Tablet Disintegration and Dispersion under In Vivo-like Hydrodynamic Conditions

Disintegration and dispersion are functional properties of tablets relevant for the desired API release. The standard disintegration test (SDT) described in different pharmacopoeias provides only limited information on these complex processes. It is considered not to be comparable to the biorelevant conditions due to the frequent occurrence of high hydrodynamic forces, among other reasons. In this study, 3D tomographic laser-induced fluorescence imaging (3D Tomo-LIF) is applied to analyse tablet disintegration and dispersion. Disintegration time (DT) and time-resolved particle size distribution in close proximity to the tablet are determined in a continuously operated flow channel, adjustable to very low fluid velocities. A case study on tablets of different porosity, which are composed of pharmaceutical polymers labelled with a fluorescent dye, a filler, and disintegrants, is presented to demonstrate the functionality and precision of the novel method. DT results from 3D Tomo-LIF are compared with results from the SDT, confirming the analytical limitations of the pharmacopoeial disintegration test. Results from the 3D Tomo-LIF method proved a strong impact of fluid velocity on disintegration and dispersion. Generally, shorter DTs were determined when cross-linked sodium carboxymethly cellulose (NaCMCXL) was used as disintegrant compared to polyvinyl polypyrrolidone (PVPP). Tablets containing Kollidon VA64 were found to disintegrate by surface erosion. The novel method provides an in-depth understanding of the functional behaviour of the tablet material, composition and structural properties under in vivo-like hydrodynamic forces regarding disintegration and the temporal progress of dispersion. We consider the 3D Tomo-LIF in vitro method to be of improved biorelevance in terms of hydrodynamic conditions in the human stomach.

Rapid tablet swelling and disintegration during exposure to brightness-mode ultrasound

Controlled tablet disintegration is useful for chemical consistency checks. This study monitored the swelling of 54 analgesia tablets from two different batches, during 13–6-MHz brightness-mode sonication and simultaneous video recording. The tablets were placed on an acoustic reflector inside a container and sonicated from the top. Sonication shortened the displacement half-life by 17%–27%. During tablet swelling, their speed of sound increased linearly, confirming the linearity of the this process. Diagnostic ultrasound significantly decreased tablet disintegration times, supporting the ultrasound–microbubble interaction hypothesis.

Swallowing Gel for Patients with Dysphagia: A Novel Application of Chitosan

Dysphagia refers to difficulty swallowing certain foods, liquids, or pills. It is common among the elderly with chronic diseases who need to take drugs for long periods. Therefore, dysphagia might reduce compliance with oral drug administration in the aging population. Many pharmaceutical companies search for new products to serve as swallowing aids. Existing products are expensive and do not suit all geriatric patients. Therefore, this study aimed to develop and investigate pill swallowing aid gels prepared from carboxymethyl cellulose and chitosan. We formulated gels by dissolving different concentrations of carboxymethyl cellulose and low or high molecular weight chitosan in solvents to find appropriate gel rheology properties. We then added several portions of glycerin as the glidant of the formulation. We found that the optimized gel formulation was 6.25% (w/w) chitosan with a molecular weight of 80–120 kDa dissolved in 1.2% acetic acid and 4% (w/w) glycerin. The developed pill swallowing gel’s rheology was pseudoplastic with a viscosity of 73.74 ± 3.20 Pa⸱s. The developed chitosan gel had enhanced flow ability; it allowed the pill to cross a 300 mm tube within 6 s, while the reference product took 3 s. Even though the reference product could carry the pill in the tube faster, the chitosan gel better covered the pill, making it more convenient to use. Finally, using a theophylline tablet as a model tablet dosage form, we assessed the gel’s effect on drug disintegration and dissolution. The chitosan gel delayed the tablet disintegration time by about 3–7 min and slightly affected the theophylline dissolution rate. Lastly, all gels were physically stable after a month of storage in the stress condition. These results show the feasibility of manufacturing a chitosan gel usable as a pill swallowing gel for patients with dysphagia.

