Rapidly Disintegrating Tablets Research Articles

Different types of pharmaceutical tablets used for treatment of diseases

In modern age of revolution and development in drug delivery for better clinical effects conventional dosages form have still a strong grip and most popular in all kinds of medicinal preparation intended for oral use. To satisfy the need of growing market tablets dosages form have incorporated modernization in producing and some advanced tablet types. Modified release tablet formulations including, layered tablets such as In +--lay tablet, Bi-layered tablet, Medicated chewing gum, Tablet tarts, Pastilles, Lollipop, Tablet inserts, Clinicaps, Caplets, Child ecstasy tablet and Tablet in tablet are new entries in pharmaceutical market. This review highlights the current advancements and patents in tablet technology. Recent advances in novel drug delivery system (NDDS) aims to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for ease of administration and to achieve better patient compliance. In the recent trend one such approach the development of rapid disintegrating tablets formulation is emerging and gaining popularity because it is easy to administer and leads to better patient compliance. These dosage forms are placed in the mouth, allowed to disperse or dissolve in the saliva. They release the drug as soon as they come in contact with the saliva, thus obviating the need for water during administration. The aim of this article is to review the progress of the evolving technologies and super disintegrating agents in the formulation, manufacturing and evaluation of these tablets. This article also discusses the new evaluation methodologies for these rapid disintegrating tablets. Various modifications in the conventional evaluation and use of specialized instruments are found to be essential in the testing of these dosage forms. In the present review the formulation techniques and different technologies are discussed.

Development and In-Vitro Evaluation of Plantago ovata Based Rapid Disintegrating Tablets of Labetalol Hydrochloride

Objectives: To avoid swallowing problems of conventional tablets and improved patient compliance Plantago Ovata based Labetalol HCl Rapid disintegrating tablets have been prepared. Methods: Six different (F1 to F6) batches of Labetalol HCl Rapid disintegrating tablets were developed by ‘direct compression method’ using Plantago ovata as a natural super-disintegrating agent. The formulated RDT were tested for angle of repose’, densities like tapped and bulk density, Hausner’s ratio, Carr’s index like pre-compression parameters and for thickness, weight variation or weight uniformity, tablet hardness, % drug content or content uniformity, water absorption ratio’, time require for wetting of tablets’ means wetting time, in-vitro drug disintegration time and in-vitro drug dissolution studies under post-compression parameters of evaluation. Results: It was found that the all the results of these pre-compression and post-compression parameters comply with official standards. The drug release was determined using dissolution media of pH 6.8 phosphate buffer through in-vitro dissolution of drug. This study showed that a rapid drug release by prepared tablets. The optimized formulation F6 showed higher water absorption ratio`, lower wetting time, minimum in-vitro disintegration time’ and higher drug release amongst all the formulations. The F6 formulation was considered the best among all formulations. Conclusion: The prepared rapid disintegrating tablets shows rapid onset of action by quick drug release, minimize side effects and enhanced patient compliance. These prepared tablets containing selective alpha-1 and non-selective beta adrenergic antagonist’ drug candidate Labetalol HCl, will be very useful in the treatment of high blood pressure with enhanced bioavailability.
 Keywords: Rapid disintegrating tablets, Labetalol Hydrochloride, Bioavailability Enhancement, Natural Superdisintegrant, Plantago Ovata, High Blood Pressure, RDT, Patient Compliance

Rapid disintegrating tablets: an effective method for accelerating the therapeutic action of poorly soluble Drugs

