Evaluation of the Disintegration Action of Soy Polysaccharide by Image Analysis.

Here we investigated the disintegration action of the natural superdisintegrant soy polysaccharide (SP) and benchmarked it against sodium starch glycolate (SSG) and crospovidone (XPVP). Kinetics and mechanism of disintegration of various tablet formulations were monitored using a USB microscope connected to a computer, followed by image analysis. SP acts mainly by a swelling mechanism and it is most effective at concentrations of 4-8%. Its disintegration action is comparable with that of SSG and XPVP, in most cases. However, SP underperforms compared with these superdisintegrants, in extremely hard tablets containing a hydrophobic component. Moreover, it is more negatively affected by the concentration of magnesium stearate than SSG and XPVP. The disintegration action of SP is not affected by pH and ionic strength of the medium, but it is compromised by the presence of ethanol. This indicates that the concomitant administration of alcoholic beverages might hamper the disintegration of SP-containing tablets. Overall, SP is a promising tablet disintegrant for pharmaceutical and nutraceutical products.

Influence of Testing Parameters on In Vitro Tramadol Release from Poloxamer Thermogels using the Immersion Cell Method.

The immersion cell is an in vitro performance test of drug release from semisolids. Several studies made use of immersion cells to investigate drug release from thermosensitive Poloxamer-based gels; however, specifications on the parameter setting are not yet available. Therefore, the aim of this study was to evaluate the influence of testing parameters on tramadol (a model drug) release, release rate, and dissolution efficiency (DE) from Poloxamer gels, using immersion cells. The thermosensitive gelling formulation showed batch-to-batch uniformity of gelling behavior, drug content, and drug release. The use of a membrane in the immersion cell resulted in slower drug release as compared to the absence of a membrane. Moreover, the faster the paddle rotation, the faster the drug release was. Membrane thickness showed a strong and significant linear relationship with corresponding DE values (Pearson's correlation coefficient, r = -0.9470; p = 0.004). Factors that did not influence drug release include paddle position, i.e., distance between paddle and membrane, as well as membrane mean pore size. This study sets forth the importance of carefully controlling the following parameters including presence/absence of membrane, paddle rotation speed, and membrane thickness during the setup of release experiments from gels using immersion cells.

Factors affecting the rheological behaviour of carbomer dispersions in hydroalcoholic medium: Towards the optimization of hand sanitiser gel formulations.

Hand sanitizers represent a primary measure for the prevention of transmissible infections, whose use has been greatly increased during CoViD-19 pandemic. Most of the commercially available products are hydrogels, employing carbomers as thickening agents. However, few information is still available regarding performances of carbomers in hydroalcoholic media containing a percentage of alcohols ≥ 60% v/v as recommended for disinfection. The aim of this study was to investigate the colloidal behaviour of carbomer 974 and carbomer 980 in hydroalcoholic media containing from 50 to 80% w/w of alcohol (ethanol or isopropanol) and neutralised with triethanolamine or aminomethyl propanol. Both carbomers provide transparent hydrogels in water, but carbomer 980 should be preferred for the formulation of hydrogel with a percentage of alcohol ≥ 50% w/w for its better solvation. The critical alcohol concentration (CAlC), above which polymer precipitation occurs, depends on the type of alcohol and base used. Carbomer dispersions with a higher content of alcohol can be prepared using aminomethyl propanol rather than triethanolamine. The choice of the more suitable components is fundamental for the isopropanol-based dispersions since the CAlC is closer to the recommended concentrations for disinfection. Overall, these results provide helpful insights for the correct preparation of alcohol-based hand sanitizers using carbomers.

Advancing the understanding of the tablet disintegration phenomenon - An update on recent studies.

Disintegration is the de-aggregation of particles within tablets upon exposure to aqueous fluids. Being an essential step in the bioavailability cascade, disintegration is a fundamental quality attribute of immediate release tablets. Although the disintegration phenomenon has been studied for over six decades, some gaps of knowledge and research questions still exist. Three reviews, published in 2015, 2016 and 2017, have discussed the literature relative to tablet disintegration and summarised the understanding of this topic. Yet, since then more studies have been published, adding to the established body of knowledge. This article guides a step forward towards the comprehension of disintegration by reviewing, concisely, the most recent scientific updates on this topic. Initially, we revisit the mechanisms of disintegration with relation to the three most used superdisintegrants, namely sodium starch glycolate, croscarmellose sodium and crospovidone. Then, the influence of formulation, storage, manufacturing and media conditions on disintegration is analysed. This is followed by an excursus on novel disintegrants. Finally, we highlight unanswered research questions and envision future research venues in the field.

Rheological properties of cellulosic thickeners in hydro-alcoholic media: The science behind the formulation of hand sanitizer gels.

Cellulosic-based thickeners are commonly used in the preparation of hydro-alcoholic hand sanitisers. Yet, little is known about the behaviour of these polymeric dispersions in hydro-alcoholic mixtures. Here, we studied the dispersion ability and rheology of hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose and sodium carboxymethyl cellulose in water-ethanol mixtures. Hydroxypropyl cellulose formed transparent dispersions across the entire range of ethanol concentrations, while a critical ethanol concentration (CEC), above which dispersions became turbid, was found for all the other polymers. At and below the CEC, all the rheological parameters followed a bell-like shape profile as a function of ethanol concentration. Moreover, the molecular weight and degree of substitution of the polymers influenced the rheological properties. The CEC and rheological behaviour of the dispersions were both dependent on the ethanol/polymer and water/polymer interactions. As hand disinfectants should contain 60-95% ethanol, polymers of higher CEC, such as hydroxypropyl cellulose and hydroxypropyl methylcellulose, are recommended.

