Flow and Tableting Behaviors of Some Egyptian Kaolin Powders as Potential Pharmaceutical Excipients

The present work aimed at assessing the pharmaceutical tableting properties of some Egyptian kaolin samples belong to the Abu Zenima kaolin deposits (estimated at 120 million tons). Four representative samples were selected based on kaolinite richness and their structural order-disorder degree, and after purification, they were dried at 70 ºC and heated from room temperature up to 400 ºC (10 ºC/min). Mineralogy, micromorphology, microtexture, granulometry, porosimetry, moisture content, bulk and tapped density, direct and indirect flowability, and tableting characteristics are studied. Results indicated that purified kaolin samples were made up of 95–99% kaolinite, <3% illite, 1% quartz and 1% anatase. The powder showed mesoporous character (pore diameters from 2 to 38 nm and total pore volume from 0.064 to 0.136 cm3/g) with dominance of fine nanosized particles (<1 um–10 nm). The powder flow characteristics of both the ordered (Hinckley Index HI > 0.7, crystallite size D001 > 30 nm) and disordered (HI < 0.7, D001 < 30 nm) kaolinite-rich samples have been improved (Hausner ratio between 1.24 and 1.09) as their densities were influenced by thermal treatment (with some observed changes in the kaolinite XRD reflection profiles) and by moisture content (variable between 2.98% and 5.82%). The obtained tablets exhibited hardness between 33 and 44 N only from the dehydrated powders at 400 ºC, with elastic recovery (ER) between 21.74% and 25.61%, ejection stress (ES) between 7.85 and 11.45 MPa and tensile fracture stress (TFS) between 1.85 and 2.32 MPa, which are strongly correlated with crystallinity (HI) and flowability (HR) parameters. These findings on quality indicators showed the promising pharmaceutical tabletability of the studied Egyptian kaolin powders and the optimization factors for their manufacturability and compactability.This work has been funded by the Egyptian Cultural Affairs and Missions Sector (Plan 2013–2014), Ministry of Higher Education, in collaboration with the Group CTS-946 (Junta de Andalucía) and MINECO project CGL2016-80833-R (Spain), and the grant funded by Erasmus+ KA1 mobility program 2016/2017

Selection of the suitable polymer for supercritical fluid assisted preparation of carvedilol solid dispersions

Solid dispersions production is one of the substantial approaches for improvement of poor drug solubility. Additionally, supercritical fluid assisted method for preparation of solid dispersions can offer many advantages in comparison to the conventional melting or solvent-evaporation methods. Miscibility analysis provides valuable guidance for selection of the most appropriate polymeric carrier for dispersion of the drug of interest. In addition to the increased drug release rate, solid dispersions should have proper mechanical attributes in order to be successfully formulated in the final solid dosage form such as tablet. Therefore, several pharmaceutical grade polymers have been selected for development of BCS Class II drug carvedilol (CARV) solid dispersions. They were compared based on behavior in supercritical CO 2 and affinity towards CARV calculated from the miscibility analysis. By utilization of the supercritical CO 2 assisted method, solid dispersions of CARV with the selected (co)polymers (polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), Soluplus® and Eudragit®) were obtained. Properties of the prepared CARV-polymer dispersions were observed by the polarizing and scanning electron microscopy and analyzed by differential scanning calorimetry and Fourier transform infrared spectroscopy. CARV was additionally characterized by X-ray powder diffraction. Furthermore, in vitro dissolution studies and dynamic compaction analysis were performed on the selected samples of solid dispersions. Among the studied polymers, PVP and HPMC have been identified as polymers with the highest affinity towards CARV, based on the calculated δ p values. This has been also confirmed with the highest dissolution efficiency of CARV-PVP and CARV-HPMC solid dispersions. Solid state characterization indicated that CARV was dispersed either molecularly, or in the amorphous form, depending on interactions with each polymer. Determination of CARV-PVP and CARV-HPMC mechanical properties revealed that CARV-PVP solid dispersion has superior compactibility and tabletability. Therefore, CARV-PVP solid dispersion has been highlighted as the most appropriate for the further development of tablets as the final dosage form. Presented study provides an example for efficient approach for development of poorly soluble drug solid dispersion with satisfactory tableting properties.This is the peer-reviewed version of the following article: Đuriš, J., Milovanović, S., Medarević, Đ., Dobričić, V., Dapčević, A.,& Ibrić, S.. (2019). Selection of the suitable polymer for supercritical fluid assisted preparation of carvedilol solid dispersions. International Journal of Pharmaceutics Elsevier Science Bv, Amsterdam., 554, 190-200. [https://doi.org/10.1016/j.ijpharm.2018.11.015]Published version [http://technorep.tmf.bg.ac.rs/handle/123456789/4335