The ease of administration and increased patient compliance are critical factors in the design of oral drug delivery systems, which continue to be the dominant method of drug delivery despite numerous shortcomings. The rapid disintegrating tablet (RDT) could be a great alternative to traditional tablets because it dissolves quickly when it comes into contact with saliva. Rapid disintegrating tablets (RDTs) are currently more widely available than other tablets to treat various disorders. Due to its ease of manufacture and administration, oral administration is being investigated as the most frequently used route. Due to its rapid disintegration features, water-free use, and simplicity of swallowing, RDTs, particularly for pediatric patients, are effective drug delivery devices. Rapid disintegrating tablets are solid dosage forms that disintegrate in the mouth without water in less than 60 seconds. Rapid disintegration of tablets results in rapid dissolution and, thus, immediate action. The primary objective of this review paper is to discuss the benefits, drawbacks, formulation issues, manufacturing methods, patented technology and evaluation tests. Spray drying, freeze drying, direct compression, moulding, and sublimation are all traditional ways of preparation, however new technologies have been created for the production of RDTs.
 Keywords: Rapid disintegrating tablets, patient compliance, spray drying, freeze drying, direct compression.

New insights into the disintegration mechanism and disintegration profiling of rapidly disintegrating tablets (RDTs) by thermal imaging

In current studies, the disintegration process of tablets has been studied by thermal imaging. The study covers two major aspects; first, new revelations in the mechanism of tablet disintegration, and second, the development of disintegration test as a multi-point test by new thermometric and non-thermometric methods. The study has been carried out on fexofenadine rapidly disintegrating tablets (FEX RDTs) in a dark room cabinet fitted with a Fluke thermal imager and using water as the disintegration medium. The studies exhibit the existence of endothermic peaks during the early penetration of water in FEX RDTs. These endotherms are prominent at the starting point when the disintegration has just started, or the tablet has been just exposed to the water. Such endotherms have not been reported earlier for tablets and can be considered as a part of the wicking mechanism during disintegration. In later stages, when the water has completely wet the tablet, the endotherms are superimposed by exotherms. The endotherms or exotherms have also been used as a measurement of disintegration in the form of a new thermometric parameter, “area under temperature curve” (AUTC). Non-thermometric disintegration profiling by residual and subtraction methods is also performed. Among these, disintegration by the residual method, i.e., disintegration (residual) is newly introduced. In the end, the principal component analysis (PCA) describes the relationship between various disintegration methods, particle size distribution, and dissolution. PCA reveals that AUTC is the best method for studying the disintegration behavior of FEX RDTs.

Development and evaluation of solid dispersion based rapid disintegrating tablets of poorly water-soluble anti-diabetic drug

Glimepiride is an effective oral hypoglycemic agent that lowers the glucose level of blood by stimulating insulin release from beta cells of the pancreas. However, the poor aqueous solubility (i.e., <0.004 mg/ml) and wettability of drug pose hurdles in the formulation of drug delivery vehicles. In this research work, we have attempted to develop rapid disintegrating tablets (RDT) of glimepiride solid dispersion. Gelucire 50/13, PEG 4000 and PEG 6000 were employed as polymeric carriers to formulate solid dispersions by kneading and spray drying techniques and were characterized by FTIR, DSC, saturation solubility analysis, drug content, and in vitro dissolution studies.From the obtained data, it was exhibited that the improvement in solubility and dissolution was highest for 1:3 spray-dried solid dispersion of glimepiride with gelucire 50/13 (batch A6). The RDT was prepared using the optimized batch of solid dispersion and was tested for hardness, thickness, drug content, weight variation, friability, disintegration time, and in vitro dissolution studies. The optimized batch (F7-A6) showed maximum cumulative drug release within the minimum period. It also exhibited a higher dissolution profile in comparison to the marketed tablet. From the stability studies carried out on RDT formulation, it was revealed that the tested tablets were quite stable. Hence, the rapid disintegrating tablet of the poorly water-soluble drug, glimepiride, could be a promising strategy for the development of better anti-diabetic drug delivery carriers.

