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In this study, a compartmental disintegration and dissolution model is proposed for the prediction and evaluation of the dissolution performance of directly compressed tablets. This dissolution model uses three compartments (Bound, Disintegrated, and Dissolved) to describe the state of each particle of active pharmaceutical ingredient. The disintegration of the tablet is captured by three fitting parameters. Two disintegration parameters, ß0 and ßt,0, describe the initial disintegration rate and the change in disintegration rate, respectively. A third parameter, α, describes the effect of the volume of dissolved drug on the disintegration process. As the tablet disintegrates, particles become available for dissolution. The dissolution rate is determined by the Nernst-Brunner equation, whilst taking into account the hydrodynamic effects within the vessel of a USP II (paddle) apparatus. This model uses the raw material properties of the active pharmaceutical ingredient (solubility, particle size distribution, true density), lending it towards early development activities during which time the amount of drug substance available may be limited. Additionally, the strong correlations between the fitting parameters and the tablet porosity indicate the potential to isolate the manufacturing effects and thus implement the model as part of a real-time release testing strategy for a continuous direct compression line.
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Liberación de Fármacos , Tamaño de la Partícula , Solubilidad , Comprimidos , Porosidad , Composición de Medicamentos/métodos , Química Farmacéutica/métodos , Excipientes/química , Modelos QuímicosRESUMEN
Controlling environmental effects in surface plasticity/fracture of metals is of interest for areas as diverse as manufacturing processes, product performance, and structural safety. The key to controlling these effects is understanding the effect of adsorbates on surface energy (γ) and surface stress (f). While γ has been well studied, the role of surface stress has received much less attention. We characterize surface stress induced in metals by adsorption of organic monolayers. Linear alkanoic acids of varying chain length (3-18) are deposited by molecular self-assembly onto one side of an aluminum cantilever, several centimeters in length. The surface stress is estimated from in situ measurement of the cantilever deflection. We find that the organic adsorbates induce large surface stress of -4 to +30N/m. Furthermore, we show that f may be tuned by varying adsorbate-molecule chain length. The stress data explain beneficial embrittlement of metal surfaces by organic adsorbates in cutting and comminution processes, and point to a critical role, hitherto ignored, for f in environment assisted cracking (EAC) phenomena. Our results suggest opportunities for utilizing controlled environment-assisted fracture as an aid-fracture as a friend-to enhance material removal processes, apart from using surface stress itself as an experimental probe to explore various manifestations of EAC.
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Dissolution of ionizable drugs and their salts is a function of drug surface solubility driven by the surface pH, i.e., the microenvironmental pH at the solid/liquid interface, which will deviate from bulk pH when there is an acid-base reaction occurring at the solid/liquid interface. In this work, we first present a brief overview of the modeling approaches available in the literature, classified according to the rate-determining step assumed in the dissolution process. In the second part, we present and evaluate the prediction performance of two different modeling approaches for surface pH. The first method relies only on thermodynamic equilibria, while the second method accounts for transport phenomena of charged compounds through the diffusional boundary layer using the Nernst - Planck equation. Model outcomes are compared with experimental data taken from the literature and obtained during this work. In terms of surface pH predictions, the models provide identical values for weak acids or weak bases. The models' outcomes for bases are in good agreement with experimental data in acidic conditions (bulk pH 1-4), while overpredictions are observed in the 5-7 bulk pH range in a system-dependent manner. Deviations can be related to the effect of surface dissolution (also referred to as surface reaction), which may become a controlling mechanism and slow the replenishment of the unionized drug at the surface of the crystal. Surface pH predictions for acids are generally in good agreement with experiments, with a slight underestimation for some drug examples, which could be related to errors in intrinsic solubility determination or to the assumption of thermodynamic equilibrium at the surface of the drug. A good agreement is also observed for salts with the thermodynamic model except for mesylate salts, suggesting that other phenomena, not currently included in the thermodynamic equilibrium model, may determine the surface pH.
