Suitability of κ-carrageenan pellets for the formulation of multiparticulate tablets with modified release

κ-Carrageenan is a novel pelletisation aid with high formulation robustness and quick disintegration leading to fast drug release unlike the matrix-like release from non-disintegrating microcrystalline cellulose pellets. Compression of pellets into tablets is cost effective. The feasibility of formulating multiparticulate tablets with coated κ-carrageenan pellets was investigated. Pellets containing a highly soluble drug in acid, namely bisacodyl and κ-carrageenan or MCC as pelletisation aid were prepared, enteric coated with a mixture of Kollicoat(?) MAE 30 DP and Eudragit(?) NE 30 D and compressed using silicified microcrystalline cellulose as embedding powder. The effect of coating level, type of pellet core, compression force and punch configurations on drug release were studied. A sufficient coating thickness for κ-carrageenan pellets was necessary to obtain multiparticulate tablets with adequate resistance in the acid stage regardless of the compression pressure used. While κ-carrageenan pellets and their tablets released over 80% of the drug during the neutral stage only about 20-24% was released from MCC pellets and their tablets. The type of punches used (oblong or round) did not significantly influence the drug release from the prepared tablets. Moreover, sufficient prolonged release properties were obtained with κ-carrageenan pellets containing theophylline as a model drug and coated with Kollicoat(?) SR 30 D using Kollicoat(?) IR as pore former. A lower coating level and higher amount of pore former were needed in case of theophylline pellets formulated with MCC as pelletisation aid. The sustained release properties of both coated pellet formulations were maintained after compression at different compression pressures.     

Comparison of the compression characteristics between new one-step dry-coated tablets (OSDRC) and dry-coated tablets (DC)

One-step dry-coated tablets (OSDRC) were prepared using materials which are generally used in pharmaceutical tablets. The radial tensile strength of OSDRC was measured for various compression pressures and core porosities before the final compression to compare with that of conventional dry-coated tablets (DC). Furthermore, stress relaxation in the compression process was investigated. Radial tensile strength and stress relaxation profiles of OSDRC were the same as those of conventional DC. X-ray computerized tomography (CT) of the tablets showed that the density distribution of both tablets was also the same. Thus, we concluded that OSDRC and conventional DC have the same compression characteristics and physical properties. The OSDRC-system was executed by the use of upper and lower punches, which had a double structure, a center punch, and an outer punch surrounding the center punch. The OSDRC process consists of three compressions to make the lower-outer layer (1st-outer layer), the core, and the whole tablet including the upper-outer and side-outer layers (2nd-outer layer). At first, the powder for the 1st-outer layer fills a space, which is made by the lower-center punch and lower-outer punch, and is pre-compressed by the upper-center punch. Then, while the upper-center punch pushes the pre-compressed 1st-outer layer, the lower-center punch is slid down. The upper-center punch is then pulled away to make a space, which is filled with the powder for the core. This is then pre-compressed by the upper-center punch. Finally, the lower-outer punch is slid downward and the powder for the 2nd-outer layer fills and surrounds the pre-compressed core/1st-outer layer completely. The core/1st-outer layer and the 2nd-outer layer complex is then compressed by the upper and lower punches in which the center punches are unified with the outer punches, respectively. This system can be assembled onto the turn table of a rotary tableting machine, and can make a dry-coated tablet in a single turn.     

Compaction, compression and drug release properties of diclofenac sodium and ibuprofen pellets comprising xanthan gum as a sustained release agent

Compaction and compression of xanthan gum pellets were evaluated and drug release from tablets made of pellets was characterised. Two types of pellets were prepared by extrusion-spheronisation. Formulations included xanthan gum, at 16% (w/w), diclofenac sodium or ibuprofen, at 10% (w/w), among other excipients. An amount of 500 mg of pellets fraction 1000-1400 microm were compacted in a single punch press at maximum punch pressure of 125 MPa using flat-faced punches (diameter of 1.00 cm). Physical properties of pellets and tablets were analysed. Laser profilometry analysis and scanning electron microscopy of the upper surface and the surface of fracture of tablets revealed that particles remained as coherent individual units after compression process. Pellets were flatted in the same direction of the applied stress evidencing a lost of the original curvature of the spherical unit. Pellets showed close compressibility degrees (49.9% for pellets comprising diclofenac sodium and 48.5% for pellets comprising ibuprofen). Xanthan gum pellets comprising diclofenac sodium experienced a reduction of 65.5% of their original sphericity while those comprising ibuprofen lost 49.6% of the original porosity. Permanent deformation and densification were the relevant mechanisms of compression. Fragmentation was regarded as non-existent. The release of the model drug from both type of tablets revealed different behaviours. Tablets made of pellets comprising ibuprofen released the model drug in a bimodal fashion and the release behaviour was characterised as Case II transport mechanism (release exponent of 0.93). On the other hand, the release behaviour of diclofenac sodium from tablets made of pellets was anomalous (release exponent of 0.70). For the latter case, drug diffusion and erosion were competing mechanisms of drug release.     

