Tablet Disintegration Research Articles

Specific surface area of mannitol rather than particle size dominant the dissolution rate of poorly water-soluble drug tablets: A study of binary mixture

The dissolution behavior of tablets, particularly those containing poorly water-soluble drugs, is a critical factor in determining their absorption and therapeutic efficacy. Traditionally, the particle size of excipients has been considered a key property affecting tablet dissolution. However, lurasidone hydrochloride (LH) tablets prepared by similar particle size mannitol, namely M200 (D90 = 209.68 ± 1.42 μm) and 160C (D90 = 195.38 ± 6.87 μm), exhibiting significant differences in their dissolution behavior. In order to find the fundamental influential factors of mannitol influencing the dissolution of LH tablets, the properties (particle size, water content, true density, bulk density, tapped density, specific surface area, circularity, surface free energy, mechanical properties and flowability) of five grades mannitol including M200 and 160C were investigated. Principal component analysis (PCA) was used to establish a relationship between mannitol properties and the dissolution behavior of LH. The results demonstrated that specific surface area (SSA) emerged as the key property influencing the dissolution of LH tablets. Moreover, our investigation based on the percolation theory provided further insights that the SSA of mannitol influences the probability of LH-LH bonding and LH infinite cluster formation, resulting in the different percolation threshold states, then led to different dissolution behaviors. Importantly, it is worth noting that these findings do not invalidate previous conclusions, as reducing particle size generally increases SSA, thereby affecting the percolation threshold and dissolution behavior of LH. Instead, this study provides a deeper understanding of the underlying role played by excipient SSA in the dissolution of drug tablets. This study provides valuable guidance for the development of novel excipients aimed at improving drug dissolution functionality.

Mouth Dissolving Tablet Review

Mouth Dissolving Tablet Review

Amorphous solid dispersion of a binary formulation with felodipine and HPMC for 3D printed floating tablets

This study focuses on the combination of three-dimensional printing (3DP) and amorphous solid dispersion (ASD) technologies for the manufacturing of gastroretentive floating tablets. Employing hot melt extrusion (HME) and fused deposition modeling (FDM), the study investigates the development of drug-loaded filaments and 3D printed (3DP) tablets containing felodipine as model drug and hydroxypropyl methylcellulose (HPMC) as the polymeric carrier. Prior to fabrication, solubility parameter estimation and molecular dynamics simulations were applied to predict drug-polymer interactions, which are crucial for ASD formation. Physical bulk and surface characterization complemented the quality control of both drug-loaded filaments and 3DP tablets. The analysis confirmed a successful amorphous dispersion of felodipine within the polymeric matrix. Furthermore, the low infill percentage and enclosed design of the 3DP tablet allowed for obtaining low-density systems. This structure resulted in buoyancy during the entire drug release process until a complete dissolution of the 3DP tablets (more than 8 h) was attained. The particular design made it possible for a single polymer to achieve a zero-order controlled release of the drug, which is considered the ideal kinetics for a gastroretentive system. Accordingly, this study can be seen as an advancement in ASD formulation for 3DP technology within pharmaceutics.

Predicting gastric emptying of drug substances taken under postprandial conditions by combination of biorelevant dissolution and mechanistic in silico modeling

Physiologically based pharmacokinetic (PBPK) models can help to understand the effects of gastric emptying on pharmacokinetics and in particular also provide a platform for understanding mechanisms of food effects, as well as extrapolation between different postprandial conditions, whether standardized clinical or patient-oriented, non-clinical conditions. By integrating biorelevant dissolution data from the GastroDuo dissolution model into a previously described mechanistic model of fed-state gastric emptying, we simulated the effects of a high-calorie high-fat meal on the pharmacokinetics of sildenafil, febuxostat, acetylsalicylic acid, theobromine and caffeine. The model was able to simulate the variability in Cmax and tmax caused by the presence of the stomach road. The main influences investigated to affect the gastric emptying process were drug solubility (theobromine and caffeine), tablet dissolution rate (acetylsalicylic acid) and sensitivity to gastric motility (sildenafil and febuxostat). Finally, we showed how PBPK models can be used to extrapolate pharmacokinetics between different prandial states using theobromine as an example with results from a clinical study being presented.

