The influence of swelling capacity of superdisintegrants in different pH media on the dissolution of hydrochlorothiazide from directly compressed tablets

The purpose of this study was to investigate the efficiency of superdisintegrants in promoting tablet disintegration and drug dissolution under varied media pH. Significant reductions in the rate and extent of water uptake and swelling were observed for both sodium starch glycolate (Primojel) and croscarmellose sodium (Ac-Di-Sol) in an acidic medium (0.1 N HCl) but not for crospovidone NF (Polyplasdone XL10), a nonionic polymer. When Primojel and Ac-Di-Sol were incorporated in model formulations, a significant increase in tablet disintegration time was observed for slowly disintegrating tablets (lactose-based tablets) but not for the rapidly disintegrating tablets (dicalcium phosphate-based tablets). The dissolution rate of the model drug, hydrochlorothiazide, was found highly dependent on both tablet disintegration efficiency and the solubility of base material(s) in the testing medium. A laser diffraction particle size analyzer proved to be an effective tool for determining the intrinsic swelling of disintegrant particles in different media. Water uptake and swelling were confirmed as 2 important functions of superdisintegrants. The reduced water uptake and swelling capacity of disintegrants containing ionizable substituents in an acidic medium can potentially jeopardize their efficiency in promoting tablet disintegration and the drug dissolution rate. Published: September 20, 2005     

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.KEY WORDS: disintegrants, quality by design, rapidly disintegrating tablets     

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach

The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60–70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus- and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (<15 min) and acceptable TS (≥1 MPa at 10–15% tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies.     

Development and Characterization of Enteric-Coated Immediate-Release Pellets of Aceclofenac by Extrusion/Spheronization Technique Using κ-Carrageenan as a Pelletizing Agent

In the present study, an attempt was made to prepare immediate-release enteric-coated pellets of aceclofenac, a poorly soluble nonsteroidal anti-inflammatory drug that has a gastrointestinal intolerance as its serious side effect. Formulation of enteric-coated pellets with improved solubility of aceclofenac could address both of these problems. To achieve these goals, pellets were prepared by extrusion–spheronization method using pelletizing agents that can contribute to the faster disintegration and thereby improve the solubility of the drug. Different disintegrants like β-cyclodextrin, kollidon CL, Ac-Di-Sol, and sodium starch glycolate were tried in order to further improve disintegration time. The pellets were characterized for drug content, particle size distribution, flow properties, infrared spectroscopy, surface morphology, disintegration rate, and dissolution profile. The formulations, which showed best disintegration and dissolution profiles, were coated with Eudragit L100-55, an enteric-coated polymer which does not dissolve at gastric pH but dissolves at intestinal pH, releasing the drug immediately in the dissolution medium. The optimized enteric-coated formulation containing 20% κ-carrageenan, lactose, and sodium starch glycolate as a disintegrant did inhibit the release of the drug for 2 h in 0.1 N HCl, whereas 87% of the drug was released within 45 min. The improvement was substantial when it was compared with solubility of pure drug under the same conditions. Thus, dissolution profiles suggested that combination of κ-carrageenan and sodium starch glycolate resulted into fast-disintegrating, immediate-release pellets, overcoming the bioavailability problem of the poorly soluble drug, aceclofenac, and enteric coating of these pellets avoids the exposure of aceclofenac to ulcer-prone areas of the gastrointestinal tract.     

Impact of Physicochemical Environment on the Super Disintegrant Functionality of Cross-Linked Carboxymethyl Sodium Starch: Insight on Formulation Precautions

The aim of this work is to improve the understanding of the physicochemical mechanisms involved in the functionality of cross-linked carboxymethyl sodium starch (CCSS) as a tablet super disintegrant (SD). The behavior and properties of this SD (medium uptake, disintegration times, particle size, and rheology) was investigated in a wetting medium of different physicochemical properties. In particular, the relative permittivity (dielectric constant) of these media was intentionally modified for evaluating its effect on CCSS properties. Results showed different swelling behaviors of CCSS particles according to the relative permittivity of the tested media and allow to propose two underlying mechanisms that explain CCSS functionality. Both the intra-particular swelling and the inter-particular repulsion are affected by the relative permittivity of the media. Finally, disintegration test performed on tablets specially formulated with mannitol (used commonly as an excipient and known to modify relative permittivity) confirmed that the functionality of CCSS and therefore the disintegration of the tablet can be altered according to the mannitol content.KEY WORDS: cross-linked carboxymethyl sodium starch, disintegrant functionality, orally disintegrating tablets, relative permittivity, repulsive layers     

