirmed for all three model drugs under suitable manufacturing conditions in this study. However, care must be taken when the particles of active ingredients are fine, because the loss of drugs by passing through the bag-filter or adhering to the wall of the granulator during the granulation process is possible.

Novel 4-fluid nozzle spray driers have a unique nozzle which has two liquid passages and two gas passages. We spotlighted a novel atomizing principle of the 4-fluid nozzle spray drier and attempted to prepare particles for dry powder inhalation (DPI) using Sodium Salicylate (SS) as a model drug. The effect of operating condition for spraying, such as inlet temperature, drug concentration of spray solution and feed rate on the powder properties of SS particles, was studied. An vitro pulmonary inhalation study of SS particles was performed with a cascade impactor. More than 90% of the SS particles were within the diameter range of 0.5-7.0 μm, which is called the respirable fraction (RF). It was feasible to control the diameter of the SS particles within the RF range by varying the drug concentration of the spray solution. Spray-dried SS particles showed a high capsule-emitted percent and high drug delivery percent for RF as compared to jet-milled SS particles. Furthermore, smaller spray-dried SS particles showed a higher drug delivery point for RF.

The paddle rotation speed of 50 rpm has widely been accepted for dissolution tests since the implementation of Guidelines for Bioequivalence Studies in Japan. However, there have been a limited number of systematic studies reporting the effect of disintegrants on drug dissolution evaluated at 50 rpm. In this study, we compared the effect of three disintegrants, croscarmellose sodium (CCS), carboxymethylcellulose (CMC) and cros povidone (CP), on the disintegration and dissolution rates of ethenzamide, a poorly water soluble model drug, from tablets. The disintegrants were formulated in the tablets so that more than 85% of the drug would be dissolved in 30 to 60 min by the dissolution test at 50 rpm. It is worthwhile examining the effect of disintegrants on the tablets with such a dissolution rate because it is generally recognized that it is not easy to prepare a tablet bioequivalent to a standard tablet with such a dissolution rate. CCS and CMC increased the dissolution rate at a content of 1% or less. CP showed no effect as a disintegrant at this content due to interaction with magnesium stearate. However, its effect on the dissolution rate was the largest among the three disintegrants at the concentration of more than 1%. The increase in dissolution rate was well correlated with increase in the water absorption rate by the tablets with disintegrants.