Effect of formulated ingredients on rapidly disintegrating oral tablets prepared by the crystalline transition method

The aim of this article was to determine the optimal ingredients for the rapidly disintegrating oral tablets prepared by the crystalline transition method (CT method). The effect of ingredients (diluent, active drug substance and amorphous sugar) on the characteristics of the tablets was investigated. The ingredients were compressed and the resultant tablets were stored under various conditions. The oral disintegration time of the tablet significantly depended on diluents, due to differences in the penetration of a small amount of water in the mouth and the viscous area formed inside the tablet. The oral disintegration time was 10-30 s for tablets with a tensile strength of approximately 1 MPa, when erythritol, mannitol or xylitol was used as the diluent. The increase in the tensile strength of tablets containing highly water-soluble active drug substances during storage was as large as that of tablets without active drug substances, while the increase in the tensile strength of tablets containing low water-soluble active drug substances was small. It was therefore found that highly water-soluble active drug substances were more suitable for the formulation prepared by the CT method than low water-soluble active drug substances. Irrespective of the type of amorphous sugar (amorphous sucrose, lactose or maltose) used, the porosity of tablets with 1 MPa of tensile strength was 30-40%, and their oral disintegration time was 10-20 s. The optimal ingredients for rapidly disintegrating oral tablets with reasonable tensile strength and disintegration time were therefore determined from these results.     

Pharmacokinetics of acetaminophen from rapidly disintegrating compressed tablet prepared using microcrystalline cellulose (PH-M-06) and spherical sugar granules

The aim of the present study was to evaluate the bioavailability of a drug from rapidly disintegrating tablets prepared using fine spherical crystalline cellulose (PH-M-06) and spherical sugar granules (Nonpareil, NP). Rapidly disintegrating tablets containing acetaminophen as the model drug in combination with a mixture of NP-108 (purified n-mannitol) and PH-M-06 were prepared. Plasma concentration profiles and pharmacokinetic parameters of acetaminophen in rabbits were investigated after oral administration of the prepared tablets. No significant difference in Cmax and AUC(0-infinity) of acetaminophen between rapidly disintegrating tablets and conventional tablets was observed after direct administration of these tablets into the stomach of rabbits. However, tmax (15 min) of acetaminophen from rapidly disintegrating tablets was significantly (p<0.05) shorter than that from conventional tablets (130 min). The same tmax was observed for rapidly disintegrating tablets and solution. When suitable excipients such as fine spherical microcrystalline cellulose (PH-M series) and spherical sugar granules (NP series) were used, rapidly disintegrating tablets could be prepared by the conventional direct compression method. According to the results of moment analysis, the mean residence time (MRT) obtained between both rapidly disintegrating and conventional tablets indicates that the mean absorption time (MAT) from these tablets is approximately 60 and 90 min, respectively. This difference in MAT between the two tablets may be caused by the difference in the sum of the mean dissolution time (MDT) and the mean disintegration time (MDIT) of these tablets. Rapidly disintegrating tablets allow rapid absorption of the drug compared with conventional tablets.     

Formulation and optimization of orally disintegrating tablets of sumatriptan succinate

The aims of the present research were to mask the intensely bitter taste of sumatriptan succinate and to formulate orally disintegrating tablets (ODTs) of the taste masked drug. Taste masking was performed by coating sumatriptan succinate with Eudragit EPO using spray drying technique. The resultant microspheres were evaluated for thermal analysis, yield, particle size, entrapment efficiency and in vitro taste masking. The tablets were formulated by mixing the taste masked microspheres with different types and concentrations of superdisintegrants and compressed using direct compression method followed by sublimation technique. The prepared tablets were evaluated for weight variation, thickness, hardness, friability, drug content, water content, in vitro disintegration time and in vitro drug release. All the tablet formulations disintegrated in vitro within 37-410 s. The optimized formulation containing 5% Kollidon CL-SF released more than 90% of the drug within 15 min and the release was comparable to that of commercial product (Suminat?). In human volunteers, the optimized formulation was found to have a pleasant taste and mouth feel and disintegrated in the oral cavity within 41 s. The optimized formulation was found to be stable and bioequivalent with Suminat?.     

Preparation and evaluation of tablets rapidly disintegrating in saliva containing bitter-taste-masked granules by the compression method.