In-vivo disintegration and absorption of two fast acting aspirin tablet formulations compared to ibuprofen tablets using pharmacoscintigraphy

IntroductionAspirin is widely used to relieve acute pain and reduce fever and inflammation. New 500 mg and 1000 mg aspirin rapid disintegrating tablets with small active ingredient particle size and sodium carbonate excipient were developed to replace regular 500 mg aspirin tablet formulation containing starch and cellulose. The rapid disintegrating aspirin tablets have been proven to show faster in-vitro dissolution and a shorter time to Cmax (Voelker 2012) resulting in faster pain relief (Cooper 2012). The current study correlates the site and time to complete tablet disintegration with the plasma concentration time profile, using γ-scintigraphy imaging technique. Two 400 mg ibuprofen tablet formulations (ibuprofen acid and ibuprofen lysine salt) have also been analyzed in this study. MethodsOpen label, randomized and four-way crossover trial in 12 healthy fasted males. Scintigraphy images and blood sampling were taken up to 4 h post dose. Tablets were radiolabelled with 4 MBq technetium (99mTc)-labelled DTPA using a drill and fill method (Wilson 2003). Site and time to complete tablet disintegration were derived from the scintigraphy images. Validated bioassays were used to measure plasma concentration. ResultsIn all subjects the aspirin formulations disintegrated rapidly and completely in the stomach (500 mg Aspirin: 9.0 min, 1000 mg Aspirin: 5.0 min). Complete disintegration of the ibuprofen tablets occurred in 5 and 4 out of 12 subjects in the small intestine. Time to complete disintegration was longer (acid: 37.5 min, lysine-salt: 37.5 min) than with the aspirin formulations. This correlates with pharmacokinetics: a substantial difference in Tmax between the two aspirin formulations (500 mg Aspirin: 20 min, 1000 mg Aspirin: 23 min) and the two ibuprofen formulations (acid: 68 min, lysine-salt: 42 min) was observed. ConclusionsThe gastrointestinal disintegration and systemic absorption of the aspirin formulations is faster compared to the ibuprofen formulations.

Formulation and characterization of oral rapid disintegrating tablets of levocetirizine.

Levocetirizine, active R (-) enantiomer of cetirizine, is an orally active and selective H1 receptor antagonist used medically as an anti-allergic. Allergic rhinitis is a symptomatic disorder of the nose induced by inflammation mediated by immunoglobulin E (IgE) in the membrane lining the nose after allergen exposure. The purpose of the present study was to prepare rapidly disintegrating tablets of levocetirizine after its complexation with β-cyclodextrin (β-CD). Levocetirizine-β-CD complex tablets were prepared by direct compression technique using 3 synthetic superdisintegrants in different proportions. Development of the formulation in the present study was mainly based on the concentration of superdisintegrants and the properties of the drug. Nine batches of tablets were formulated and evaluated for various parameters: drug content, weight variation, water absorption ratio, wetting time, in vitro disintegration, hardness, friability, thickness uniformity, and in vitro dissolution. A Fourier-transform infrared spectroscopy (FTIR) study showed that there were no significant interactions between the drug and the excipients. The prepared tablets were good in appearance and showed acceptable results for hardness and friability. The in vitro disintegrating time of the formulated tablet batches was found to be 15-35 s percentage and the drug content of tablets in all formulations was found to be between 90-102%, which complied with the limits established in the United States Pharmacopeia. Complexation of levocetirizine with β-CD significantly improves the solubility of the drug. The disintegration time of the tablets was decreased with an increase in superdisintegrant amount. The tablets (batch CPX5) had a minimum disintegration time of 20 s and 99.99% of the drug was released within 10 min.

Management of breast cancer in the elderly. Is treatment changing over time?