Compressibility of floating pellets with verapamil hydrochloride coated with dispersion Kollicoat SR 30 D.

The purpose of this study was to work out a method of compression of floating pellets with verapamil hydrochloride (VH) in a dose of 40 mg. It was assumed that this form should reside in the stomach floating for several hours and gradually release the drug in a controlled way. Compression of pellets into tablets, being a modern technological process, is much more perfect than enclosing them in a hard gelatin capsule. Kollicoat SR 30 D was selected for coating. In experiments three plasticizers were examined-propylene glycol, triethyl citrate and dibuthyl sebecate (all at concentration of 10%). It was found that VH release from pellets coated by the films of the same thickness (70 microm), however, containing plasticizers is considerably different. Pellets were prepared by wet granulation of powder mixture, spheronization of the granulated mass and coating of the cores with a sustained release film. Two kinds of cellulose, microcrystalline and powdered, and sodium hydrocarbonate were the main components of pellet core. Proper pellet coating film thickness, ensuring obtaining desirable VH release profile and flotation effect, was defined. X compositions of tablets with pellets were examined in order to obtain formulation, from which VH release would mostly approximate pellets before compressing. The best formulation was evaluated taking into account the effect of compression force an tablet hardness and friability, and pellet agglomeration and flotation. Tablet cross-section photographs were taken confirming necessary coating film thickness preventing their deformation caused by compressing into tablets.     

Compaction, compression and drug release characteristics of xanthan gum pellets of different compositions.

Compaction and compression of xanthan gum (XG) pellets were evaluated and drug release from tablets made of pellets was characterised. Three formulations were prepared by extrusion-spheronisation and included, among other excipients, diclofenac sodium (Dic Na), at 10% (w/w); xanthan gum, at 16% (w/w); and one of three different fillers (lactose monohydrated (LAC), tribasic calcium phosphate (TCP) and beta-cyclodextrin (beta-CD)), at 16% (w/w). Five hundred milligrams of pellets (fraction 1000-1400microm) were compacted in a single punch press at maximum punch pressure of 125MPa using flat-faced punches (diameter of 1.00cm). Physical properties of pellets and tablets were analysed. Dissolution was performed according to the USP paddle method. Pellets showed close compressibility degrees (49.27% LAC; 51.32% TCP; and 50.48% beta-CD) but densified differently (3.57% LAC; 14.84% TCP; 3.26% beta-CD). Permanent deformation and densification were the relevant mechanisms of compression. Fragmentation was regarded as non-existent. The release behaviour of tablets made of pellets comprising LAC or beta-CD was anomalous having diffusional exponent (n) values of 0.706 and 0.625, respectively. Drug diffusion and erosion were competing mechanisms of drug release from those tablets.     

Formulation and evaluation of omeprazole tablets for duodenal ulcer

Omeprazole pellets containing mucoadhesive tablets were developed by direct punch method. Three mucoadhesive polymers namely hydroxypropylemethylcellulose K4M, sodium carboxy methylcellulose, carbopol-934P and ethyl cellulose were used for preparation of tablets which intended for prolong action may be due to the attachment with intestinal mucosa for relief from active duodenal ulcer. Mucoadhesive tablets were coated with respective polymer and coated with Eudragit L100 to fabricate enteric coated tablets. The prepared tablets were evaluated for different physical parameters and dissolution study were performed in three dissolution mediums like 0.1N hydrochloric acid for 2h, pH 6.5 and pH 7.8 phosphate buffer solution for 12hr. Sodium carboxymethylcellulose showed above 95% release within 10 h where as carbopol-934P showed slow release about 88% to 92% over a period of 12 h. having excellent mucoadhesive strength but ethyl cellulose containing tablets showed less than 65% release. The release mechanism of all formulation was diffusion controlled confirmed from Higuchi's plot. Thus, the present study concluded that, carbopol-934P containing mucoadhesive tablets of omeprazole pellets can be used for local action in the ulcer disease as well as for oral controlled release drug delivery.     