The aim of this study was to prepare, using taste-masked granules, tablets which can rapidly disintegrate in saliva (rapidly disintegrating tablet), of drugs with bitter taste (pirenzepine HCl or oxybutynin HCl). The taste-masked granules were prepared using aminoalkyl methacrylate copolymers (Eudragit E-100) by the extrusion method. None of the drugs dissolved from the granules (% of dissolved, < 5%) even at 480 min at pH 6.8 in the dissolution test. However, the drugs dissolved rapidly in the medium at pH 1.2 in the dissolution test. Rapidly disintegrating tablets were prepared using the prepared taste-masked granules, and a mixture of excipients consisting of crystalline cellulose (Avicel PH-102) and low-substituted hydroxypropylcellulose (L-HPC, LH-11). The granules and excipients were mixed well (mixing ratio by weight, crystalline cellulose: L-HPC = 8:2) with 1% magnesium stearate, and subsequently compressed at 500-1500 kgf in a single-punch tableting machine. The prepared tablets (compressed at 500 kgf) containing the taste-masked granules have sufficient strength (the crushing strength: oxybutynin tablet, 3.5 kg; pirenzepine tablet, 2.2 kg), and a rapid disintegration time (within 20 s) was observed in the saliva of healthy volunteers. None of the volunteers felt any bitter taste after the disintegration of the tablet which contained the taste-masked granules. We confirmed that the rapidly disintegrating tablets can be prepared using these taste-masked granules and excipients which are commonly used in tablet preparation.     

Development and evaluation of a monolithic floating drug delivery system for acyclovir

Acyclovir (ACV), a model drug for this study, is one of the most effective drugs against viruses of the herpes group. Absorption of orally administered ACV is variable and incomplete, with a bioavailability of ca. 15-30%. The drug is absorbed in the duodenum after oral administration and hence, preparation of a floating drug delivery system (FDDS) for ACV may increase oral absorption of the drug. ACV matrix tablets (200?mg) containing an effervescent base (sodium bicarbonate and citric acid) and a binary combination of hydroxypropyl methylcellulose (HPMC) K4M with carbopol or sodium carboxymethyl cellulose (Na CMC) or polyvinylpyrrolidone (PVP) and/or sodium alginate were prepared by the direct compression method. The tablets were evaluated for physicochemical properties and in vitro floating ability (floating lag-time and duration), bioadhesiveness and drug release. The drug release studies were carried out in 0.1?N HCl (pH 1.2) at 37±0.5°C. At appropriate time intervals, samples were withdrawn and assayed spectrophotometrically at λ(max)=259?nm. The floating test showed tablets containing 15% effervescent base had a floating lag time of 10-30?s and a duration of floating time of 24?h. The formulations containing HPMC-PVP, HPMC-Na CMC, HPMC-carbopol, and HPMC-sodium alginate released about 60-90% of their drug content during a 12-h period. Increasing carbopol caused slower drug release. We concluded that the proposed tablets with 15% effervescent base, 20-30% HPMC, 30% Na CMC (and/or 20% PVP or 20% sodium alginate) showed good floating and drug release properties in vitro, and should be considered as FDDS for ACV.     

Preparation and evaluation of orally rapidly disintegrating tablets containing taste-masked particles using one-step dry-coated tablets technology

In this study, in order to address the problems with manufacturing orally rapidly disintegrating tablets (ODT) containing functional (taste masking or controlled release) coated particles, such as the low compactability of coated particles and the rupture of coated membrane during compression, a novel ODT containing taste-masked coated particles (TMP) in the center of the tablets were prepared using one-step dry-coated tablets (OSDrC) technology. As a reference, physical-mixture tablets (PM) were prepared by a conventional tableting method, and the properties of the tablets and the effect of compression on the characteristics of TMP were evaluated. OSDrC was found to have higher tensile strength and far lower friability than PM, but the oral disintegration time of OSDrC is slightly longer than that of PM following high compression pressure. Consequently, OSDrC approaches the target tablet properties of ODT, whereas PM does not. The deformation of TMP in OSDrC due to compression is slight, and the release rate of acetaminophen (AAP) from OSDrC is the same as from TMP. However, TMP on the surface of PM are considerably deformed, and the release rate of AAP from PM is faster than from TMP. These findings suggest that OSDrC technology is a useful approach for preparing ODT containing functional coated particles. Furthermore, we demonstrate that the elastic recovery of tablets can affect differences in the properties of OSDrC, PM and placebo tablets (PC).     