Aspirin is widely used to relieve acute pain and reduce fever and inflammation. New 500 mg and 1000 mg aspirin rapid disintegrating tablets with small active ingredient particle size and sodium carbonate excipient were developed to replace regular 500 mg aspirin tablet formulation containing starch and cellulose. The rapid disintegrating aspirin tablets have been proven to show faster in-vitro dissolution and a shorter time to Cmax (Voelker 2012) resulting in faster pain relief (Cooper 2012). The current study correlates the site and time to complete tablet disintegration with the plasma concentration time profile, using γ-scintigraphy imaging technique. Two 400 mg ibuprofen tablet formulations (ibuprofen acid and ibuprofen lysine salt) have also been analyzed in this study.Open label, randomized and four-way crossover trial in 12 healthy fasted males. Scintigraphy images and blood sampling were taken up to 4 h post dose. Tablets were radiolabelled with 4 MBq technetium (99mTc)-labelled DTPA using a drill and fill method (Wilson 2003). Site and time to complete tablet disintegration were derived from the scintigraphy images. Validated bioassays were used to measure plasma concentration.In all subjects the aspirin formulations disintegrated rapidly and completely in the stomach (500 mg Aspirin: 9.0 min, 1000 mg Aspirin: 5.0 min). Complete disintegration of the ibuprofen tablets occurred in 5 and 4 out of 12 subjects in the small intestine. Time to complete disintegration was longer (acid: 37.5 min, lysine-salt: 37.5 min) than with the aspirin formulations. This correlates with pharmacokinetics: a substantial difference in Tmax between the two aspirin formulations (500 mg Aspirin: 20 min, 1000 mg Aspirin: 23 min) and the two ibuprofen formulations (acid: 68 min, lysine-salt: 42 min) was observed.The gastrointestinal disintegration and systemic absorption of the aspirin formulations is faster compared to the ibuprofen formulations.

Effect of xanthan gum as a thickener in widely-used food thickeners on the disintegration of rapidly-disintegrating tablets

Effect of xanthan gum as a thickener in widely-used food thickeners on the disintegration of rapidly-disintegrating tablets

Development of a solid dosage platform for the oral delivery of bilayer vesicles

Within this work, we develop vesicles incorporating sub-unit antigens as solid dosage forms suitable for the oral delivery of vaccines. Using a combination of trehalose, dextran and mannitol, freeze-dried oral disintegrating tablets were formed which upon rehydration release bilayer vesicles incorporating antigen. Initial studies focused on the optimisation of the freeze-dry cycle and subsequently excipient content was optimised by testing tablet hardness, disintegration time and moisture content. The use of 10% mannitol and 10% dextran produced durable tablets which offered strong resistance to mechanical damage yet appropriate disintegration times and dispersed to release niosomes-entrapping antigen. From these studies, we have formulated a bilayer vesicle vaccine delivery system as rapid disintegrating tablets and capsules.

Rapid disintegrating tablets of simvastatin dispersions in polyoxyethylene-polypropylene block copolymer for maximized disintegration and dissolution.

The objective of this research was to improve the dissolution of simvastatin and to incorporate it in rapid disintegrating tablets (RDTs) with an optimized disintegration and dissolution characteristics. Polyoxyethylene–polypropylene block copolymer (poloxamer 188) was employed as a hydrophilic carrier to prepare simvastatin solid dispersions (SDs). Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffractometry were employed to understand the interaction between the drug and the carrier in the solid state. The results obtained from Fourier transform infrared spectroscopy showed absence of any chemical interaction between the drug and poloxamer. The results of differential scanning calorimetry and X-ray diffractometry confirmed the conversion of simvastatin to distorted crystalline state. The SD of 1:2 w/w drug to carrier ratio showed the highest dissolution; hence, it was incorporated in RDT formulations using a 32 full factorial design and response surface methodology. The initial assessments of RDTs demonstrated an acceptable flow, hardness, and friability to indicate good mechanical strength. The interaction and Pareto charts indicated that percentage of croscarmellose sodium incorporated was the most important factor affecting the disintegration time and dissolution parameter followed by the hardness value and their interaction effect. Compression force showed a superior influence to increase RDT’s porosity and to fasten disintegration rather than swelling action by croscarmellose sodium. On the other hand, croscarmellose sodium was most important for the initial simvastatin release. The results suggest the potential use of poloxamer 188-based SD in RDT for the oral delivery of poor water-soluble antihyperlipidemic drug, simvastatin.