The Formulation And Evaluation Of Metamizole Na Tablet With Porang Tubers(Amorphophallus Oncophyllus) Flour As A Binder

Many farmers are interested in planting porang tubers, and with many farmers planting porang tubers, the price of porang tubers has decreased at harvest time. Porang tubers contain several ingredients: starch, Glucomannan, fibre, fat, protein, minerals and vitamins. Glucomannan content can be used as a tablet binder, thickener, gelling agent, film former, coating material emulsifier, and stabilizer. This study used the wet granulation method to determine the concentration of porang tuber flour as a binder in Metamizole Na tablets. Tablets were made into three formulations with varying concentrations of porang tuber flour, namely FI 5%, FII 7.5% and FIII 10%. Tablets were tested for tablet uniformity, hardness, friability, disintegration time, and dissolution. The data obtained were analyzed using Kruskal Wallis. The analysis showed that variations in the concentration of porang tuber flour had a different effect, based on the Kruskal Wallis analysis, which showed a significant value of 0.10 (p>0.05). The formulation with a good physical quality test is formulation III, with a tablet hardness value of 6.84 kg and a disintegration time of 5.74 minutes, almost close to the control (+) 14.27 kg and 6.38 minutes. The higher the concentration of porang tuber flour, the higher the tablet hardness and the longer the disintegration and dissolution time.

Fast dissolving tablet

Fast dissolving tablets have emerged as a popular dosage form, particularly beneficial for pediatric and geriatric patients facing challenges such as dysphagia or hand tremors. These tablets dissolve quickly in saliva without needing water, enhancing compliance and effectiveness of therapy. They offer advantages like easy portability, accurate dosing, and improved bioavailability. Various technologies, including spray drying and melt granulation, have been developed for their manufacturing. This review provides comprehensive information on fast dissolving tablets, covering their definition, advantages, limitations, challenges, and available formulations. The design of an oral drug delivery system prioritizes convenience in administration and improved patient compliance, making it the preferred route of drug delivery despite certain drawbacks. Over the last decade, there has been a growing demand for Fast Disintegrating Tablets (FDTS), turning this field into a rapidly expanding area within the pharmaceutical industry. The formulation’s popularity and effectiveness have led to the development of various FDT technologies. These technologies aim to achieve rapid tablet disintegration and mouth dissolution within five seconds, eliminating the need for chewing or water intake. This characteristic is particularly advantageous for populations such as pediatrics, geriatrics, and patients facing difficulties in swallowing conventional tablets and capsules. The formulation of an easily administrable dosage form, considering challenges like swallowing difficulties and low patient compliance, has driven the creation of orally disintegrating tablets. Traditional preparation methods include spray drying, freeze drying, direct compression, molding, and sublimation. In addition, new technologies have been devised to enhance the production of orodispersible tablets.

Formulation and evaluation of nifedipine fast dissolving tablets

The current study aims to formulate and evaluate the fast-dissolving tablet. The optimal concentration of Guar gum super disintegrate was found to be 20 mg, with a disintegration time of 27 seconds. This study assessed the disintegration time of tablets containing natural super disintegrant for the Disintegration test at various weight concentrations (6,8,10,12,14,16,18, and 20 mg). As a result, the Nifedipine fast dissolving tablets with Guar gum super disintegrant provide a quick therapeutic effect, a high dissolve rate, and a shorter disintegration time. In this study, the use of a natural (guar gum) super disintegrating agent increases the rate of dissolution as well as length of disintegration of fast-dissolving tablets. In vitro drug release of 96% is demonstrated in 6 minutes with a disintegrating efficiency of 27 seconds for Nifedipine FDTs (guar gum). Consequently, our study has shown that formulations made with a natural super disintegrating agent exhibit shorter disintegration times as well as higher rates of dissolution along with drug release.