Effect of moisture on impact toughness of sugar-coated tablets manufactured by the dusting method

The purpose of this study was to clarify the effect of moisture on the impact toughness of sugar-coated tablets manufactured by the dusting method. We demonstrated that moisture plays an important role in the impact toughness of sugar-coated tablets. Moisturizing the sugar-coating layer resulted in enhancement of impact toughness of sugar-coated tablets, while reducing moisture in the sugar-coating layer resulted in weakening of the impact toughness. This was due to the characteristics of sucrose, the main ingredient of the sugar-coating layer, which is a soft and non-fragile material at high moisture levels, but hard and fragile at low moisture levels. We also demonstrated that friability as an indicator of impact toughness changed with time, and friability should be measured at 14 d after manufacture. This is due to moisture movement from outer sugar-coating layer into the inner sugar-coated tablets. Incorporating microcrystalline cellulose (MCC) in the subcoating layer resulted in sugar-coating layers with high resistance against impact even though moisture content of sugar-coated tablets was low. We confirmed the high impact toughness of the sugar-coated tablets with MCC whose moisture content was low from the results of both free fall and friability tests. We suggest that the dusting method using dusting powder containing MCC is a useful method for the production of sugar-coated tablets containing moisture sensitive drugs.     

Spray dried excipient base: a novel technique for the formulation of orally disintegrating tablets

Orally disintegrating tablets (ODT) are gaining popularity over conventional tablets due to their convenience in administration and suitability for patients having dysphagia. Moreover no water is required for swallowing the tablets and hence suitable for geriatric, pediatric and traveling patients. The purpose of this study is to assess the suitability of spray dried excipient base in the formulation of ODTs of Valdecoxib (low aqueous solubility) and Metoclopramide (high aqueous solubility). Spray dried excipient base was prepared using Scientech spray drier. Super disintegrants (such as Ac-Di-Sol, Kollidon CL, sodium starch glycolate), diluent (mannitol) alongwith sweetening agent (aspartame) were used in the formulation of tablets. The tablets were evaluated for hardness, friability, water absorption ratio, disintegration time (DT) and in vitro drug release. Using the same excipients, the tablets were prepared by direct compression and were evaluated in the similar way. Maximum drug release and minimum DT were observed with Kollidon CL excipient base as compared to tablets prepared by direct compression, showing the superiority of the spray dried excipient base technique over direct compression technique.     

Formulation study for orally disintegrating tablet using partly pregelatinized starch binder

In this study, we aimed to design orally disintegrating tablets by employing a formulation design approach that enables the production of such tablets in the same facilities used for the production of solid dosage forms on an industrial scale. First, we examined the relationships between the types of binders used in the tablets and the properties of orally disintegrating tablets prepared by the wet granulation method. Results revealed that partly pregelatinized starch is a relatively suitable binder for orally disintegrating tablets as it also serves as a disintegrant. Next, we employed a central composite design for 2 factors, namely, corn starch and partly pregelatinized starch, in order to design granules suited for orally disintegrating tablets composed of D-mannitol, corn starch or partly pregelatinized starch. The effects of these 2 factors on 3 types of responses, namely, 50% granule size, compressing index and disintegrating index, were analyzed with a software package, and responses to changes in the factors were predicted. This study investigated the effects of binder type and binder content in orally disintegrating tablets, and provided evidence that the binder exerts a strong influence on tablet properties, and is therefore an important component of orally disintegrating tablets.     

Preparation of rapidly disintegrating tablets containing itraconazole solid dispersions

The disintegratability of tablets prepared from two types of solid dispersions containing the water-soluble polymer TC-5 and the enteric polymer HP-55 as an excipient were compared. The disintegratability was better in the tablets of solid dispersions containing non-water-soluble HP-55 than those containing TC-5. In consideration of the dissolubility of solid dispersions containing HP-55, the mean diameter of the solid dispersion (coating powder) must be controlled to 120 microm or less, but as this markedly increases the adhesion/aggregation tendency of the particles (angle of repose: 47 degrees ), control of the adhesion/aggregation tendency emerged as another problem. Therefore, surface-modification was performed in a high-speed agitating granulator using 0.1% light anhydrous silicic acid as a surface modifier, and marked improvement in the flowability was observed. This made continuous tableting using a rotary tablet machine possible even with the poorly flowable solid dispersions. Also, in tableting of the solid dispersions, no recrystallization of amorphous itraconazole by the tableting pressure was observed, and the tablets maintained satisfactory dissolubility. Moreover, it was possible to obtain the rapidly disintegrating tablets with very satisfactory properties, i.e., a tablet hardness of 30 N or higher and a disintegration time of 30 s or less, by the addition of croscarmellose as a disintegrant at 2% to the surface-modified solid dispersion and selection of the tableting pressure at 4.5 kN.     