Using Texture Analysis Technique to Assess the Freeze-Dried Cakes in Vials

A freeze-dried (FD) cake should possess, among other properties, a sufficient dryness and strength to prevent cracking or powdering during transportation and storage. In this study, the application of a standard texture analysis (TA) technique to study the mechanical properties of the FD cakes directly in glass vials used for freeze-drying has been demonstrated. Examining the FD cakes in glass vials has many advantages as it allows studying the intact FD cakes minimizing the bias from texture distortion during samples preparation, and reducing the moisture uptake. A procedure allowing quantitative assessment of the strength, fracturability, and elastic properties of the FD cakes using TA has been developed. The results show that the TA method is sensitive to the variations in cake materials, storage conditions (temperature, excessive moisture), and cake quality. The results also show that TA can also be applied for optimization and improvement of the freeze-drying protocols and rapid disintegrating tablet formulation development. The simplicity of the TA technique and a number of different probes available on the market allow using the TA for the routine reliable and robust tests of FD solids providing valuable information on the strength and texture of the cakes.

Studies and evaluation of compressed microspheres

AbstractThis work was aimed at the use of dissolution testing and similarity factor to assess the level of damage taken by active drug microspheres during compression in tablet dosage form. To achieve that, combinations of suitable excipients were used to protect drug microspheres during compression. The excipients were used in the form of powders, granules or placebo pellets prepared by extrusion-spheronization technology. The excipients were evaluated alone, in combinations and post-compression into compacts. Preliminary experiments included assessing density, hardness, friability and disintegration of all the selected excipients. Based on such experiments it was found that the flowability of combination of powders was more acceptable than individual excipients. Two combinations of microcrystalline -starch and microcrystalline cellulose -calcium carbonate granules were selected to be compressed with pellets of the active pharmaceutical ingredient ketoprofen. In all the combinations used there was a significant amount of damage to drug pellets. The kinetics of drug release appears to follow the zero-order rate, which remained unchanged even when a significant degree of damage to pellets occurs. It was found that a high level of excipients is required in order to prepare microspheres as a rapid disintegrating tablet.

A review on fast dissolving tablet

These tablets are distinguished from conventional sublingual tablets, lozenges, and buccal tablets which require more than a minute to dissolve in the mouth. In the literature, ODTs also are called orally disintegrating, orodisperse, mouth-dissolving, quick-dissolve, fast-melt, and rapid-disintegrating tablets. Over the past three decades, orally disintegrating tablets (ODTs) have gained much attention as a preferred alternative to conventional oral dosage forms such as tablets and capsules. An ODT is a solid dosage form that disintegrates and dissolves in the mouth (either on or beneath the tongue or in the buccal cavity) without water within 60 seconds or less. The desire of improved palatability in orally administered products has prompted the development of numerous formulations with improved performance and acceptability, and the field has become a rapidly growing area in the pharmaceutical industry. The unique property of mouth dissolving tablet is that they are rapidly disintegrating and/or dissolving and release the drug as soon as they come in contact with saliva, thus obviate the requirement of water during administration. This article reviews the earlier applications and methodologies of taste masking and also emphasize on the recent developments and approaches of bitterness reduction for orally used pharmaceuticals. Apart from the conventional methods of fabrication, this review also provides the detailed concept of some unique patents; technologies developed and marketed formulations of Mouth Dissolving Tablets (MDTs).

