The influence of fillers on theophylline release from clay matrices

Abstract: The objectives of this study were to investigate the suitability of magnesium aluminium silicate (MAS) (Veegum®) to control drug release of a model drug, theophylline, from tablet matrices. To this end, the performance of three commonly used fillers namely: lactose, microcrystalline cellulose (Avicel PH102; MCC), and pre-gelatinized starch, Starch 1500 PGS), were evaluated against Veegum®. The physico-mechanical properties of the tablet matrices were studied along with dissolution studies to determine the effect of single or binary mixtures of the excipients on the drug release pattern. A DSC hydration methodology was also employed to characterize the states of water present in the tablet matrices and to determine any impact on drug release. Formulations containing MAS alone produced compacts with the lowest hardness (4.5 kp) whereas formulations containing MCC alone produced the hardest tablets (17.2 kp). Dissolution studies suggested that matrices containing MAS alone released the theophylline quickest as compared to lactose, MCC or PGS. It was difficult to establish a trend of the bound and free water states in the tablet matrices; however the formulation containing only MAS had the highest bound water at 29 %. The results therefore show that theophylline does not interact with MAS. As such the dominant factor in controlling drug release using MAS requires interaction or intercalation with a cationic drug. In the absence of this however, other excipients can play a role in controlling drug release. Keywords: Veegum, clay matrices, DSC hydration, Magnesium aluminium silicate, filler

Conservation Agriculture as Practised in Ghana

This case study presents the status of conservation agriculture in Ghana. It is one in a series of eight case studies about conservation agriculture in Africa, which were developed within the framework of a collaboration between CIRAD (French Agricultural Research Centre for International Development), FAO (Food and Agriculture Organization of the United Nations), RELMA-in-ICRAF (Regional Land Management Unit of the World Agroforestry Centre) and ACT (African Conservation Tillage Network)

The dissolution and solid-state behaviours of coground ibuprofen–glucosamine HCl

The cogrinding technique is one of most effective methods for improving the dissolution of poorly water-soluble drugs and it is superior to other approaches from an economical as well as an environmental standpoint, as the technique does not require any toxic organic solvents. Present work explores the role of d-glucosamine HCl (GL) as a potential excipient to improve dissolution of a low melting point drug, ibuprofen (Ibu), using physical mixtures and coground formulations. The dissolution of the poorly soluble drug has been improved by changing the ratio of Ibu:GL and also grinding time. The results also showed that although GL can enhance the solubility of Ibu, it also reduces pH around the Ibu particles which led to poor dissolution performance when the concentration of GL is high. The effect of GL on the solubility of Ibu could be misleading if the pH of the final solution was not measured. Grinding reduced the particle size of GL significantly but in case of Ibu it was less effective. Solid state analysis (XRPD, DSC, and FT-IR) showed that ibuprofen is stable under grinding conditions, but the presence of high concentration of GL in samples subjected to high grinding times caused changes in FT-IR spectrum of Ibu which could be due to intermolecular hydrogen bond or esterification between the carboxylic acid group in the ibuprofen and hydroxyl group in the GL

Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions

This work explores the use of both spray drying and D-glucosamine HCl (GLU) as a hydrophilic carrier to improve the dissolution rate of piroxicam (PXM) whilst investigating the electrostatic charges associated with the spray drying process. Spray dried PXM:GLU solid dispersions were prepared and characterised (XRPD, DSC, SEM). Dissolution and triboelectric charging was also conducted. The results showed that the spray dried PXM alone, without GLU produced some PXM form II (DSC results) with no enhancement in solubility relative to that of the parent PXM. XRPD results also showed the spray drying process to decrease the crystallinity of GLU and solid dispersions produced. The presence of GLU improved the dissolution rate of PXM. Spray dried PXM: GLU at a ratio of 2:1 had the most improved dissolution. The spray drying process generally yielded PXM-GLU spherical particles of around 2.5 µm which may have contributed to the improved dissolution. PXM showed a higher tendency for charging in comparison to the carrier GLU (- 3.8 versus 0.5 nC/g for untreated material and -7.5 versus 3.1 nC/g for spray dried materials). Spray dried PXM and spray dried GLU demonstrated higher charge densities than untreated PXM and untreated GLU, respectively. Regardless of PXM:GLU ratio, all spray dried PXM:GLU solid dispersions showed a negligible charge density (net-CMR: 0.1 – 0.3 3nC/g). Spray drying of PXM:GLU solid dispersions can be used to produce formulation powders with practically no charge and thereby improving handling as well as dissolution behaviour of PXM