Studies of rapidly disintegrating tablets in the oral cavity using co-ground mixtures of mannitol with crospovidone

We attempted the development of rapid oral disintegration tablets by direct compression using co-ground mixture of D-mannitol and crospovidone. The co-ground mixture was prepared with a vibration rod mill. The tablets were formed by compression using a single punch-tableting machine after addition of the co-ground mixture to non-ground D-mannitol, crospovidone and magnesium stearate. Regarding the properties of tablets, hardness and the time of disintegration were measured. The particle diameter and specific surface area of the co-ground mixture were measured. The tablets manufactured from a physical mixture of 30% (w/w) co-ground mixture of D-mannitol and crospovidone (mixed ratio 9 :1) with 65.5% (w/w) of non-ground mannitol, 4% (w/w) of crospovidone, and 0.5% (w/w) of magnesium stearate had good properties for rapidly disintegrating tablets in the oral cavity. They showed the hardness of 4.9 kg and disintegration time of 33 s. We found that adding co-ground mixture of D-mannitol and crospovidone is useful in enhancing hardness of the tablets that could not be achieved by addition of their individually ground mixture. The improvement in the hardness of the tablets was also observed when other saccharides and disintegrants were used. This method was proved to be applicable in the manufacture of tables of ascorbic acid, a water-soluble drug and nifedipine, a slightly water soluble drug; and the dissolution rate of nifedipine from the tablets in water was remarkably improved. The particle sizes of D-mannitol in the co-ground mixture were smaller than that of the individually ground mixture, resulting in a larger specific surface area of the co-ground mixture than that of the individually ground mixture. Therefore, it was presumed that crospovidone acted as a grinding assistant for D-mannitol in the co-grinding process, enhancing the hardness of tablets by increasing the contact area among powder particles.     

Combined use of cyclodextrins and hydroxypropylmethylcellulose stearoxy ether (Sangelose®) for the preparation of orally disintegrating tablets of type-2 antidiabetes agent glimepiride

Despite recent advances in the formulation of orally disintegrating tablets (ODTs), the efforts to enhance the swallowing of the drug after disintegration have been limited. In this study, the feasibility of the combined use of cyclodextrins (CyDs) and a functional drug carrier, hydroxypropylmethylcellulose stearoxy ether (Sangelose^®) was investigated to improve usability of ODTs. Glimepiride, a potent third generation hypoglycemic agent for type 2 diabetes was used as a model drug, because it is poorly water-soluble and elimination half life is fairly short. The direct compression method was employed for the preparation of glimepiride tablets, containing CyDs and Sangelose^®, and various characteristics of the tablets were examined. In the cases of α-CyD and β-CyD, a short disintegration time with an appropriate hardness was obtained, complying with ODT criteria. On the other hand, γ-CyD, HP-β-CyD and HB-β-CyD increased in the hardness and disintegration time of the tablets. The rheological evaluation revealed that CyDs, except γ-CyD, significantly reduced the viscosity of the fluids after disintegration of the tablets, suggesting an ease of swallowing. This was ascribable to the complexation of the hydrophobic stearoyl moiety of Sangelose^® with CyDs after dissolution, leading to the inhibition of the polymer–polymer interaction of Sangelose^® and to the decrease in viscosity of the solution. The interaction of glimepiride with α- and β-CyDs was studied by the solubility method, demonstrating that glimepiride formed water-soluble complexes with these CyDs. Results obtained here suggested that α-CyD and β-CyD can be particularly useful for the Sangelose^®-based ODT formulation, compared to γ-CyD, HP-β-CyD and HB-β-CyD, because of the short disintegration time of the tablets containing α-CyD and β-CyD, their shear-thinning effect on Sangelose^® solutions and their solubility enhancing effect on the drug.     

Manufacturing and Assessing the New Orally Disintegrating Tablets,Containing Nimodipine-hydroxypropyl-β-cyclodextrin and Nimodipine-methyl-β-cyclodextrin Inclusion Complexes

The aim of the present study was to manufacture new orally disintegrating tablets containing nimodipine–hydroxypropyl-β-cyclodextrin and nimodipine–methyl-β-cyclodextrin inclusion complexes. For obtaining a better quality of the manufactured tablets, three methods of the preparation of inclusion complexes, in a 1:1 molar ratio, were used comparatively; namely, a solid-state kneading method and two liquid state coprecipitation and lyophilization techniques. The physical and chemical properties of the obtained inclusion complexes, as well as their physical mixtures, were investigated using Fourier transformed infrared spectroscopy, scanning electron microscopy, X-ray diffraction analyses, and differential scanning calorimetry. The results showed that the lyophilization method can be successfully used for a better complexation. Finally, the formulation and precompression studies for tablets for oral dispersion, containing Nim–HP-β-CD and Nim–Me-β-CD inclusion complexes, were successfully assessed.     