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Sales (Química) , Concentración de Iones de Hidrógeno , Difusión , SolubilidadRESUMEN
Nanomedicines have emerged as a promising approach for targeted therapeutic delivery and specifically as a beneficial alternative to conventional cancer therapies as they can deliver higher concentrations of chemotherapeutic agents at the tumour site compared to healthy tissue, thus providing improved drug efficacy and lower systemic toxicity. Long acting injectables are increasingly becoming the focus of pharmaceutical research, as they can reduce dosing frequency and improve the life quality of patients. Development of an in vitro release (IVR) method for modified release nanomedicines is challenging because of the uniqueness and range of different formulation design approaches, as well as the complex nature of drug release mechanisms which may result in inherent variability. Regulatory guidance on the development of dissolution or release methods for parenteral products is limited relative to oral products. This article details the extensive in vitro release method development work conducted on a polymeric nanoparticle to develop the release media composition and selection of suitable apparatus and sampling technique to separate the released drug from the formulation. The aim was to develop a suitably robust analytical method that generated clinically relevant in vitro release data.
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Química Farmacéutica , Nanopartículas , Humanos , Química Farmacéutica/métodos , Preparaciones Farmacéuticas , Liberación de Fármacos , Nanomedicina , Sistemas de Liberación de MedicamentosRESUMEN
Acalabrutinib maleate tablets correspond to an improved formulation compared to acalabrutinib capsules as they can be dosed with and without acid reducing agents and therefore benefit more cancer patients. The dissolution specification for the drug product was determined using all the information available on the drug safety, efficacy, and in vitro performance. In addition, a physiologically based biopharmaceutics model was developed for acalabrutinib maleate tablets on the back of a previously published model for acalabrutinib capsules to establish that the proposed drug product dissolution specification would ensure safe and effective products for all patients including those under acid reducing agent treatment. The model was built, validated, and used to predict the exposure of virtual batches where the dissolution was slower than that of the clinical target. A combination of exposure prediction and the use of a PK-PD model allowed it to be demonstrated that the proposed drug product dissolution specification was acceptable. This combination of models enabled a larger safe space than would have been granted by consideration of bioequivalence only.
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Biofarmacia , Modelos Biológicos , Humanos , Solubilidad , Cápsulas , Equivalencia Terapéutica , Comprimidos , MaleatosRESUMEN
Importance: Ibrutinib has been associated with serious cardiotoxic arrhythmias. In preclinical models, these events are paralleled or proceeded by diffuse myocardial injury (inflammation and fibrosis). Yet whether this is seen in patients or has implications for future cardiotoxic risk is unknown. Objective: To assess the incidence and outcomes of myocardial injury among patients with ibrutinib-related cardiotoxicity. Design, Setting, and Participants: This cohort study included consecutive patients treated with ibrutinib from 2012 to 2019, phenotyped using cardiovascular magnetic resonance (CMR) from a large US Comprehensive Cancer Center registry. Exposures: Ibrutinib treatment for cancer control. Main Outcomes and Measures: The primary outcome was the presence of late gadolinium enhancement (LGE) fibrosis. The secondary outcome was the occurrence of major adverse cardiac events (MACE), defined as atrial fibrillation, heart failure, symptomatic ventricular arrhythmias, and sudden death of probable or definite ibrutinib association after CMR. We also assessed parametric-mapping subclinical fibrosis (native-T1, extracellular volume fraction) and inflammation/edema (max-T2) measures. Cardiovascular magnetic resonance measures were compared with those obtained in similar consecutive patients with cancer without ibrutinib treatment (pretreatment controls). Observed measures were also compared with similar-aged broad population rates (general-population controls) and a broader pool of cardiovascular disease (CVD) risk-matched cancer controls. Multivariable regression was used to assess the association between CMR measures and MACE. Results: Overall, 49 patients treated with ibrutinib were identified, including 33 imaged after treatment initiation (mean [SD] age, 65 [10] years, 9 [27%] with hypertension, and 23 [69.7%] with index-arrhythmias); median duration of ibrutinib-use was 14 months. The mean (SD) pretreatment native T1 was 977.0 (73.0) ms, max-T2 56.5 (4.0) ms, and 4 (13.3%) had LGE. Posttreatment initiation, mean (SD) native T1 was 1033.7 (48.2) ms, max-T2 61.5 (4.8) ms, and 17 (54.8%) had LGE (P < .001, P = .01, and P < .001, respectively, pre- vs post-ibrutinib treatment). Native T12SDs was elevated in 9 (28.6%), and max-T22SDs in 21 (63.0%), respectively. Cardiovascular magnetic resonance measures were highest in those with suspected toxic effects (P = .01 and P = .01, respectively). There was no association between traditional CVD-risk or cancer-treatment status and abnormal CMR measures. Among those without traditional CVD, 16 (58.6%) had LGE vs 38 (13.3%) in matched-controls (relative-risk, 4.8; P < .001). Over a median follow-up of 19 months, 13 (39.4%) experienced MACE. In multivariable models inclusive of traditional CVD risk factors, LGE (hazard ratio [HR], 4.9; P = .04), and native-T12SDs (HR, 3.3; P = .05) associated with higher risks of MACE. Conclusions and Relevance: In this cohort study, myocardial injury was common in ibrutinib users, and its presence was associated with higher cardiotoxic risk.