FORMULATION AND EVALUATION OF CHLORPHENOXAMINE HYDROCHLORIDE RAPIDLY DISINTEGRATING TABLETS

Th e aim of the present study was to develop rapid disintegrating tablets of C hlorophenoxamine hydrochloride which acts as antihistaminic , anticholinergic , antipruritic and antiparkinsonian agent . Chlorphenoxamine Hydrochloride is present in the market as conventional tablets with very low bioavailability due to first pass effect . To increase its bioavailability; rapidly disintegrating tablets of chlorophenoxamine hydrochloride to be dissolved and disintegrate quickly in the mouth cavity and reach to the systemic circulation more quickly than conventional tablets. Rapid disintegrating tablets o f Chlorophenoxamine h ydrochloride were prepared by using different superdisintegrants such as Aci - Di - Sol, crosspovidone and sodium starch glycolate with two different concentrations 2.5 mg and 5 mg . The blend was examined for angle of repose, bulk density, tapped density, compressibility index and Hausner’s ratio. The compressed tablets were evaluated for drug content, friability, disintegration time in - vitro , wetting time and dissolution rate. The flowability tests and the q uality control tests for tablets were done and good results were obtained for all formulae. In vitro dissolution studies showed the releas e in the following descending order of superdisintegrants: Crospovidone > Croscarmellose s odium > Sodium Starch Glycolate . S election of the best formula was done and it was found that F6 the formula which contains Crosspovidone 5 mg showed the fastest disi ntegration time in 16 seconds and drug release about 100 % in 8 minutes. The accelerated stability study was done for formula F6 . It was concluded that Crosspovidone at a concentration of 5 mg is suitable for preparing rapid disintegrating tablet s of Chlor ophenoxamine hydrochloride.

Functionality of disintegrants and their mixtures in enabling fast disintegration of tablets by a quality by design approach.

Investigation of the effect of disintegrants on the disintegration time and hardness of rapidly disintegrating tablets (RDTs) was carried out using a quality by design (QbD) paradigm. Ascorbic acid, aspirin, and ibuprofen, which have different water solubilities, were chosen as the drug models. Disintegration time and hardness of RDTs were determined and modeled by executing combined optimal design. The generated models were validated and used for further analysis. Sodium starch glycolate, croscarmellose sodium, and crospovidone were found to lengthen disintegration time when utilized at high concentrations. Sodium starch glycolate and crospovidone worked synergistically in aspirin RDTs to decrease disintegration time. Sodium starch glycolate-crospovidone mixtures, as well as croscarmellose sodium-crospovidone mixtures, also decreased disintegration time in ibuprofen RDTs at high compression pressures as compared to the disintegrants used alone. The use of sodium starch glycolate in RDTs with highly water soluble active ingredients like ascorbic acid slowed disintegration, while microcrystalline cellulose and crospovidone drew water into the tablet rapidly and quickened disintegration. Graphical optimization analysis demonstrated that the RDTs with desired disintegration times and hardness can be formulated with a larger area of design space by combining disintegrants at difference compression pressures. QbD was an efficient and effective paradigm in understanding formulation and process parameters and building quality in to RDT formulated systems.

Pharmacokinetic and Safety Analyses of Tenofovir and Tenofovir-Emtricitabine Vaginal Tablets in Pigtailed Macaques

Vaginal rapidly disintegrating tablets (RDTs) containing tenofovir (TFV) or TFV and emtricitabine (FTC) were evaluated for safety and pharmacokinetics in pigtailed macaques. Two separate animal groups (n = 4) received TFV (10 mg) or TFV-FTC (10 mg each) RDTs, administered near the cervix. A third group (n = 4) received 1 ml TFV gel. Blood plasma, vaginal tissue biopsy specimens, and vaginal fluids were collected before and after product application at 0, 0.5, 1, 4, and 24 h. A disintegration time of <30 min following vaginal application of the RDTs was noted, with negligible effects on local inflammatory cytokines, vaginal pH, and microflora. TFV pharmacokinetics were generally similar for both RDTs and gel, with peak median concentrations in vaginal tissues and vaginal secretions being on the order of 10(4) to 10(5) ng/g (147 to 571 μM) and 10(6) ng/g (12 to 34 mM), respectively, at 1 to 4 h postdose. At 24 h, however, TFV vaginal tissue levels were more sustained after RDT dosing, with median TFV concentrations being approximately 1 log higher than those with gel dosing. FTC pharmacokinetics after combination RDT dosing were similar to those of TFV, with peak median vaginal tissue and fluid levels being on the order of 10(4) ng/g (374 μM) and 10(6) ng/g (32 mM), respectively, at 1 h postdose with levels in fluid remaining high at 24 h. RDTs are a promising alternative vaginal dosage form, delivering TFV and/or FTC at levels that would be considered inhibitory to simian-human immunodeficiency virus in the macaque vaginal microenvironment over a 24-h period.