Non-Destructive Evaluation of Polymer Coating Structures on Pharmaceutical Pellets Using Full-Field Optical Coherence Tomography

Full-field optical coherence tomography (FF-OCT) using a conventional light-emitting diode and a complementary metal-oxide semiconductor camera has been developed for characterising coatings on small pellet samples. A set ofen-faceimages covering an area of 700 × 700 μm²was taken over a depth range of 166 μm. The three-dimensional structural information, such as the coating thickness and uniformity, was subsequently obtained by analysis of the recordeden-faceimages. Drug-loaded pharmaceutical sustained-release pellets with two coating layers and of a sub-millimetre diameter were studied to demonstrate the usefulness of the developed system. We have shown that both coatings can be clearly resolved and the thickness was determined to be 40 and 50 μm for the outer and inner coating layers, respectively. It was also found that the outer coating layer is relatively uniform, whereas the inner coating layer has many particle-like features. X-ray computed microtomography measurements carried out on the same pellet sample confirmed all these findings. The presented FF-OCT approach is inexpensive and has better spatial resolution compared with other non-destructive analysis techniques such as terahertz pulsed imaging, and is thus considered advantageous for the quantitative analysis of thin coatings on small pellet samples.     

Development of disintegrating multiple-unit tablets on a high-speed rotary tablet press.

Enteric coated bisacodyl pellets were compressed into divisible disintegrating tablets on a high speed rotary tablet press and investigated for pellet damages. The degree of pellet damages was examined via the bisacodyl dissolution during the acid treatment of' the drug release test for enteric coated articles according to USP 23. The damages depended on the type of filler-binder used and settings of the tablet press. Avicel PH 101 proved to be the most suitable filler-binder, effecting homogeneous distribution of the pellets within the tablets, as could be shown by image analysis of coloured pellets. The speed of the tablet press had noo influence on the pellet damages using Avicel PH 101 as a filler-binder, however, tablets containing 70% (w/w) of coated pellets did not fulfil the requirements of USP 23, despite optimum elasticity and coating thickness of a new Eudragit FS 30 D coating. Reducing the proportion of pellets to 60% per tablet, less than 10% of bisacodyl were released within 2 h during acid treatment thus fulfilling the requirements of the USP 23.     

Advanced formulation design of venlafaxine hydrochloride coated and triple-layer tablets containing hypromellose

The purpose of this research work was to develop venlafaxine hydrochloride-coated and layered matrix tablets using hypromellose adopting wet granulation technique. The granules and the tablets were characterized. The monolithic tablets were coated with different ratios of ethyl cellulose and hypromellose. The in vitro dissolution study was performed in distilled water. In the layered tablets, the middle layer containing drug was covered with barrier layers containing high viscosity grade hypromellose. Simplex lattice design was used for formulating the layered tablets. The dissolution study of the optimized batches and a reference product was carried out in 0.1?N HCl, phosphate buffer and hydroalcoholic solution. Burst drug release was exhibited by the uncoated tablets, probably due to high aqueous solubility of venlafaxine HCl. The coated tablets showed sustained drug release without burst effect. The drug release was best explained by Weibull model. A unified Weibull equation was evolved to express drug release from the coated tablets. The layered tablets also exhibited sustained release without burst effect due to effective area reduction. The optimized batches showed identical drug release in 0.1?N HCl, phosphate buffer and 10% v/v aqueous alcohol. Layered tablets may well be adopted by the industry due to the possibility of achieving a high production rate.     

盐酸川芎嗪口服定时释药微丸的制备

目的制备盐酸川芎嗪口服定时释药微丸。方法采用挤出滚圆法制备丸芯,底喷式流化床进行包衣,内层包衣选用水溶胀性高分子材料,外层包衣选用惰性高分子材料,考察了溶胀层、控释层及增塑剂的种类和用量等因素对药物释放的影响。结果随着溶胀层厚度的增加,释药时滞有一定程度的缩短;外层膜厚度增加或增塑剂用量增加,可显著延长时滞。结论制备盐酸川芎嗪口服定时释药微丸是可行的。     