Digital Image Disintegration Analysis: a Novel Quality Control Method for Fast Disintegrating Tablets

Measuring tablet disintegration is essential for quality control purposes; however, no established method adequately accounts for the timeframe or small volumes of the medium associated with the dissipation process for fast disintegrating tablets (FDTs) in the mouth. We hypothesised that digital imaging to measure disintegration in a low volume of the medium might discriminate between different types of FTD formulation. A digital image disintegration analysis (DIDA) was designed to measure tablet disintegration in 0.05–0.7 mL of medium. A temperature-controlled black vessel was 3D-printed to match the dimensions of each tablet under investigation. An overhead camera recorded the mean grey value of the tablet as a measure of the percentage of the formulation which remained intact as a function of time. Imodium Instants, Nurofen Meltlets and a developmental freeze-dried pilocarpine formulation were investigated. The imaging approach proved effective in discriminating the disintegration of different tablets (p < 0.05). For example, 10 s after 0.7 mL of a saliva simulant was applied, 2.0 ± 0.3% of the new pilocarpine tablet remained, whereas at the same time point, 22 ± 9% of the Imodium Instants had not undergone disintegration (temperature within the vessel was 37 ± 0.5°C). Nurofen Meltlets were observed to swell and showed a percentage recovery of 120.7 ± 2.4% and 135.0 ± 6.1% when 0.05 mL and 0.7 mL volumes were used, respectively. Thus, the new digital image disintegration analysis, DIDA, reported here effectively evaluated fast disintegrating tablets and has the potential as a quality control method for such formulations.

Effect of Yogurt as a Deglutition Aid on the Disintegration and Dissolution of Oral Tablets

With an aging society, the number of people with dysphagia has increased. Patients with dysphagia not only find it difficult to eat and drink, but also to take oral medications. Swallowing aid foods, such as deglutition aid jellies and food thickeners are often used to help patients take oral medications. However, the inappropriate use of swallowing aids can decrease the pharmacological activity of the medications. Yogurt is nutritious and easy for patients with dysphagia to eat. Although yogurt is sometimes used to help take medications, its influence on them is poorly understood. In this study, we compared the physical properties and the effects of yogurt on disintegration and dissolution profiles of various oral tablets with those of deglutition aid jelly and xanthan gum-based food thickener. Yogurt and food thickener were found to extend the disintegration time of several tablets, but it remained within a few minutes. Although dissolution of magnesium oxide tablets decreased by 6%, 14%, and 25% after immersion in deglutition aid jelly, food thickener, and yogurt, respectively at 15 min, this decrease reduced with time. Rheological measurements showed that yogurt and food thickeners exhibited a weak gel structure and therefore had better fluidity than deglutition aid jelly. The viscosity and adhesiveness of yogurt were higher than those of food thickener, which delayed tablet disintegration and reduced the dissolution rate. However, these effects were not large. Yogurt may be a useful swallowing aid for patients with dysphagia taking oral medications.

Evaluation of Novel co-processed excipient for fast disintegration of aspirin tablet formulations

Co-processing is a technique that ensures sub-particulate interaction of individual excipients leading to overall functionality of the resulting excipient. The aim of this study is to co-process Cyperus esculentus starch with mannitol by fusion and evaluate its effect on tablet disintegration and in vitro dissolution. Co-processed excipients were prepared from Cyperus esculentus starch and mannitol by fusion in ratios of 1:1, 1:2 and 2:1 (CM1, CM2, and CM3 respectively) and evaluated for flow and swelling properties. The excipients were incorporated into Aspirin tablet formulations at 5 %w/w by direct compression (FM1, FM2, FM3 respectively). Similar tablets were prepared using sodium starch glycolate (FSG) and the formulations were assessed for hardness, friability, wetting time, disintegrationtime and in vitro dissolution profile. All the prepared excipients possessed excellent flow with Carr’s index between 17.31 and 20.78 and Hausner ratio between 1.21 and 1.26. CM3 had the highest swelling profile (1.491) while CM2 had the lowest (1.321). Formulation FM1 had the highest tensile strength (14.12 N/cm2 ) but slower wetting time (34.33 sec) compared to FM3 with tensile strength of 11.32 N/cm2 and wetting time of 9.00 sec. Disintegration time of CM3 (4.26 min) was comparable to that of FSG (4.01 min); their dissolution profile was also found to be similar. Coprocessing Cyperus esculentus starch and mannitol by fusion (2:1) influenced tablet disintegration and in vitro dissolution and has potential to be used in manufacture of fast dissolving tablet formulations. Keywords: Co-processing; Cyperus esculentus starch; Mannitol; Disintegration; Dissolution