Effect of Sorbed Water on Disintegrant Performance of Four Brands of Polacrilin Potassium NF

Polacrilin Potassium NF is a commonly used weak cation exchange resin disintegrant in pharmaceutical tablets. The objective of this research was to evaluate the effects of sorbed moisture on physical characteristics and disintegrant performance of four brands of Polacrilin Potassium NF. The disintegrants were stored in five different relative humidity chambers and their dynamic vapor adsorption–desorption analysis, effect of moisture on their compressibility, compactability, particle size, morphology, water uptake rate, and disintegration ability were studied. Moisture seemed to plasticize the disintegrants, reducing their yield pressures. However, certain optimum amount of moisture was found to be useful in increasing the compactablity of the tablets containing disintegrants. The tablets, however, lost their tensile strengths beyond this optimum moisture content. Moisture caused two brands of the disintegrants to swell; however, two other brands aggregated upon exposure to moisture. Swelling without aggregation increased the water uptake, and in turn the disintegrant performance. However, aggregation probably reduced the porosities of the disintegrants, reducing their water uptake rate and disintegrant performance. Different brands of Polacrilin Potassium NF differed in the abilities to withstand the effects of moisture on their functionality. Effect of moisture on disintegrant performance of Polacrilin Potassium NF needs to be considered before its use in tablets made by wet granulation.     

Formulation and Optimization of Orodispersible Tablets of Diazepam

Diazepam is one of the most prescribed benzodiazepines. The purpose of the present research was to optimize the formulation of orodispersible tablets of diazepam. Orodispersible tablets of diazepam were prepared using different types of superdisintegrants (Ac-Di-Sol, sodium starch glycolate, and crospovidone (CP)) and different types of subliming agents (camphor and ammonium bicarbonate (AB)) at different concentrations and two methods of tablets preparations (wet granulation and direct compression methods). The formulations were evaluated for flow properties, wetting time, hardness, friability, content uniformity, in vivo disintegration time (DT), release profiles, and buccal absorption tests. All formulations showed satisfactory mechanical strength except formula F5 which contains camphor and formula F9 which is prepared by direct compression method. The results revealed that the tablets containing CP as a superdisintegrant have good dissolution profile with shortest DT. The optimized formula F7 is prepared using 10% CP as a superdisintegrant and 20% AB as a subliming agent by wet granulation method which shows the shortest DT and good dissolution profile with acceptable stability. This study helps in revealing the effect of formulation processing variables on tablet properties. It can be concluded that the orodispersible tablets of diazepam with better biopharmaceutical properties than conventional tablets could be obtained using formula F7.     

Comparative effects of different cellulosic-based directly compressed orodispersable tablets on oral bioavailability of famotidine

Famotidine is a potent H₂-receptor antagonist most commonly used by elderly patients. Orodispersible tablets (ODT) are gaining popularity over conventional tablets due to their convenience and suitability for patients having dysphagia. The purpose of this study is to prepare famotidine ODT using the economic direct-compression method.A 3² full factorial design was used to evaluate the influence of different excipients on the properties and in vitro dissolution of famotidine ODT. Two factors were studied for their qualitative effects, namely, disintegrants and diluents. Disintegrants were studied in three levels viz. Ac-Di-Sol, sodium starch glycolate (Primojel) and low-substituted hydroxypropyl cellulose (L-HPC). Fillers were studied in three levels viz. mannitol, spray dried lactose and Avicel PH 101. The ODTs were prepared by direct compression and were evaluated for hardness, drug content, uniformity of weight, in vitro disintegration time, oral disintegration time, wetting time and in vitro dissolution. Maximum dissolution and minimum oral disintegration time (11.4 s) were observed in F7 prepared using L-HPC and mannitol. Furthermore, in human volunteers it showed significant increase in bioavailability compared to Servipep^® with mean AUC_(0–∞) 117.1 ng/ml and 82.71 ng/ml, respectively, and its relative bioavailability was 141.57%. Hence, ODT (F7) could possibly be used to overcome the drawbacks of conventional famotidine tablets in elderly patients with significant increase in oral bioavailability.     