Properties of gastroretentive sustained release tablets prepared by combination of melt/sublimation actions of L-menthol and penetration of molten polymers into tablets

A novel floating sustained release tablet having a cavity in the center was developed by utilizing the physicochemical properties of L-menthol and the penetration of molten hydrophobic polymer into tablets. A dry-coated tablet containing famotidine as a model drug in outer layer was prepared with a L-menthol core by direct compression. The tablet was placed in an oven at 80°C to remove the L-menthol core from tablet. The resulting tablet was then immersed in the molten hydrophobic polymers at 90°C. The buoyancy and drug release properties of tablets were investigated using United States Pharmacopeia (USP) 32 Apparatus 2 (paddle 100 rpm) and 900 ml of 0.01 N HCl. The L-menthol core in tablets disappeared completely through pathways in the outer layer with no drug outflows when placed in an oven for 90 min, resulting in a formation of a hollow tablet. The hollow tablets floated on the dissolution media for a short time and the drug release was rapid due to the disintegration of tablet. When the hollow tablets were immersed in molten hydrophobic polymers for 1 min, the rapid drug release was drastically retarded due to a formation of wax matrices within the shell of tablets and the tablets floated on the media for at least 6 h. When Lubri wax? was used as a polymer, the tablets showed the slowest sustained release. On the other hand, faster sustained release properties were obtained by using glyceryl monostearate (GMS) due to its low hydrophobic nature. The results obtained in this study suggested that the drug release rate from floating tablets could be controlled by both the choice of hydrophobic polymer and the combined use of hydrophobic polymers.     

Evaluation of the disintegration time of rapidly disintegrating tablets via a novel method utilizing a CCD camera

Many kinds of rapidly disintegrating or oral disintegrating tablets (RDT) have been developed to improve the ease of tablet administration, especially for elderly and pediatric patients. In these cases, knowledge regarding disintegration behavior appears important with respect to the development of such a novel tablet. Ordinary disintegration testing, such as the Japanese Pharmacopoeia (JP) method, faces limitations with respect to the evaluation of rapid disintegration due to strong agitation. Therefore, we have developed a novel apparatus and method to determine the dissolution of the RDT. The novel device consists of a disintegrating bath and CCD camera interfaced with a personal computer equipped with motion capture and image analysis software. A newly developed RDT containing various types of binder was evaluated with this protocol. In this method, disintegration occurs in a mildly agitated medium, which allows differentiation of minor distinctions among RDTs of different formulations. Simultaneously, we were also able to detect qualitative information, i.e., morphological changes in the tablet during disintegration. This method is useful for the evaluation of the disintegration of RDT during pharmaceutical development, and also for quality control during production.     

Formulation Development of Mirtazapine Liquisolid Compacts: Optimization Using Central Composite Design

Mirtazapine is a tetracyclic anti-depressant with poor water solubility. The aim of this study was to improve the dissolution rate of mirtazapine by delivering the drug as a liquisolid compact. Central composite design (CCD) was employed for the preparation of mirtazapine liquisolid compacts. In this, the impacts of two independent factors, i.e., excipient ratio (carrier:coating) and different drug concentration on the response of liquisolid system were optimized. Liquisolid compacts were prepared using propylene glycol as a solvent, microcrystalline cellulose as a carrier, and silicon dioxide (Aerosil) as the coating material. The crystallinity of the formulated drug and the interactions between the excipients were examined using X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR), respectively. The dissolution study for the liquisolid compact was carried out as per FDA guidelines. The results showed loss of crystallinity of the mirtazapine in the formulation and was completely solubilized in non-volatile solvent and equally dispersed throughout the powder system. Moreover, drug dissolution was found to be higher in liquisolid compacts than the direct compressed conventional tablets (of mirtazapine). The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like mirtazapine.     

Evaluation of cyclodextrin polymer as a disintegrating agent

Cyclodextrin polymer was compared to other well known disintegrants concerning the swelling properties /water uptake, moisture uptake, hydration capacity, sedimentation volume in water/. Its high disintegrating effect was proved in directly compressed tablets as well as in tablets made by wet granulation. A remarkable improvement in tablet properties was observed. Not only the disintegration of tablets and the dissolution of the drug was accelerated but also the hardness increased when CDP was used as disintegrant.     