一种产气型胃漂浮微丸的制备及其漂浮性和体外释放度的考察

目的以法莫替丁为模型药物,制备一种胃漂浮微丸,以延长胃内存留时间,提高药物的生物利用度。方法采用挤出滚圆法制备载药丸芯,以粉体学性质为指标进行处方筛选;采用流化床包衣的方法在载药丸芯外部包上产气层(含有碳酸氢钠的羟丙基甲基纤维素)和阻滞层(EudragitRL30D,RS30D,NE30D),并分别考察各处方微丸的漂浮性和体外释放性质。结果制得的微丸可以在5 min内起漂,持续漂浮达8 h以上,药物5 h缓释率达到93.5%。微丸的起漂时间随着产气物质[碳酸氢钠(NaHCO3)]质量的增加而缩短,随着外层阻滞层包衣增量的增加(EudragitNE30D)或Eudragit RS30D质量的增加(Eudragit RL30D/RS30D)而延长。结论试验制得的胃漂浮型微丸既能快速起漂、持续漂浮达8 h以上,又能缓慢释放药物。     

Evaluation of the compression characteristics and physical properties of the newly invented one-step dry-coated tablets

This study was conducted in order to clarify the compression characteristics, and to confirm the superiority of the physical properties, of the newly invented One-Step DRy-Coated tablets (OSDRC). We compared both the compression characteristics and the physical properties of OSDRC with those of physical-mixture tablets (PM) that were prepared with the same ingredients, quantity, and compression pressures. We selected potassium chloride (KCl) and acetaminophen (AAP) as the model drugs, since the former is known for its appropriate compression characteristics and the latter for its brittleness. The advantage of OSDRC is that they are capable of maintaining any kind of drug in their core, because the core is tightly surrounded by the outer layer, even when the drugs in the core have poor compression characteristics, which causes difficulties in forming a solid core tablet using conventional dry-coated tablet methods. The radial tensile strength of OSDRC was the same as, or superior to, that of PM containing of AAP. The results were in accordance with the compression process analysis performed according to Kawakita's equation. The friability of OSDRC was also superior to that of PM. These preferable characteristics were attributable to the high intensity of the OSDRC outer layer surface in comparison to that of PM. It was difficult to clarify the difference between OSDRC and PM in their physical properties when KCl was applied, since the tabletability of the whole tablet was high due to KCl's physical properties. The OSDRC containing AAP in their cores showed a controlled release pattern, though no other materials that have been known to influence drug release was present. It was considered that this controlled release pattern was caused by a reduced AAP particle surface area due to compression. It was confirmed with these experiments that the compression characteristics and the physical properties of AAP-OSDRC were superior to those of PM. These results indicated that it is possible to produce tablets that have materials with poor compression characteristics in the core portion, and high tabletability materials for the outer layers. In other words, it is possible to produce capsule-like tablets using the OSDRC compression method.     

Compressibility of Gastroretentive Pellets Coated with Eudragit NE Using a Single-Stroke and a Rotary Tablet Press

In this study, 15 kinds of powders with different compression mechanisms were used in the process of filling-binding substances in tablets with pellets. Applied substances possessed dominant brittle time-independent mechanism or time-dependent viscoplastic, viscoelastic mechanism of compression.

Using 6 kN compression force in a single-stroke tablet press during 150 ms of compression, damage to the polymer film and pellet core was found in all formulations. As a result, the authors observed an increase of releasing rate of verapamil hydrochloride (VH). A larger contact area between powders and pellets and connected with this better protective properties were ensured by powders with time-independent compression mechanism (eg, D-sorbitol or D-mannitol). Unsymmetrically applied compression force was a reason for inconsistent densification and insufficient protection of the pellets.

Taking into consideration the low rotation speed of the turret (10 rpm) in the rotary tablet press, the total compaction time was much longer than in the single-stroke tablet press. The compression time in the case of the rotary tablet press should be considered as the sum of the precompression (about 130 ms) and main compression (about 280 ms) phase times. Compression force applied by upper and lower punch in the precompression and main compression phase was affected uniformly on the pellets' surface, and when protected against fragmentation, allowed only some slight deformation. The powders in tablet formulation were fragmentized and rearranged independent of their compression mechanisms.

It was found that the releasing rate of VH from pellets compressed by rotary tablet press with 6, 12, and 18 kN of compression force was similar to the releasing rate from uncompressed pellets.     