Formulation and Evaluation of Swellable and Floating Gastroretentive Ciprofloxacin Hydrochloride Tablets

Drugs that have narrow absorption window in the gastrointestinal tract (GIT) will have poor absorption. For these drugs, gastroretentive drug delivery systems offer the advantage in prolonging the gastric emptying time. Swellable, floating, and sustained release tablets are developed by using a combination of hydrophilic polymer (hydroxypropyl methylcellulose), swelling agents (crospovidone, sodium starch glycolate, and croscarmelose sodium) and effervescent substance (sodium bicarbonate). Formulations are evaluated for percentage swelling, in vitro drug release, floating lag time, total duration of floating, and mean residence time (MRT) in the stomach. The drug release of optimized formulation follows the Higuchi kinetic model, and the mechanism is found to be non-Fickian/anomalous according to Krosmeyer–Peppas (n value is 0.68). The similarity factor (f ₂) is found to be 26.17 for the optimized formulation, which the release is not similar to that of marketed produced (CIFRAN OD®). In vivo nature of the tablet at different time intervals is observed in the radiographic pictures of the healthy volunteers and MRT in the stomach is found to be 320?±?48.99 min (n?=?6). A combination of HPMC K100M, crospovidone, and sodium carbonate shows the good swelling, drug release, and floating characters than the CIFRAN OD®.     

Formulation and in-vitro characterization of fast-disintegrating herbal extract sublingual immunotherapy tablet for peanut-induced allergic asthma

BackgroundAllergen immunotherapy (AIT) involves the regimen of gradually incrementing doses of the allergen, thereby inducing desensitization and tolerance. Sublingual Immunotherapy tablets (SLIT-tablets) have been formulated for several allergies and had manifested efficacy for allergic rhinitis and allergic asthma. SLIT promises an alternative method to other routes of AIT enabling patients to self-administer AIT.ObjectiveThe study aimed to formulate fast disintegrating SLIT containing crude peanut extract for peanut-induced allergic asthma.MethodsThe crude peanut extract was prepared by a simple extraction method and was subjected to quantitative and qualitative analysis. The extract was also characterised for its physical properties. The preformulation study for the extract and excipients of the tablet was performed using FT-IR spectroscopy and Differential scanning calorimetry. The tablet powder blends were characterised for pre-compression properties. The SLIT tablets were developed by direct compression and the post-compression evaluation was performed.ResultsThe results of the quantitative and qualitative analysis of extract confirmed the presence of peanut proteins in the extract. The preformulation studies using FT-IR spectroscopy and Differential Scanning Calorimetry revealed that there is no significant interaction between the CPE and excipients. The pre-compression characterisation showed that the powder blends had good flowproperties. Three doses of SLIT tablets were formulated with each dose containing four batches and the tablet of each dose was optimized by studying the effect of varying concentrations of super disintegrants on disintegration time and dissolution rate. The post compression characterization of the tablets was performed and the optimized batch of the three doses with the concentration of 5% crospovidone and 2% croscarmellose sodium showed less wetting time and high-water absorption ratio, shorter disintegration time of 14secs and maximum drug release of >90% within 2–3 min.ConclusionThe results indicated the suitability of formulated SLIT tablets for peanut induced allergic asthma.     

Preparation of Spherical Crystal Agglomerates of Naproxen Containing Disintegrant for Direct Tablet Making by Spherical Crystallization Technique

The purpose of this research was to obtain directly compressible agglomerates of naproxen containing disintegrant by spherical crystallization technique. Acetone–water containing hydroxypropyl celloluse (HPC) and disintegrant was used as the crystallization system. In this study croscarmellose sodium (Ac–Di–Sol) was employed as disintegrant. The agglomerates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD), and scanning electron microscopy and were evaluated for flow, packing and tableting properties and drug release. The growth of particle size and the spherical form of the agglomerates resulted in formation of products with good flow and packing properties. The improved compaction properties of the agglomerated crystals were due to their fragmentation occurred during compression. DSC and XRPD studies showed that naproxen particles, crystallized in the presence of HPC and Ac–Di–Sol did not undergo structural modifications. The dissolution rate of naproxen from tablets made of naproxen–(Ac–Di–Sol) agglomerates was enhanced significantly because of including the disintegrant in to the particles. This was attributed to an increase in the surface area of the practically water insoluble drug is exposed to the dissolution medium. In conclusion the spherical crystallization technique developed in this study is suitable for obtaining agglomerates of drug with disintegrant.     