Hot melt extruded zein for controlled delivery of diclofenac sodium: Effect of drug loading and medium composition.

This study evaluates the potential use of zein as an excipient in hot-melt extrusion for controlled delivery of diclofenac sodium (DS). Mixtures of zein, polyethylene glycol and drug were hot melt extruded and cut into 2 mm extrudates. Extrudates were characterised using differential scanning calorimetry, X-ray powder diffraction and scanning electron microscopy. The drug in the extrudates was found to be in the non-crystalline state, independent of the drug loading. Moreover, the drug release from extrudates was investigated. The release was directly dependent on the drug loading: a controlled and nearly zero-order release was obtained at the lowest drug loading (12.5% w/w), whereas almost immediate release was achieved at higher drug loadings, i.e. 25% and 37.5%. The release was inversely dependent on the ionic strength of the medium. The influence of digestive enzymes on drug release was also studied. Pancreatin, but not pepsin, was found to have a significant influence on the drug release as well as on the microstructure of zein extrudates. These data therefore support the potential use of zein as excipient in hot melt extrusion for controlled release purposes.

In vitro drug release from acetylated high amylose starch-zein films for oral colon-specific drug delivery.

This study describes the preparation of free films of zein with and without acetylated high amylose maize starch (HAS) and their corresponding coated tablets as a novel approach to colonic drug delivery. We hypothesise that the embedding of a digestible starch component within the inert zein would allow the film to remain intact until the large intestine is reached. Free films of zein alone and starch/zein were prepared and characterized. SEM and AFM images of film surface showed that films were morphologically inhomogeneous, particularly at lower HAS/Zein ratios; however, nanothermal analysis data suggested that these differences in appearance within the same film are not compositional differences. Moreover, FT-IR could detect no molecular interaction between the two polymers. Paracetamol tablets were coated with HAS/Zein aqueous based coatings of different compositions to a TWG of 20%. Drug release from zein alone and 1:5 HAS/Zein coated tablets under upper gastrointestinal conditions (pH 1.2, pH 6.8 with pepsin and pancreatin included) was very similar (for example approximately 12% and 14% of the drug was released, respectively, after 6 h in a sequential in vitro test), suggesting that release in this region is limited and is not influenced by the presence of HAS in the ratio to zein under study. Studies using an in vitro colon model showed that under simulated colonic conditions, the drug release was significantly (p < 0.05) more rapid from 1:5 HAS/Zein, compared to the zein alone coating formulation. These data therefore support the potential use of zein-starch mixed films for colonic targeting purposes.

The influence of ethanol on superdisintegrants and on tablets disintegration.

Disintegration of immediate release tablets originates from the volume expansion of disintegrants within the formulation. Here, we study the impact of ethanol on the disintegrant expansion and on tablets disintegration. The three most commonly used superdisintegrants, namely sodium starch glycolate (SSG), crospovidone (PVPP) and croscarmellose sodium (CCS) were investigated alone and incorporated in dicalcium phosphate and in drug-containing tablets. High (i.e. 40%), but not moderate (i.e. 10%), aqueous ethanol concentrations reduce the size expansion of the three disintegrants compared to water. This "ethanol effect" is the greatest for SSG, followed by CCS and then PVPP. Moreover, the presence of ethanol in the media can significantly influence the disintegration time of drug-containing tablets via affecting both the disintegrant action itself and the drug solubility. For example, the disintegration time of theophylline tablets containing SSG is 8.1-fold greater in 40% aqueous ethanol compared to water. Overall, this study brought to light the existence of a potentially significant interference of alcohol with the disintegration phenomenon, suggesting that the concomitant administration of tablets and intake of alcoholic beverages may affect, in some cases, tablets disintegration. More studies are now needed to verify the importance of the "ethanol effect" on disintegration of commercial dosage forms. Our findings also suggest that PVPP is the disintegrant that is the least affected by alcohol.

A Simple and Inexpensive Image Analysis Technique to Study the Effect of Disintegrants Concentration and Diluents Type on Disintegration.

Tablets disintegration is often the result of a size expansion of the tablets. In this study, we quantified the extent and direction of size expansion of tablets during disintegration, using readily available techniques, that is, a digital camera and public domain image analysis software. After validating the method, the influence of disintegrants concentration and diluents type on kinetics and mechanisms of disintegration were studied. Tablets containing diluent, disintegrant (sodium starch glycolate, crospovidone, or croscarmellose sodium), and lubricant were prepared by direct compression. Projected area and aspect ratio of the tablets were monitored using image analysis techniques. The developed method could describe the kinetics and mechanisms of disintegration qualitatively and quantitatively. Sodium starch glycolate and crospovidone acted purely by swelling and shape recovery mechanisms. Instead, croscarmellose sodium worked by a combination of both mechanisms, the extent of which changed depending on its concentration and the diluent type. We anticipate that the method described here could provide a framework for the routine screening of tablets disintegration using readily available equipment.