Manufacturing process transfer to a 30 kg/h continuous direct compression line with real-time composition monitoring

Transferring an existing marketed pharmaceutical product from batch to continuous manufacturing (CM) without changes in regulatory registration is a challenging task in the pharmaceutical industry. Continuous manufacturing can provide an increased production rate and better equipment utilisation while retaining key quality attributes of the final product. Continuous manufacturing necessitates the monitoring of critical quality attributes in real time by appropriate process analytical tools such as near infra-red (NIR) probes. The present work reports a successful transfer of an existing drug product from batch to continuous manufacturing process without changing the formulation. A key step was continuous powder blending, whose design and operating parameters including weir type, agitation rate, dynamic hold-up and residence time were systematically investigated with respect to process repeatability. A NIR-based multivariate data model for in-line composition monitoring has been developed and validated against an existing quality control method for measuring tablet content uniformity. A continuous manufacturing long-run with a throughput of 30 kg/h (approx. 128,000 tablets per hour), uninterrupted for 320 min, has been performed to test and validate the multivariate data model as well as the batch to continuous process transfer. The final disintegration and dissolution properties of tablets manufactured by the continuous process were found to be equivalent to those manufactured by the original batch process.

Quality Assurance and In-vitro Bioequivalence Analysis of Amlodipine Besylate Tablets

The proliferation of generic brands in the local pharmaceutical market makes it increasingly difficult for health professionals and patients to choose the optimal drug. The study aimed to assess the physicochemical parameters of generic amlodipine besylate tablets utilizing in-vitro testing to eliminate health hazards and maximize safety. Five brands (A, B, C, D, and E) of amlodipine besylate tablets (5 mg) were examined for six in-vitro tests; thickness, hardness, friability, uniformity of weight, disintegration, dissolution, and thin layer chromatography (TLC). The dissolution test revealed that Brand D had the highest percentage of drug release at 5 minutes (106.2%), followed by Brand E (103.2%), A (70.7%), B (64.4%), and C (61.0%), respectively. The spectrophotometric measurement was carried out at 240 nm. All five brands satisfied the British Pharmacopeia standard for uncoated tablet weight homogeneity (less than 5% variance) and disintegration within 15 minutes. Brand A has the longest disintegration time (4.37 minutes), whereas Brand B has the shortest (3.05). Brand E had the maximum hardness of 8.7 kg/cm², and Brand B had the lowest hardness of 3 kg/cm². All five brands had a friability percentage of less than 1%, with bread B having the highest (0.91%) and brand E, lowest (0.10%), all tablets crumbled after 15 minutes. All brands passed the quality assessment test. Conclusion: The Quality Assurance and in-vitro bioequivalence assay methods used in this study are dependable, simple, and inexpensive, and they can be used consistently to evaluate amlodipine tablets and other solid-dosage pharmaceutical products.

A review on tablet binders as a pharmaceutical excipient

The tablet formulation contains binders that increase the inter-particulate bond power inside the tablet. Research and progress of novel accessories remains a priority for potential use as a binder in formulations tablet. Tablet binder or binding agent are the substances that are added either dry or in liquid form during wet granulation to form granules or to promote cohesive compacts for directly compressed tablets. E.g., starch, pregelatinized starch, PEG, sorbitol, and HPMC, etc. Tablet Binder and disintegrants have the opposite used in an oral solid formulation. Binder delay tablet disintegration while disintegrant increase tablet disintegration. They play a vital role in making sure pellets or granules and tablets remain in shape until they reach their target by holding all ingredients (API and Excipients) together in any solid dosage form. Selecting the correct binder is critical to maintaining the integrity of the tablet. Natural binders such as various starches, Gums, mucus and dried fruits, among other things, have the ability to bind. Features such as Natural polymers, fillers, and disintegrants are also safe more economical than synthetic polymers.