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Medios de Contraste , Miocardio , Humanos , Anciano , Miocardio/patología , Estudios de Cohortes , Cardiotoxicidad/etiología , Imagen por Resonancia Cinemagnética , Gadolinio , Imagen por Resonancia Magnética/métodos , Fibrosis , Inflamación , Valor Predictivo de las Pruebas , Función Ventricular Izquierda , Pronóstico , Volumen SistólicoRESUMEN
During drug product development, stability studies are used to ensure that the safety and efficacy of a product are not affected during storage. Any change in the dissolution performance of a product must be investigated, as this may indicate a change in the bioavailability. In this study, three different griseofulvin formulations were prepared containing microcrystalline cellulose (MCC) with either mannitol, lactose monohydrate, or dibasic calcium phosphate anhydrous (DCPA). The tensile strength, porosity, contact angle, disintegration time, and dissolution rate were measured after storage under five different accelerated temperature and humidity conditions for 1, 2, and 4 weeks. The dissolution rate was found to decrease after storage for all three batches, with the change in dissolution rate strongly correlating with the storage humidity. The changes in physical properties of each formulation were found to relate to either the premature swelling (MCC/DCPA, MCC/lactose) or dissolution (MCC/mannitol) of particles during storage. These results are also discussed with consideration of the performance- and stability-controlling mechanisms of placebo tablets of the same formulations (Maclean et al., 2021; Maclean et al., 2022).
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Griseofulvina , Lactosa , Solubilidad , Lactosa/química , Comprimidos/química , ManitolRESUMEN
BACKGROUND: CRISPR-Cas based diagnostic assays provide a portable solution which bridges the benefits of qRT-PCR and serological assays in terms of portability, specificity and ease of use. CRISPR-Cas assays are rapidly fieldable, specific and have been rigorously validated against a number of targets, including HIV and vector-borne pathogens. Recently, CRISPR-Cas12 and CRISPR-Cas13 diagnostic assays have been granted FDA approval for the detection of SARS-CoV-2. A critical step in utilizing this technology requires the design of highly-specific and efficient CRISPR RNAs (crRNAs) and isothermal primers. This process involves intensive manual curation and stringent parameters for design in order to minimize off-target detection while also preserving detection across divergent strains. As such, a single, streamlined bioinformatics platform for rapidly designing crRNAs for use with the CRISPR-Cas12 platform is needed. Here we offer PrimedSherlock, an automated, computer guided process for selecting highly-specific crRNAs and primers for targets of interest. RESULTS: Utilizing PrimedSherlock and publicly available databases, crRNAs were designed against a selection of Flavivirus genomes, including West Nile, Zika and all four serotypes of Dengue. Using outputs from PrimedSherlock in concert with both wildtype A.s Cas12a and Alt-R Cas12a Ultra nucleases, we demonstrated sensitive detection of nucleic acids of each respective arbovirus in in-vitro fluorescence assays. Moreover, primer and crRNA combinations facilitated the detection of their intended targets with minimal off-target background noise. CONCLUSIONS: PrimedSherlock is a novel crRNA design tool, specific for CRISPR-Cas12 diagnostic platforms. It allows for the rapid identification of highly conserved crRNA targets from user-provided primer pairs or PrimedRPA output files. Initial testing of crRNAs against arboviruses of medical importance demonstrated a robust ability to distinguish multiple strains by exploiting polymorphisms within otherwise highly conserved genomic regions. As a freely-accessible software package, PrimedSherlock could significantly increase the efficiency of CRISPR-Cas12 diagnostics. Conceptually, the portability of detection kits could also be enhanced when coupled with isothermal amplification technologies.