Effect of Different Excipients on the Physical Characteristics of Granules and Tablets with Carbamazepine Prepared with Polyethylene Glycol 6000 by Fluidized Hot-Melt Granulation (FHMG)

The objective of this study was to investigate the properties of granules and tablets with carbamazepine which were prepared employing a fluidized hot-melt granulation (FHMG) technique. The FHMG process was carried out at 65°C. Macrogol 6000 (PEG 6000) was used as a binder at the content 10% (w/w) of the granulated mass. Granules containing up to 70% (w/w) of the drug and 20–90% (w/w) of a filler (lactose, mannitol, calcium hydrogen phosphate (Di-Cafos), pregelatinized starch, and microcrystalline cellulose (MCC)) were produced. When the drug content was 30% (w/w), the yield of the process was satisfying (>95%) and flowability of the granules was better than placebo granules or drug-loaded granules prepared by wet granulation. Type of a filler had strong impact on physical properties of granules, and size distribution of the particles was the most homogenous when lactose or Di-Cafos were used. The FHMG technique enabled preparation of granules with better compressability compared with the wet-granulated product or with non-granulated powders. Tablets with shorter disintegration time than 10 min were obtained with 2.0% crospovidone added as a disintegrant. In comparison to tablets prepared from the wet-granulated mass, employment of the FHMG method resulted in tablets with faster dissolution of carbamazepine (more than 80% of the drug released within 15 min). This was achieved with mannitol or lactose/MCC, as fillers.     

Functionality comparison of 3 classes of superdisintegrants in promoting aspirin tablet disintegration and dissolution

The aims of this study are (1) to compare the disintegration efficiency, and (2) to develop a discriminating test model for the 3 classes of superdisintegrants represented by Ac-Di-Sol, Primojel, and Polyplasdone XL10. Using a digital video camera to examine the disintegration process of tablets containing the same wt/wt percentage concentration of the disintegrants, Ac-Di-Sol was found to disintegrate tablets rapidly into apparently primary particles; Primojel also apparently disintegrated tablets into primary particles but more slowly; Polyplasdone XL10 disintegrated tablets rapidly but into larger masses of aggregated particles. The differences in the size distribution generated in the disintegrated tablets likely contribute to the drug dissolution rate differences found for aspirin tablets with similar disintegration rates. The aspirin tablet matrix is proposed as a model formulation for disintegrant efficiency comparison and performance consistency testing for quality control purposes. Published: December 12, 2005     

Evaluation of Citrus Fibers as a Tablet Excipient

The consumption of fibers is associated with many health benefits, such as a reduction of cardiovascular and gastrointestinal diseases, control of body weight, and prevention of diabetes. Despite the widespread use of fiber supplements such as capsules or tablets, there is an almost complete lack of information concerning the technological properties of functional fibers used in nutraceutical formulations. The aim of this work was to characterize the technological properties of citrus fibers necessary for their use as a processing aid in tableting. The results obtained showed that citrus fibers share many properties of other polysaccharides used as tableting excipients, such as thermal behavior and compaction mechanism, together with an appreciable tabletability. However, the most interesting properties resulted from their disintegration power. Citrus fibers behaved in a similar manner to the well-known super disintegrant croscarmellose sodium and resulted to be little susceptible to their concentration, to lubricant type, and lubricant concentration. Thus, this work supports the idea of a potential use of citrus fibers as “active” substances and processing aid in the tableting of nutraceutical products and also as functional excipient in pharmaceutical tablets formulation.     