A prediction model based on artificial intelligence techniques for disintegration time and hardness of fast disintegrating tablets in pre-formulation tests

BackgroundThe pharmaceutical industry is continually striving to innovate drug development and formulation processes. Orally disintegrating tablets (ODTs) have gained popularity due to their quick release and patient-friendly characteristics. The choice of excipients in tablet formulations plays a critical role in ensuring product quality, highlighting its importance in tablet creation. The traditional trial-and-error approach to this process is both expensive and time-intensive. To tackle these obstacles, we introduce a fresh approach leveraging machine learning and deep learning methods to automate and enhance pre-formulation drug design.MethodsWe collected a comprehensive dataset of 1983 formulations, including excipient names, quantities, active ingredient details, and various physicochemical attributes. Our study focused on predicting two critical control test parameters: tablet disintegration time and hardness. We compared a range of models like deep learning, artificial neural networks, support vector machines, decision trees, multiple linear regression, and random forests.ResultsA 12-layer deep neural network, as a form of deep learning, surpassed alternative techniques by achieving 73% accuracy for disintegration time and 99% for tablet hardness. This success underscores its efficacy in predicting complex pharmaceutical factors. Such an approach streamlines the drug formulation process, reducing iterations and material consumption.ConclusionsOur findings highlight the deep learning potential in pharmaceutical formulations, particularly for tablet hardness prediction. Future work should focus on enlarging the dataset to improve model effectiveness and extend its application in pharmaceutical product development and assessment.

Utilization and Evaluation of Rice Bran and Rice Bran Wax as a Tablet Lubricant.

The rice bran and rice bran wax of the KJ CMU107 rice strain were investigated as potential tablet lubricants in a directly compressed tablet formulation. Stabilized full-fatted rice bran (sFFRB), stabilized defatted rice bran (sDFRB), and rice bran wax (RBW) extracted and purified from crude rice bran oil (cRBO) were tested. Two commercial lubricants, including magnesium stearate (MGS) and hydrogenated cottonseed oil (HVO), were employed as the standards in the formulated mixtures, which contained spray-dried rice starch (SDRS) as a diluent. The tableting was carried out for each formulation, and the obtained tablets were physically and mechanically evaluated. Among the parameters investigated were the general appearance, ejection force, weight variation, hardness, friability, and disintegration time. The powder flow was also determined for each formulation. The results showed that the tablet ejection forces for all the lubricated formulations (58-259 N) were significantly lower than that of the non-lubricated control formulation (349 N). The use of sFFRB as a lubricant at 0.5-2.0% w/w could lower the ejection force up to 78%, but the hardness reduced so drastically that the formulations failed the friability test due to the chipping of the tablets' edges. Moreover, sDFRB performed significantly better as the use at 0.5-1.0% w/w in the formulation helped to lower the ejection forces by up to 80% while maintaining the changes in the tablet hardness within 10%. RBW functioned effectively as a tablet lubricant at a concentration of 0.5% w/w, yielding tablets with good strength comparable to standard HVO lubricant while helping to reduce the ejection force by 82%. In formulations with good lubrication, i.e., friability < 1%, the powder flow was improved, and the tablet disintegration times were within the same range as the control and HVO formulations. In conclusion, sDFRB displayed a lubricant property at concentrations between 0.5 and 1.0% w/w, with slightly negative effects on the tablet hardness. RBW from KJ CMU107 rice was an effective tablet lubricant at 0.5% w/w, with no effect on tablet hardness. Both materials can be further developed for use as commercial lubricants in direct compression.

Medication Lubricants for Oral Delivery of Drugs: Oral Processing Reduces Thickness, Changes Characteristics, and Improves Dissolution Profile.

Swallowing oral solid dosage forms is challenging for those who have medication swallowing difficulties, including patients with dysphagia. One option is to mix the drug (whole or crushed) with a thick vehicle (medication lubricant). Previous in vitro studies consistently suggest that thick vehicles could impact the dissolution of solid dosage forms, potentially influencing their therapeutic effectiveness, but do not account for changes that happen during oral processing and swallowing. This study aims to investigate the potential impact of medication lubricants on drug release and examine the effect of oral processing. In vitro dissolution of whole and crushed paracetamol tablets mixed with five commercially available medication lubricants (two IDDSI level 2, two IDDSI level 3, and one IDDSI level 4) were tested with and without oral processing; a medication lubricant with/without paracetamol was placed in the mouth (five healthy volunteers), prepared for swallowing, but then expectorated and assessed for physical characteristics and drug release. Medication lubricants, both alone and mixed with crushed paracetamol tablets, showed a significant decrease in viscosity after oral processing. Without oral processing, IDDSI level 3 and 4 lubricants significantly delayed the dissolution of paracetamol tablets. After oral processing, particularly with crushed tablets, there was a substantial increase in the dissolution rate. These findings suggest that dissolution testing overestimates the impact of medication lubricants on drug dissolution. Therefore, using in vitro dissolution tests to predict the dissolution rate of medications mixed with thick vehicles is discouraged. It is essential to consider ways to incorporate the effects of the oral environment and oral processing on thick vehicles used for oral medication administration.