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COVID-19 , Ácidos Nucleicos , Infección por el Virus Zika , Virus Zika , Sistemas CRISPR-Cas/genética , Humanos , ARN , SARS-CoV-2/genética , Virus Zika/genéticaRESUMEN
Acalabrutinib is a Bruton tyrosine kinase (BTK) inhibitor approved to treat adults with chronic lymphocytic leukemia, small lymphocytic lymphoma, or previously treated mantle cell lymphoma. As the bioavailability of the acalabrutinib capsule (AC) depends on gastric pH for solubility and is impaired by acid-suppressing therapies, coadministration with proton-pump inhibitors (PPIs) is not recommended. Three studies in healthy subjects (N = 30, N = 66, N = 20) evaluated the pharmacokinetics (PKs), pharmacodynamics (PDs), safety, and tolerability of acalabrutinib maleate tablet (AT) formulated with pH-independent release. Subjects were administered AT or AC (orally, fasted state), AT in a fed state, or AT in the presence of a PPI, and AT or AC via nasogastric (NG) route. Acalabrutinib exposures (geometric mean [% coefficient of variation, CV]) were comparable for AT versus AC (AUCinf 567.8 ng h/mL [36.9] vs 572.2 ng h/mL [38.2], Cmax 537.2 ng/mL [42.6] vs 535.7 ng/mL [58.4], respectively); similar results were observed for acalabrutinib's active metabolite (ACP-5862) and for AT-NG versus AC-NG. The geometric mean Cmax for acalabrutinib was lower when AT was administered in the fed versus the fasted state (Cmax 255.6 ng/mL [%CV, 46.5] vs 504.9 ng/mL [49.9]); AUCs were similar. For AT + PPI, geometric mean Cmax was lower (371.9 ng/mL [%CV, 81.4] vs 504.9 ng/mL [49.9]) and AUCinf was higher (AUCinf 694.1 ng h/mL [39.7] vs 559.5 ng h/mL [34.6]) than AT alone. AT and AC were similar in BTK occupancy. Most adverse events were mild with no new safety concerns. Acalabrutinib formulations were comparable and AT could be coadministered with PPIs, food, or via NG tube without affecting the PKs or PDs.
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Inhibidores de la Bomba de Protones , Pirazinas , Adulto , Humanos , Disponibilidad Biológica , Equivalencia Terapéutica , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/farmacocinética , Pirazinas/efectos adversos , Pirazinas/farmacocinética , Comprimidos , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacocinéticaRESUMEN
BACKGROUND: Unipolar electrograms (UniEGMs) are commonly used to annotate earliest local activation of focal arrhythmias. However, their utility in guiding premature ventricular contractions (PVCs) ablation may be limited when the PVC source is less superficial. OBJECTIVES: The authors sought to compare bipolar electrograms (BiEGMs) vs UniEGMs in guiding successful ablation of right ventricular outflow tract (RVOT) vs intramural outflow tract (OT) PVCs. The authors hypothesized that: 1) earliest bipolar local activation time (LATBi) would better guide mapping and ablation, vs UniEGM dV/dt (LATUni) or QS morphology; and 2) LAT differences using bipolar vs unipolar EGMs (ΔLATBi-Uni) would be greater for intramural OT than RVOT PVCs. METHODS: Consecutive patients undergoing successful PVC ablation 2017 to2020 requiring only RVOT or RVOT+left ventricular OT (RVOT+LVOT) ablation were retrospectively analyzed. BiEGMs and UniEGMs at successful ablation sites were compared. RESULTS: Of 70 patients, 50 required RVOT-only, and 20 required RVOT+LVOT ablation for acute and long-term PVC suppression. Mean ΔLATBi-Uni was lower for RVOT vs RVOT+LVOT groups (9.3 ± 6.4 ms vs 17.4 ± 9.9 ms; P < 0.01). QS UniEGM was seen in 78% of RVOT, compared with 53% of RVOT+LVOT patients (P < 0.016). RVOT+LVOT sites most frequently included the posteroseptal RVOT and adjacent LVOT (73%), and 43% lacked a QS unipolar EGM. ΔLATBi-Uni ≥15 ms best distinguished sites in which RVOT-only vs RVOT+LVOT ablation achieved acute PVC suppression (area under the curve: 0.77). CONCLUSIONS: Earliest BiEGM activation guides successful ablation of OT PVCs better than UniEGM-guided analysis, especially when an intramural PVC source is present.