A THz spectroscopy method for quantifying the degree of crystallinity in freeze-dried gelatin/amino acid mixtures: An application for the development of rapidly disintegrating tablets

In rapidly disintegrating tablets (RDTs) manufactured by freeze-drying processes, the % crystallinity of the freeze-dried matrix underpins the physical properties such as mechanical strength and dissolution profile. This study examines the feasibility of using terahertz pulsed spectroscopy (TPS) as an off-line tool (in the first instance) for assessing the degree of crystallinity in co-freeze dried amino-acid/gelatine mixtures. Three amino acids (l-alanine, serine and proline) were studied by TPS (in the wave number range of 3-100cm(-1)) both in the pure crystalline form and in the form of a co-freeze-dried matrix with gelatin (in weight fractions of 10:90, 30:70, 50:50, and 70:30). In co-freeze dried proline/gelatin matrix no crystallinity was observed using TPS, whereas ~62±1% (n=3) and 72±0.5% (n=3) crystallinity was observed in the co-freeze dried alanine/gelatin matrix (50% w/w and 70% w/w, respectively). Similarly, ~41±0.5% (n=3) and ~80±0.5% (n=3) crystallinity was observed in the serine/gelatin matrix (30% w/w and 50% w/w respectively). The potential for using TPS as a quantitative in-line tool for determining the degree of crystallinity in a range of complex systems such as RDTs, conventional tablets, sprayed dried micro particles, is suggested from these results.

Development of a Novel and Simple Method to Evaluate Disintegration of Rapidly Disintegrating Tablets

The purpose of this study was to develop and test a novel and simple method for evaluating the disintegration time of rapidly disintegrating tablets (RDTs) in vitro, since the conventional disintegration test described in the pharmacopoeia produces poor results due to the difference of its environmental conditions from those of an actual oral cavity. Six RDTs prepared in our laboratory and 5 types of commercial RDTs were used as model formulations. Using our original apparatus, a good correlation was observed between in vivo and in vitro disintegration times by adjusting the height from which the solution was dropped to 8 cm and the weight of the load to 10 or 20 g. Properties of RDTs, such as the pattern of their disintegrating process, can be assessed by verifying the load. These findings confirmed that our proposed method for an in vitro disintegration test apparatus is an excellent one for estimating disintegration time and the disintegration profile of RDTs.

Preparation and evaluation of pectin-based colon-specific pulsatile capsule in vitro and in vivo

The purpose of this study was to develop and evaluate a colon-specific, pulsatile drug delivery system, which consists of an impermeable capsule body filled with a 5-aminosalicylic acid rapid-disintegrating tablet and a pectin-based erodible plug placed in the opening of the capsule body. To obtain an appropriate gel-forming ability and suitable lag time for the colon-specific drug delivery, high-methoxy pectin (HM-pectin) was formulated with lactose and lowmethoxy pectin (LM-pectin) with HPMC to prepare the plug tablet. In order to evaluate the lag time, prior to the rapid drug release, both the formulation of the plug tablet and in vitro release medium were studied. The lag time prior to the rapid drug release was mainly determined by the HM-pectin/lactose or LM-pectin/HPMC ratio. The addition of pectinase or rat cecal content into the release medium shortened the lag time significantly, which predicted the probable enzyme sensitivity of pectin plug tablet. In vivo studies showed that the plasma concentration of drug can only be detected 6h after oral administration of the pulsatile capsule, which indirectly proved the colon-specific characteristics. These results show that the pulsatile capsule may have the therapeutic action for colon-specific drug delivery.