Machine vision-based non-destructive dissolution prediction of meloxicam-containing tablets

Machine vision systems have emerged for quality assessment of solid dosage forms in the pharmaceutical industry. These can offer a versatile tool for continuous manufacturing while supporting the framework of process analytical technology, quality-by-design, and real-time release testing. The aim of this work is to develop a digital UV/VIS imaging-based system for predicting the in vitro dissolution of meloxicam-containing tablets. The alteration of the dissolution profiles of the samples required different levels of the critical process parameters, including compression force, particle size and content of the API. These process parameters were predicted non-destructively by multivariate analysis of UV/VIS images taken from the tablets. The dissolution profile prediction was also executed using solely the image data and applying artificial neural networks. The prediction error (RMSE) of the dissolution profile points was less than 5%. The alteration of the API content directly affected the maximum concentrations observed at the end of the dissolution tests. This parameter was predicted with a relative error of less than 10% by PLS models that are based on the color components of UV and VIS images. In conclusion, this paper presents a modern, non-destructive PAT solution for real-time testing of the dissolution of tablets.

CELLULOSE NANOCRYSTAL-INCORPORATED CO-PROCESSED EXCIPIENT IN TABLET FORMULATION

The objective of the current work is to develop a new co-processed excipient based on cellulose nanocrystals and investigate its pharmaceutical excipient properties. Cellulose nanocrystals were isolated from the pseudostem of Musa balbisiana, following TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy)-mediated oxidation, and then co-processed with potato starch by the wet granulation method. Physicochemical properties, including the flow property, consolidation characteristics and rate of consolidation, were investigated, and a Kawakita plot was also generated. The compressibility, compactibility and tabletability of the novel excipient were determined. The equivalent circle diameter of the excipient particle was calculated as 4.09±0.90 μm, exhibiting a fair to passable flow property. The mean yield pressure from the Heckel plot was found to be 82.64 MPa, indicating its ability to undergo plastic deformation at relatively lower compression pressures. When compared to sodium starch glycolate, a standard tablet disintegrant, the cellulose nanocrystal-based co-processed excipient produced better dissolution of the model drug paracetamol.

The Effect of Formulation Variables on the Manufacturability of Clopidogrel Tablets via Fluidized Hot-Melt Granulation-From the Lab Scale to the Pilot Scale.

Solid pharmaceutical formulations with class II active pharmaceutical ingredients (APIs) face dissolution challenges due to limited solubility, affecting in vivo behavior. Robust computational tools, via data mining, offer valuable insights into product performance, complementing traditional methods and aiding in scale-up decisions. This study utilizes the design of experiments (DoE) to understand fluidized hot-melt granulation manufacturing technology. Exploratory data analysis (MVDA) highlights similarities and differences in tablet manufacturability and dissolution profiles at both the lab and pilot scales. The study sought to gain insights into the application of multivariate data analysis by identifying variations among batches produced at different manufacturing scales for this technology. DoE and MVDA findings show that the granulation temperature, time, and Macrogol type significantly impact product performance. These factors, by influencing particle size distribution, become key predictors of product quality attributes such as resistance to crushing, disintegration time, and early-stage API dissolution in the profile. Software-aided data mining, with its multivariate and versatile nature, complements the empirical approach, which is reliant on trial and error during product scale-up.