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Ablación por Catéter , Taquicardia Ventricular , Complejos Prematuros Ventriculares , Humanos , Estudios Retrospectivos , Taquicardia Ventricular/cirugía , Resultado del Tratamiento , Complejos Prematuros Ventriculares/cirugíaRESUMEN
Aedes japonicus japonicus continues to spread westward and in this study, its presence is documented in 8 counties in Nebraska and in Bowie County, TX. In 1998, Ae. japonicus was collected in Connecticut, New Jersey, and New York for the 1st records of this species in North America. Except for Louisiana, it has been reported from all states that border or are east of the Mississippi River. In Canada, it has been reported in Ontario and all eastern provinces. In the Pacific Northwest, it has been reported in Washington, Oregon, and British Columbia, and in the midwestern states that do not border the Mississippi River, Kansas, Oklahoma, and South Dakota are the only states to have reported its presence in peer-reviewed journals.
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Aedes , Animales , Mississippi , Nebraska , Texas , WashingtónRESUMEN
AIMS: Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, is approved for the treatment of mantle cell lymphoma and chronic lymphocytic leukaemia. Many critically ill patients are unable to swallow and need oral medications to be delivered via a nasogastric (NG) tube. Furthermore, critically ill patients are typically administered proton-pump inhibitors (PPIs) to prevent stress ulcers. Concomitant administration with PPIs reduces acalabrutinib exposure and is not currently recommended. To evaluate acalabrutinib in subjects co-administered with PPIs who require NG delivery, a phase 1, open-label, randomized, crossover, single-dose study was conducted in healthy subjects. METHODS: The study assessed the relative bioavailability of an acalabrutinib suspension-in regular, degassed Coca-Cola-administered via NG tube (Acala-NG) versus the pharmacokinetics (PK) of an acalabrutinib capsule administered orally with water. In addition, the PPI effect was evaluated by comparing the PK following Acala-NG in the presence or absence of rabeprazole. RESULTS: Exposure of acalabrutinib and its active metabolite (ACP-5862) were comparable following administration of Acala-NG versus the oral capsule (Geo mean ratio, % ref [90% confidence interval, CI]: acalabrutinib AUCinf : 103 [93-113]; Cmax : 144 [120-173]). In addition, exposure was similar following administration of Acala-NG with and without a PPI (Geo mean ratio, % ref [90% CI]: acalabrutinib AUCinf : 105 [79-138]; Cmax : 95 [66-137]). No safety or tolerability concerns were observed, and all adverse events were mild and resolved without treatment. CONCLUSIONS: Acala-NG with or without a PPI is safe and well-tolerated without impeding bioavailability.
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Enfermedad Crítica , Inhibidores de la Bomba de Protones , Adulto , Benzamidas , Disponibilidad Biológica , Estudios Cruzados , Voluntarios Sanos , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/farmacocinética , Pirazinas , SuspensionesRESUMEN
Endovascular treatment of aortic disorders has gained wide acceptance due to reduced physiological burden to the patient compared to open surgery, and ongoing stent-graft evolution has made aortic repair an option for patients with more complex anatomies. To date, commercial stent-grafts are typically developed from established production techniques with simple design structures and limited material ranges. Despite the numerous updated versions of stent-grafts by manufacturers, the reoccurrence of device-related complications raises questions about whether the current manfacturing methods are technically able to eliminate these problems. The technology trend to produce efficient medical devices, including stent-grafts and all similar implants, should eventually change direction to advanced manufacturing techniques. It is expected that through recent advancements, especially the emergence of 4D-printing and smart materials, unprecedented features can be defined for cardiovascular medical implants, like shape change and remote battery-free self-monitoring. 4D-printing technology promises adaptive functionality, a highly desirable feature enabling printed cardiovascular implants to physically transform with time to perform a programmed task. This review provides a thorough assessment of the established technologies for existing stent-grafts and provides technical commentaries on known failure modes. They then discuss the future of advanced technologies and the efforts needed to produce next-generation endovascular implants.
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Implantación de Prótesis Vascular , Procedimientos Endovasculares , Prótesis Vascular , Humanos , Diseño de Prótesis , Stents , Resultado del TratamientoRESUMEN
Stability studies are an integral part of the drug development process for any drug product. In addition to monitoring chemical degradation, the physical stability of a drug product must also be evaluated to ensure that the drug release and performance is not affected by storage. In this study, directly compressed tablets of 16 different formulations were exposed to an accelerated stability program to quantify changes in tablet breaking force, porosity, contact angle and disintegration time. Tablets were exposed to five different storage conditions from 37∘ C/30% relative humidity (RH) to 70∘ C/75%RH with testing after 2 and 4 weeks of storage. Each formulation contained two different fillers (47% w/w each), a disintegrant (5% w/w) and magnesium stearate (1% w/w). The results show that tablets stored at high humidity show increases in porosity and decreases in tensile strength, particularly if they contain a highly hygroscopic filler such as microcrystalline cellulose (MCC). For tablets stored at high temperature, the most commonly affected property was the tablet wettability, measured by sessile drop contact angle measurements. These results are considered in combination with the performance-controlling disintegration mechanism (Maclean et al., 2021) to identify the critical properties which influence the performance after storage.