Disintegration of Highly Soluble Immediate Release Tablets: A Surrogate for Dissolution

The purpose of the work was to investigate correlation between disintegration and dissolution for immediate release tablets containing a high solubility drug and to identify formulations where disintegration test, instead of the dissolution test, may be used as the acceptance criteria based on International Conference on Harmonization Q6A guidelines. A statistical design of experiments was used to study the effect of filler, binder, disintegrating agent, and tablet hardness on the disintegration and dissolution of verapamil hydrochloride tablets. All formulation variables, i.e., filler, binder, and disintegrating agent, were found to influence tablet dissolution and disintegration, with the filler and disintegrating agent exerting the most significant influence. Slower dissolution was observed with increasing disintegration time when either the filler or the disintegrating agent was kept constant. However, no direct corelationship was observed between the disintegration and dissolution across all formulations due to the interactions between different formulation components. Although all tablets containing sodium carboxymethyl cellulose as the disintegrating agent, disintegrated in less than 3 min, half of them failed to meet the US Pharmacopeia 30 dissolution criteria for the verapamil hydrochloride tablets highlighting the dependence of dissolution process on the formulation components other than the disintegrating agent. The results identified only one formulation as suitable for using the disintegration test, instead of the dissolution test, as drug product acceptance criteria and highlight the need for systematic studies before using the disintegration test, instead of the dissolution test as the drug acceptance criteria. The opinions expressed in this work are only of authors and do not necessarily reflect the policy and statements of the FDA.     

Development and Evaluation of Cetirizine HCl Taste-Masked Oral Disintegrating Tablets

The purpose of the current study was to mask the taste of cetirizine HCl and to incorporate the granules produced in oral disintegrating tablets (ODT). The bitter, active substance was coated by fluidized bed coating using Eudragit® RL30-D at levels between 15% and 40% w/w. The ODTs were developed by varying the ratio of superdisintegrants such as sodium croscarmellose, crospovidone grades and low substituted hydroxypropyl cellulose (L-HPC). A direct compression process was used to compress the ODTs under various compaction forces to optimize tablet robustness. The properties of the compressed tablets including porosity, hardness, friability and dissolution profiles were further investigated. The in vitro and in vivo evaluation of the tablet disintegration times showed almost identical rapid disintegration below 10 s at the optimal levels of each superdisintegrant. Finally, the taste and sensory evaluation in human volunteers demonstrated excellence in masking the bitter active and tablet palatability.     

A Novel Approach to Optimize and Formulate Fast Disintegrating Tablets for Nausea and Vomiting

The aim of this study was to optimize and formulate fast disintegrating tablets (FDTs) for nausea and vomiting using aminoacetic acid, carmellose and sodium alginate with enough mechanical strength. Ondansetron HCl (water soluble) or domperidone (water insoluble) drug were added to FDTs and their disintegration behaviour was evaluated. Plackett Burman Screening Design was used to screen the independent active process variables [concentration of aminoacetic acid (X ₁), concentration of carmellose (X ₂) and tablet crushing strength (X ₃)] which were found to actively influence the dependent variables [disintegration time in the mouth (DT), wetting time (WT), and water absorption ratio (WAR)] for both the drugs. Also, the coefficients of active variables (DT, WT and WAR) of FDTs containing domperidone was found to be significantly different (P < 0.05) from the coefficients of active factors (X ₁, X ₂ and X ₃) containing ondansetron HCl FDTs. Further, FDTs containing domperidone was prepared according to central composite design for estimating the effect of active factors (X ₁, X ₂, X ₃) in extended spherical domain. The regression analysis of quadratic fit revealed that DT, WT and WAR were 98% correlated with active factors (X ₁, X ₂ or X ₃). The optimized domperidone FDTs were further compared with superdisintegrants (croscarmellose sodium or crospovidone). The data revealed that optimized domperidone FDTs were better than domperidone FDTs containing croscarmellose or crospovidone. Hence, this novel excipients combination can be used for delivery of water insoluble drugs in place of superdisintegrants.     

Preparation and Application of Carboxymethyl Yam (Dioscorea esculenta) Starch

Yam (Dioscorea esculenta) starch was modified by carboxymethylation. The effect of reaction parameters, amount of sodium hydroxide (NaOH), amount of sodium monochloroacetate (SMCA), and reaction time on the degree of substitution (DS) of carboxymethyl yam starch (CMS), was studied using the Box–Behnken experimental design. Physicochemical and potency to be a tablet disintegrant of CMS were evaluated. CMS with DS in the range of 0.08–0.19 were obtained. The results from regression analysis indicated that the most important factor in controlling DS was the amount of NaOH followed by SMCA content and reaction time. However, high concentration of NaOH and SMCA lowered the DS. The optimal conditions to achieve the highest DS (0.19) were found to be at molar ratios of NaOH and SMCA to anhydroglucose unit of 1.80 and 2.35, respectively, and with the reaction time of 4.8 h. The swelling power and viscosity of CMS increased with an increase in the degree of modification. CMS showed satisfying tablet disintegrant properties. The tablets containing 1.0–4.0 % CMS disintegrated faster than 5 min. Hence carboxymethyl yam starch can be used as an excellent tablet disintegrant in low concentration.     