Preparation and Evaluation of Mouth Dissolving Tablet of Albendazole Using Different Concentrations of Super-Disintegrant

Anthelmintic medications are anticipated to act more quickly and have greater absorption. Mouth-dissolving albendazole tablets were created using a direct compression approach and a mixture of super disintegrants to accomplish rapid disintegration of the tablets in the oral cavity. The preparation of ten batches of mouth-dissolving tablets using different grades of Kollidon, crospovidone, sodium starch glycolate, and croscarmellose sodium as super disintegrants produced the greatest results. For a compatibility investigation, FTIR was used to characterize the drug and physical mixture. An optimization technique was used to forecast the most effective formulation out of all the prepared combinations. All the physical characteristics of the tablet are within the limit. All preformulation results indicated good flow properties. Disintegration time and drug content of the F4 batch were found to be 28 seconds and 95.69%, respectively. In vitro release of the drug was performed in a phosphorus buffer pH 6.8 for 40 min, in which F4 shows maximum drug release. Based on the stability studies, it was confirmed that the optimized formulation remained at accelerated stability conditions. It was discovered that the mouth-dissolving tablet exhibits effective drug release.

The impact of diluents on the compaction, dissolution, and physical stability of amorphous solid dispersion tablets

Amorphous solid dispersion (ASD) is an effective approach for enhancing the solubility, dissolution, and bioavailability of poorly water-soluble drugs. However, these metastable forms can transform into more thermodynamically stable but less soluble crystalline forms. Despite this challenge, research on processing ASDs into solid dosage forms, such as tablets, is lacking. This work aims to fill this gap by investigating the impact of common diluents on the tableting behavior, dissolution, and physical stability of ASDs composed of itraconazole and hypromellose acetate succinate. Four widely used diluents found in commercially available ASD tablets were selected for the study: microcrystalline cellulose (MCC), anhydrous lactose, starch, and mannitol. The performance of ASD tablets varied significantly depending on the diluent used. Tablets prepared with MCC exhibited higher mechanical strength than those formulated using other diluents. ASD tablets containing mannitol and lactose revealed a faster release rate than those composed of MCC or starch. Notably, the study highlighted that the physical stability of ASDs within a tablet is not solely dependent on the amount of sorbed water; crystalline diluents like lactose and mannitol were found to facilitate ASD recrystallization within a tablet. In summary, the study underscores the importance of excipient selection, considering factors such as mechanical strength, dissolution rate, and physical stability of ASD tablets. These findings offer valuable insights into the selection of excipients for downstream ASD tablet development, leading to improved manufacturability, physical stability, and the overall quality of ASD drug products.

Preparation and Evaluation of Carboxymethylated Dioscorea bulbifera Starch as Disintegrant in Ibuprofen Oral Tablet

Preparation and Evaluation of Carboxymethylated Dioscorea bulbifera Starch as Disintegrant in Ibuprofen Oral Tablet

Cushion-coated pellets for tableting without external excipients

Multiple-unit dosage forms prepared by compacting pellets offer important manufacturing and compliance advantages over pellet-filled capsules. However, compaction may negatively affect the release control mechanism of pellets, and subunits may not be readily available after intake. Application of a cushioning layer to the starting units is here proposed as a strategy to obtain tablets with satisfactory mechanical strength, rapid disintegration and maintenance of the expected release profile of individual subunits while avoiding the use of mixtures of pellets and excipients to promote compaction and limit the impact of the forces involved. Cushion-coating with PEG1500, a soft and soluble material, was proved feasible provided that the processing temperature was adequately controlled. Cushioned gastro-resistant pellets were shown to consolidate under relatively low compaction pressures, which preserved their inherent release performance after tablet disintegration. Adhesion problems associated with the use of PEG1500 were overcome by applying an outer Kollicoat® IR film. Through design of experiment (DoE), robustness of the proposed approach was demonstrated, and the formulation as well as tableting conditions were optimized. The tableted cushion-coated pellet systems manufactured would allow a relatively high load of modified-release units to be conveyed, thus setting out a versatile and scalable approach to oral administration of multiple-unit dosage forms.