Optimization and Prediction of Ibuprofen Release from 3D DLP Printlets Using Artificial Neural Networks

The aim of this work was to investigate effects of the formulation factors on tablet printability as well as to optimize and predict extended drug release from cross-linked polymeric ibuprofen printlets using an artificial neural network (ANN). Printlets were printed using digital light processing (DLP) technology from formulations containing polyethylene glycol diacrylate, polyethylene glycol, and water in concentrations according to D-optimal mixture design and 0.1% w/w riboflavin and 5% w/w ibuprofen. It was observed that with higher water content longer exposure time was required for successful printing. For understanding the effects of excipients and printing parameters on drug dissolution rate in DLP printlets two different neural networks were developed with using two commercially available softwares. After comparison of experimental and predicted values of in vitro dissolution at the corresponding time points for optimized formulation, the R2 experimental vs. predicted value was 0.9811 (neural network 1) and 0.9960 (neural network 2). According to difference f1 and similarity factor f2 (f1 = 14.30 and f2 = 52.15) neural network 1 with supervised multilayer perceptron, backpropagation algorithm, and linear activation function gave a similar dissolution profile to obtained experimental results, indicating that adequate ANN is able to set out an input&ndash;output relationship in DLP printing of pharmaceutics

Enhanced antimicrobial activity and physicochemical stability of rapid pyro-fabricated silver-kaolinite nanocomposite

The present research aims to enhance the antimicrobial activity of kaolinite surfaces by a one-step cost-effective and energy-efficient dry thermal reaction, producing an antibacterial and antifungal silver-kaolinite (Ag-Kao) nanocomposite agent. Pharmaceutical grade kaolin powder samples, with variable kaolinite structural order–disorder degree, were homogeneously mixed with silver nitrate in a proportion 1:4 AgNO:kaolin (w/w) and sintered at 400 °C for 30 min. The composition, microstructure, microtexture and surface characteristics of the pyro-fabricated nanocomposites were characterized by XRD/XRF diffractometry, differential scanning calorimetry DSC, FT-IR spectroscopy, TEM/EDX, zeta potential (mV) measured within the 2–12 pH range, and BET method. Physicochemical stability was evaluated by silver dissociation testing under close-neutral and acidic conditions with Ag content assay using ICP-OES. The resulting Ag-Kao nanocomposites exhibited bulk silver contents ranging from 9.29% to 13.32% with high physicochemical stability in both neutral and acidic mediums (Ag dissociation rate 1) produced platelet edge-clustered silver nanocrystals due to the abundance of the dangling hydroxyls on platelet edges, while the highly disordered kaolinite (HI < 1) provided homogeneous platelet basal-doped silver nanocrystals due to the presence of some residual charges by exposed basal hydroxyl groups with interplatelet silver diffusivity. At pH 2, the magnitude of the positive surface charge was influenced by the silver nanocrystal size. Nanocomposites with the smallest silver nanocrystals (10–5 nm) exhibited the highest positive zeta potential (+15.2 mV to +17.0 mV), while those with larger silver nanocrystals (up to 30 nm) indicated lower positive zeta potential values (+9.5 mV to +3.6 mV). Under the same testing conditions using the Mueller-Hinton broth microdilution method, the raw kaolin samples did not show any significant antimicrobial activity, while all the pyro-fabricated Ag-Kao nanocomposite samples showed potent antibacterial and antifungal activity at low doses (MIC range 0.1–0.0125 mg/mL). Therefore, modulation of the effective electrostatic surface charge of the kaolinite platelets, via thermal doping of silver within their basal planes and edges, was found to be strongly dependent on the pH as well as the size and microtexture of the silver nanocrystals (mainly controlled by the order–disorder degree HI). The resulting modified nanostructure, with physicochemical stability and the efficient surface properties of the designed pyro-fabricated nanocomposite, led to an enhanced synergistic biophysical antimicrobial activity.This research was supported by the Egyptian Cultural Affairs and Missions Sector (Plan number 7: 2012/2017), Ministry of Higher Education; Group CTS-946 (Junta de Andalucía, Spain); MINECO project (CGL2016-80833-R); Erasmus + KA1 mobility program 2016/2017; and the Ministry of Education, Science and Technological Development, Republic of Serbia. The first author is very grateful to Mrs. Nataša Stojković (Department of Microbiology), Mrs. Biljana Mihailović and Dr. Vladimir Dobričić (Department of Pharmaceutical Chemistry) of the Faculty of Pharmacy, University of Belgrade, Serbia for their technical assistance