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BACKGROUND: Early assessment of pH-dependent drug-drug-interactions (DDIs) for salts of poorly soluble weakly acidic compounds offers various advantages for patient safety, the pharmaceutical industry, and regulatory bodies. Biorelevant media and tests reflecting physiological changes during acid-reducing agent (ARA) co-administration can be used to explore and predict the extent of the pH effect during therapy with ARAs. METHODS: Solubility, one-stage and two-stage dissolution of tablets containing potassium raltegravir, the marketed salt form of this poorly soluble, weakly acidic drug, was investigated using biorelevant media specially designed to reflect administration without and during ARA co-therapy. The dissolution data were then converted into parameters suitable for input into an in silico model (Simcyp™) and the simulated plasma profiles were compared with available pharmacokinetic (PK) data from the literature. RESULTS: Dissolution of the potassium raltegravir formulation in media reflecting ARA co-administration, and thus elevated gastric pH, was faster and more complete than in experiments reflecting the low gastric pH observed in the absence of ARA co-administration. Simulations using data from dissolution experiments with ARA media appropriately bracketed the in vivo data for ARA co-administration in healthy volunteers. CONCLUSION: Dissolution data from in vitro experiments in biorelevant media reflecting physiological changes due to ARA co-administration provide valuable information about potassium raltegravir's behavior during concomitant ARA therapy. The approach may also be suitable for salts forms of other poorly soluble, weakly acidic drugs.
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Potasio , Sales (Química) , Simulación por Computador , Interacciones Farmacológicas , Humanos , Concentración de Iones de Hidrógeno , Modelos Biológicos , Raltegravir PotásicoRESUMEN
In 1920, Culex coronator was reported from San Benito, Texas, and later in Arizona, New Mexico, and Oklahoma. In 2005, this species was reported to be spreading across the southeastern USA. Now reported in 14 states, it has been found as far north as northern Oklahoma; Memphis, TN; and Suffolk, VA. The public health significance of Cx. coronator is not firmly established, even though it has been implicated as a potential vector of several arboviral diseases. This study aims to document additional Cx. coronator county-level records, to provide information about its continued expansion across the southern USA, and to provide a short research update into its vector potential. Data acquired through multistate collaborations and author collections resulted in 146 new county records from Alabama, Arkansas, Florida, Georgia, Louisiana, Mississippi, North Carolina, Oklahoma, South Carolina, and Texas. No new county records were presented for Arizona, New Mexico, Tennessee, or Virginia, which had previously reported this species. With these new data, this species has been documented in 386 counties in 14 states of the continental USA.
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Distribución Animal , Culex , Animales , Estados UnidosRESUMEN
The disintegration process of pharmaceutical tablets is a crucial step in the oral delivery of a drug. Tablet disintegration does not only refer to the break up of the interparticle bonds, but also relates to the liquid absorption and swelling behaviour of the tablet. This study demonstrates the use of the sessile drop method coupled with image processing and models to analyse the surface liquid absorption and swelling kinetics of four filler combinations (microcrystalline cellulose (MCC)/mannitol, MCC/lactose, MCC/dibasic calcium phosphate anhydrous (DCPA) and DCPA/lactose) with croscarmellose sodium as a disintegrant. Changes in the disintegration performance of these formulations were analysed by quantifying the effect of compression pressure and storage condition on characteristic liquid absorption and swelling parameters. The results indicate that the disintegration performance of the MCC/mannitol and MCC/lactose formulations are driven by the liquid absorption behaviour. For the MCC/DCPA formulation, both liquid absorption and swelling characteristics affect the disintegration time, whereas DCPA/lactose tablets is primarily controlled by swelling characteristics of the various excipients. The approach discussed in this study enables a rapid (<1 min) assessment of characteristic properties that are related to tablet disintegration to inform the design of the formulation, process settings and storage conditions.