Formulation approach for nicorandil pulsatile release tablet

The purpose of this study was to obtain a nicorandil pulsatile release tablet that has a well-regulated release lag time. When nicorandil is used as an antiangina drug, administration time control is important. A pulsatile release tablet is one of the effective approaches to modified release to reduce daily administration frequency. In this study, a pulsatile release tablet of nicorandil was formulated by fumaric acid dry coating around the core tablet including nicorandil. The model tablets, which had different content ratios of excipients in the dry-coating layer, were characterized by a dissolution test. The results showed that the release lag time was generated with fast release profiles. Various lag time controls of tablets were achieved, from 60 to 310 min on average, by variation of outer layer composition. From an analysis of the relation between lag times and outer layer composition, the key ingredient for prolongation of lag time was found to be fumaric acid. To analyze the lag time generation mechanism, water penetration for tablet was measured. The results indicated that the penetration depth was proportionate to the square root of time and the lag time formation mechanism was simple water penetration through the matrix of fumaric acid to the tablet core. The results also showed that the Washburn equation could be used to design the lag time of the pulsatile release tablet in this study. In conclusion, novel release control technology using fumaric acid was appropriate to obtain a nicorandil pulsatile release tablet that has well regulated lag time.     

Development of fast disintegrating compressed tablets using amino acid as disintegration accelerator: evaluation of wetting and disintegration of tablet on the basis of surface free energy

A fast disintegrating compressed tablet was formulated using amino acids, such as L-lysine HCl, L-alanine, glycine and L-tyrosine as disintegration accelerator. The tablets having the hardness of about 4 kgf were prepared and the effect of amino acids on the wetting time and disintegration time in the oral cavity of tablets was examined on the basis of surface free energy of amino acids. The wetting time of the tablets increased in the order of L-lysine HCl, L-alanine, glycine and L-tyrosine, whereas the disintegration time in the oral cavity of the tablets increased in the order of L-alanine, glycine, L-lysine HCl and L-tyrosine. These behaviors were well analyzed by the introduction of surface free energy. When the polar component of amino acid was large value or the dispersion component was small value, faster wetting of tablet was observed. When the dispersion component of amino acid was large value or the dispersion component was small value, faster disintegration of tablet was observed, expect of L-tyrosine tablet. The fast disintegration of tablets was explained by the theory presented by Matsumaru.     

Preparation of rapidly disintegrating tablet using new types of microcrystalline cellulose (PH-M series) and low substituted-hydroxypropylcellulose or spherical sugar granules by direct compression method

To decrease the sensation of roughness when a tablet, which is rapidly disintegrated by saliva (rapidly disintegrating tablet), is orally taken, we prepared rapidly disintegrating tablets using microcrystalline cellulose (Avicel PH-M series), a new type of pharmaceutical excipient that is spherical and has a very small particle size (particle size, 7-32 microm), instead of conventional microcrystalline cellulose (PH-102) used in the formulation of tablets containing acetaminophen or ascorbic acid as model drugs for tableting study. Tablets (200 mg) prepared using spherical microcrystalline cellulose, PH-M-06, with the smallest particle size (mean value, 7 microm) had sufficient crushing tolerance (approximately, 8 kg) and were very rapidly, disintegrated (within 15 s) when the mixing ratio of PH-M-06 to low-substituted hydroxypropylcellulose (L-HPC) was 9:1. Sensory evaluation by volunteers showed that PH-M-06 was superior to PH-102 in terms of the feeling of roughness in the mouth. Consequently, it was found that particle size is an important factor for tablet preparation using microcrystalline cellulose. It is possible to prepare drugs such as acetaminophen and ascorbic acid (concentration of approximately 50%) in the tablet form using PH-NM-06 in combination with L-HPC as a good disintegrant at a low compression force (1-6 kN). To solve the problem of poor fluidity in the preparation of these tablets, we investigated the use of spherical sugar granules (Nonpareil, NP-101 (sucrose and starch, composition ratio of 7:3), NP-103 (purified sucrose), NP-107 (purified lactose) and NP-108 (purified D-mannitol)). Rapidly disintegrating tablets can be prepared by the direct compression method when suitable excipients such as fine microcrystalline cellulose (PH-M-06) and spherical sugar granules (NP) are used.