Microwave-Assisted Development of Orally Disintegrating Tablets by Direct Compression

Orally disintegrating tablets (ODTs) are challenged by the need for simple technology to ensure good mechanical strength coupled with rapid disintegration. The objective of this work was to evaluate microwave-assisted development of ODTs based on simple direct compression tableting technology. Placebo ODTs comprising directly compressible mannitol and lactose as diluents, super disintegrants, and lubricants were prepared by direct compression followed by exposure to >97% relative humidity and then microwave irradiation for 5 min at 490 W. Placebo ODTs with hardness (>5 kg/cm²) and disintegration time (<60 s) were optimized. Palatable ODTs of Lamotrigine (LMG), which exhibited rapid dissolution of LMG, were then developed. The stability of LMG to microwave irradiation (MWI) was confirmed. Solubilization was achieved by complexation with beta-cyclodextrin (β-CD). LMG ODTs with optimal hardness and disintegration time (DT) were optimized by a 2³ factorial design using Design Expert software. Taste masking using sweeteners and flavors was confirmed using a potentiometric multisensor-based electronic tongue, coupled with principal component analysis. Placebo ODTs with crospovidone as a superdisintegrant revealed a significant increase in hardness from ～3 to ～5 kg/cm² and a decrease in disintegration time (<60 s) following microwave irradiation. LMG ODTs had hardness >5 kg/cm², DT?<?30s, and rapid dissolution of LMG, and good stability was optimized by DOE and the design space derived. While β-CD complexation enabled rapid dissolution and moderate taste masking, palatability, which was achieved including flavors, was confirmed using an electronic tongue. A simple step of humidification enabled MWI-facilitated development of ODTs by direct compression presenting a practical and scalable advancement in ODT technology.     

Acid-treated yeast cell wall as a binder displaying function of disintegrant

This investigation examined the application of acid-treated yeast cell wall (AYC) as a binder functioning as a disintegrant. Acetylsalicylic acid (ASA) was granulated with AYC, hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), or pullulan (PUL) and compressed into a tablet in the absence of disintegrant. Particle size and angle of repose of the granules, tensile strength, disintegration time, and water absorption behavior of the tablets and ASA release profiles from the tablets were measured. The surface of AYC-granules was observed with a scanning electron microscope. As was the case with the granules of HPC, PVP, or PUL, D50 of the granules of AYC increased with increasing AYC addition percentage, indicating that it is possible to granulate ASA with AYC. Tablets incorporating HPC, PVP, and PUL failed to disintegrate within 30 minutes at all percentages of binder addition because in the case of the HPC, PVP, or PUL tablets in the dissolution medium, water scarcely penetrated into the inner region of the tablet, causing no disintegration. In the case of the AYC tablets, disintegration was not detected at 3% or less of AYC. When AYC was equal to or greater than 5%, AYC tablets disintegrated in approximately 4 minutes and rapid ASA release from the tablets was observed. These results may have been caused by the following. In the case of the AYC 3% granules, ungranulated aspirin powder remained, but in the case of the AYC 5% granules, ASA powder was granulated and covered with AYC. Water absorption was observed initially; however, a plateau was reached in the case of the AYC 3%-tablet. In contrast, in the cases of the AYC 5% and more tablets, water absorption was greater and increased with time. The angle of repose of the AYC 5% granules was 25.7°, which represented high fluidity. The tablets produced by compressing the granules demonstrated sufficient tensile strength greater than 0.8 MPa. The tablets rapidly disintegrated and rapid ASA release was obtained. AYC functioned as a binder at granulation; additionally, AYC served as a disintegrant in the dissolution of drug from the tablets. These results indicate that AYC affords high utility as a unique pharmaceutical additive possessing contrary functions such as binding and disintegration.