Image Segmentation with Human-in-the-loop in Automated De-caking Process for Powder Bed Additive Manufacturing

Additive manufacturing (AM) becomes a critical technology that increases the speed and flexibility of production and reduces the lead time for high-mix, low-volume manufacturing. One of the major bottlenecks in further increasing its productivity lies around its post-processing procedures. This work focuses on tackling a critical and inevitable step in powder-bed additive manufacturing processes, i.e., powder cleaning or de-caking. Pressing concerns can be raised with human involvement when performing this task manually. Therefore, a robot-driven automatic powder cleaning system could be an alternative to reducing time consumption and increasing safety for AM operators. However, since the color and surface texture of the powder residuals and the sintered parts are similar from a computer vision perspective, it can be challenging for robots to plan their cleaning path. This study proposes a machine learning framework incorporating image segmentation and eye tracking to de-cake the parts printed by a powder bed additive manufacturing process. The proposed framework intends to partially incorporate human biological behaviors to increase the performance of an image segmentation algorithm to assist the path planning for the robot de-caking system. The proposed framework is verified and evaluated by comparing it with the state-of-the-art image segmentation algorithms. Case studies were utilized to validate and verify the proposed human-in-the-loop algorithms. With a mean accuracy, f1-score, precision, and IoU score of 81.2%, 82.3%, 85.8%, and 66.9%, respectively, the suggested HITL eye tracking plus segmentation framework produced the best performance out of all the algorithms evaluated and compared. Regarding computational time, the suggested HITL framework matches the running times of the other test existing models, with a mean time of 0.510655 seconds and a standard deviation of 0.008387. Finally, future works and directions are presented and discussed. A significant portion of this work can be found in (Asare-Manu et al., 2023

Using small-angle X-ray scattering to investigate the compaction behaviour of a granulated clay

The compaction behaviour of a commercial granulated clay (magnesium aluminium smectite, gMgSm) was investigated using macroscopic pressure-density measurements, X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray microtomography (XμT) and small-angle X-ray scattering (SAXS). This material was studied as a potential compaction excipient for pharmaceutical tabletting, but also as a model system demonstrating the capabilities of SAXS for investigating compaction in other situations. Bulk compaction measurements showed that the gMgSm was more difficult to compact than polymeric pharmaceutical excipients such as spheronised microcrystalline cellulose (sMCC), corresponding to harder granules. Moreover, in spite of using lubrication (magnesium stearate) on the tooling surfaces, rather high ejection forces were observed, which may cause problems during commercial tabletting, requiring further amelioration. Although the compacted gMgSm specimens were more porous, however, they still exhibited acceptable cohesive strengths, comparable to sMCC. Hence, there may be scope for using granular clay as one component of a tabletting formulation. Following principles established in previous work, SAXS revealed information concerning the intragranular structure of the gMgSm and its response to compaction. The results showed that little compression of the intragranular morphology occurred below a relative density of 0 · 6, suggesting that granule rearrangements or fragmentation were the dominant mechanisms during this stage. By contrast, granule deformation became considerably more important at higher relative density, which also coincided with a significant increase in the cohesive strength of compacted specimens. Spatially-resolved SAXS data was also used to investigate local variations in compaction behaviour within specimens of different shape. The results revealed the expected patterns of density variations within flat-faced cylindrical specimens. Significant variations in density, the magnitude of compressive strain and principal strain direction were also revealed in the vicinity of a debossed feature (a diametral notch) and within bi-convex specimens. The variations in compaction around the debossed notch, with a small region of high density below and low density along the flanks, appeared to be responsible for extensive cracking, which could also cause problems in commercial tabletting

Variable-focus microscopy and UV surface dissolution imaging as complementary techniques in intrinsic dissolution rate determination