Compressibility of gastroretentive pellets coated with Eudragit NE using a single-stroke and a rotary tablet press

In this study, 15 kinds of powders with different compression mechanisms were used in the process of filling-binding substances in tablets with pellets. Applied substances possessed dominant brittle time-independent mechanism or time-dependent viscoplastic, viscoelastic mechanism of compression. Using 6 kN compression force in a single-stroke tablet press during 150 ms of compression, damage to the polymer film and pellet core was found in all formulations. As a result, the authors observed an increase of releasing rate of verapamil hydrochloride (VH). A larger contact area between powders and pellets and connected with this better protective properties were ensured by powders with time-independent compression mechanism (eg, D-sorbitol or D-mannitol). Unsymmetrically applied compression force was a reason for inconsistent densification and insufficient protection of the pellets. Taking into consideration the low rotation speed of the turret (10 rpm) in the rotary tablet press, the total compaction time was much longer than in the single-stroke tablet press. The compression time in the case of the rotary tablet press should be considered as the sum of the precompression (about 130 ms) and main compression (about 280 ms) phase times. Compression force applied by upper and lower punch in the precompression and main compression phase was affected uniformly on the pellets' surface, and when protected against fragmentation, allowed only some slight deformation. The powders in tablet formulation were fragmentized and rearranged independent of their compression mechanisms. It was found that the releasing rate of VH from pellets compressed by rotary tablet press with 6, 12, and 18 kN of compression force was similar to the releasing rate from uncompressed pellets.     

Development of a method for nondestructive NIR transmittance spectroscopic analysis of acetaminophen and caffeine anhydrate in intact bilayer tablets

Calibration models for nondestructive NIR analysis of API (active pharmaceutical ingredient) contents in two separate layers of intact bilayer tablets were established. These models will enable the use of NIR transmittance spectroscopy in bilayer tableting processes for the control of API contents in separate layers. Acetaminophen and caffeine anhydrate were used as APIs, and tablets were made by the direct compression method. Their NIR spectra were measured in the transmittance mode. The reference assay was performed by HPLC. Calibration models were generated by the partial least-squares (PLS) regression. The initial calibration generated models with insufficient linearity and accuracy because the fluctuation range of tablet thickness was excessively large and irrelevant information on the thickness fluctuation was included in the models. By narrowing the fluctuation range to determine the proper range for acceptable prediction accuracy, it was confirmed that calibration models with less irrelevant information can be generated when the range was 4.30 ± 0.06 mm or narrower. Furthermore, the fluctuation range of 4.30 ± 0.06 mm was considered to be empirically valid in covering the fluctuation actually observed in ordinary tableting processes. Thus, the sample tablets within this range were used to generate the final calibration models, and calibration models sufficient in linearity and accuracy were established. In addition, it was proven that controlling the irradiated side was unnecessary. Namely, it is not necessary to keep the same side of sampled tablets for the online NIR analysis during bilayer tableting. It is useful, in order to obtain adequate calibration models, to evaluate the variable factors that affect the linearity and accuracy of the generated models and restrict the range of models or use a subset of prepared samples. Loading vectors, explained variances, and correlation coefficients between components and scores are important for the evaluation of variable factors.     

阿替洛尔单层芯渗透泵片的制备

目的以阿替洛尔为模型药物研究单层芯渗透泵片简化的制备方法，并进行处方优化。方法用自行设计的带针冲头压制带孔单层片芯， 以乙基纤维素为膜材包衣制备渗透泵片， 采用相似因子为指标筛选处方。结果 单层芯渗透泵片的片芯处方、包衣膜组成及厚度是影响释药的主要因素。在1.00～1.14 mm，片芯孔径对释药影响不大。结论本制备方法可免去激光打孔过程，制得的阿替洛尔单层芯渗透泵片能24 h匀速释药。     

Development of Dividable One-Step Dry-Coated Tablets (Dividable-OSDRC) and Their Evaluation as a New Platform for Controlled Drug Release

PURPOSE: The purpose of this study is to develop novel dividable coated tablets that retain their characteristics even after they are divided. METHODS: We prepared dividable one-step dry-coated tablets (dividable-OSDRC) using our own manufacturing process with double structure punches. The release pattern of the dividable-OSDRC with hydroxypropyl methylcellulose (HPMC) or methacrylic acid copolymer LD (Eudragit) as an outer layer was investigated before and after the division, and dissolution profiles were statistically compared using difference factor f1 and similarity factor f2. RESULTS: The dividable-OSDRC with HPMC for sustained-release (compression pressure, 150 MPa; crashing strength, 6.1 N; friability, 0.05%; CV of divided tablet weight, 7.8%) showed statistically equivalent release patterns between the one-half and the whole (f1, 13.9; f2, 55.5) and between the one-half and the two-halves (5.5, 72.5). The surface area of the tablets affected the sustained-release profiles. Furthermore, the tablets made with Eudragit LD for timed-release (150 MPa. 12.8 N, 0.18%, 9.6%) also showed approximated release patterns before and after the division. CONCLUSIONS: We proved that dividable-OSDRC maintain their release characteristics after they are divided. We conclude that the dividable-OSDRC could be used as a new platform for the controlled release of drugs.     