This work reports a novel approach to the assessment of the surface properties of compacts used in Surface Dissolution Imaging (SDI). SDI is useful for determining intrinsic dissolution rate (IDR), an important parameter in early stage drug development. Surface topography, post-compaction and post-SDI run, have been measured using a non-contact, optical, three-dimensional microscope based on focus variation, the Alicona Infinite Focus Microscope, with the aim of correlating the IDRs to the surface properties. Ibuprofen (IBU) was used as a model poorly-soluble drug. DSC and XRD were used to monitor possible polymorphic changes that may have occurred post-compaction and post-SDI run. IBUs IDR decreased from 0.033 mg/min/cm2 to 0.022 mg/min/cm2 from 10 to 20 min, respectively, during the experiment. XRD and DSC showed no form changes during the SDI run. The surface topography images showed that a distinct imprint was embossed on the surfaces of some compacts which could affect IDRs. Surface parameter values were associated with the SDI experiments which showed strong correlations with the IDR values. The variable-focus microscope can be used as a complimentary tool in the determination of IDR values from the SDI

The influence of hydroalcoholic media on the performance of Grewia polysaccharide in sustained release tablets

Co-administration of drugs with alcohol can affect the plasma concentration of drugs in patients. It is also known that the excipients used in the formulation of drugs may not always be resistant to alcohol. This study evaluates effect of varying alcohol concentrations on theophylline release from two grades of Grewia mollis polysaccharides. X-ray microtomography showed that native polysaccharide formulation compacts were not homogenous after the mixing process resulting in its failure in swelling studies. Removal of starch from the native polysaccharide resulted in homogenous formulation compacts resistant to damage in high alcoholic media in pH 6.8 (40%v/v absolute ethanol). Destarched polymer compacts had a significantly higher hardness (375 N) than that of the native polysaccharide (82 N) and HPMC K4 M (146 N). Dissolution studies showed similarity at all levels of alcohol tested (f2 = 57-91) in simulated gastric media (pH 1.2). The dissolution profiles in the simulated intestinal fluids were also similar (f2 = 60-94), with the exception of the native polysaccharide in pH 6.8 (40%v/v absolute ethanol) (f2 = 43). This work highlights the properties of Grewia polysaccharide as a matrix former that can resist high alcoholic effects therefore; it may be suitable as an alternative to some of the commercially available matrix formers with wider applications for drug delivery as a cheaper alternative in the developing world

Spironolactone loaded nanostructured lipid carrier gel for effective treatment of mild and moderate acne vulgaris: a randomized, double-blind, prospective trial

Spironolactone (SP) known as an anti-androgen drug, has been proven to be effective in treatment of acne. The quest to minimize the unnecessary systemic side effects associated with the oral drug administration of spironolactone, has led to a growing interest of loading SP on lipid nanoparticles to deliver the drug in a topical formulation. The aim of the current investigation was to prepare and compare the performance of SP loaded nanostructured lipid carrier (SP-NLC) and SP alcoholic gels (SP-ALC) on two groups of respective patient populations, group A and group B in the treatment of mild to moderate acne vulgaris. The results showed that SPNLCs were spherical in shape with an average diameter of ~240 nm. The polydispersity index (PI) and zeta potential of these nanoparticles were 0.286 and -21.4 respectively. The gels showed non-Newtonian independent pseudoplastic and shear thinning behavior. The SP-NLCs was not toxic to fibroblast cell strains at the 24 and 48 h periods. Results showed that the mean number of total lesions (37.66 ± 9.27) and non-inflammatory lesions (29.26 ± 7.99) in group A significantly decreased to 20.31 ± 6.58 (p<0.05) and to 13.95 ± 5.22 (p<0.05) respectively. A similar pattern was observed for group B where the mean number of total lesions and non-inflammatory lesions reduced from 33.73 ± 9.40 to 19.13 ± 5.53 (p<0.05) and from 25.65±8.12 to 13.45 ± 4.48 (p<0.05) respectively. The total lesion count (TLC) was significantly decreased from 37.16 ± 9.28 to 19.63 ± 6.36 (for group A; p<0.071) and 32.60 ± 9.32 to 18.33 ± 5.55 (for group B; p<0.05) respectively. After treatment with SP-NLC for 8 weeks, the water content of the skin significantly (p<0.05) increased from 37.44 ± 8.85 to 45.69 ± 19.34 instrumental units. Therefore, the SP-NLC gel may help in controlling acne vulgaris with skin care benefits