Preparation of the traditional Chinese medicine compound recipe Shuxiong sustained-release capsules by multiparticulate time-controlled explosion technology

In this study the traditional Chinese medicine compound recipe (TCMCR) Shuxiong sustained-release capsules (SXSRC) were prepared by multiparticulate time-controlled explosion technology. First, Shuxiong pellets were prepared with the refined medicinal materials containing in the recipe of Shuxiong tablets. Then, the pellets were coated sequentially with an inner swelling layer containing low-substituted hydroxypropylcellulose as the swelling agent and an outer rupturable layer of ethylcellulose. Finally, SXSRC were developed by encapsulating five kinds of pellets whose respective coating level of outer layer was 0%, 9%, 15%, 18% and 20% at equivalent ratio in hard gelatin capsules. Under the simulated gastrointestinal pH conditions, the in vitro release test of SXSRC was carried out. The value of similarity factor (f2) of hydroxysafflor yellow A and Panax notoginseng saponins, hydroxysafflor yellow A and ferulic acid, Panax notoginseng saponins and ferulic acid was 90.1, 77.3, 87.0, respectively. The release profiles of these three compositions from SXSRC showed a characteristic of obvious sustained-release and no significant difference between them. The results indicated that using multiparticulate time-controlled explosion technology various components in TCMCR with vastly different physicochemical properties could be released synchronously while sustained-releasing. That complies with the organic whole conception of compound compatibility of TCMCR.     

Characterization of 5-Fluorouracil Release from Hydroxypropylmethylcellulose Compression-Coated Tablets

Hydrogel compression-coated tablets are able to release the core drug after a period of lag time and have potential for colon-specific drug delivery based on gastrointestinal transit time concept. This study investigated the factors influencing in vitro release characteristics of a model drug 5-fluorouracil from hydroxypropylmethycellulose (HPMC) compression-coated tablets. The core tablet, prepared by a wet granulation compression method, was designed to disintegrate and dissolute quickly. To prepare the compression-coated tablets, 50% of the HPMC/lactose coat powder was precompressed first, followed by centering the core tablet and compressing with the other 50% of the coat powder. Release characteristics were evaluated in distilled water by using a Chinese Pharmacopoeia rotatable basket method. Effect of HPMC viscosity, lactose content in outer shell, and overall coating weight of outer shell on release lag time (T_lag), and zero-order release rate (k) were studied. Release of drug from compression-coated tablets began after a time delay as a result of hydrogel swelling/retarding effect, followed by zero-order release for most of the formulations studied. HPMC of higher viscosity (K4M and K15M) provided better protection of the drug-containing core, showing increased release lag time and slower release rate. Incorporating lactose in outer shell led to decrease of T_lag and increase of k. T_lag and k are exponentially and linearly correlated to lactose content, expressed as weight percentage of the outer shell. Larger coating weight (W) of outer shell produced larger coating thickness (D) around core tablet, which resulted in increase in T_lag and decrease in k. There was good fitting of a linear model for each of the four variables W, D, T_lag, and k. Hardness of the compression-coated tablets and pHs of the release media had little effect on drug release profile. It is concluded that the release lag time and release rate are able to be tailored through adjusting the formulation variables to achieve colon-specific drug delivery of 5-fluorouracil.     

The strength of bilayered tablets

The tensile strength of model materials (dicalcium phosphate dihydrate, microcrystalline cellulose and pregelatinised starch) compacted to form tablets in the form of beams consisting of two layers of equal thickness has been determined by three-point loading. The values of the tensile strength of the materials were sometimes higher and sometimes lower than the tensile strength of beams of the same thickness composed of a single material. Correction of the values for the tensile strength of the layered beams for the differences in the elasticity of the materials in the layered tablets failed to correct for these differences, as did considering the layered beams as beams of half thickness. For a layered tablet with pregelatinised starch at the bottom and microcrystalline cellulose at the top, the value of the tensile strength recorded appeared to be that of the microcrystalline cellulose as the fracture propagated across the boundary between the layers and into microcrystalline cellulose. What appeared to be the important factor was the way the failure of the beam crossed the interface between the two layers.