Oblikovanje i vrednovanje plutajućih uljnih mikrozrnaca loratadina s produljenim zadržavanjem u želucu

Gastro retentive controlled release system of loratadine was formulated to increase the residence time in stomach and to modulate the release behaviour of the drug. Oil entrapped floating microbeads prepared by emulsion gelation method were optimized by 23 factorial design and a polymer ratio of 2.5:1.5 (pectin: sodium alginate) by mass, 15% (m/v) of oil (mineral oil or castor oil) and 0.45 mol L-1 calcium chloride solution were selected as the optimized processing conditions for the desired buoyancy and physical stability. In vitro drug release in fed state conditions demonstrated sustained release of loratadine for 8 h that best fitted the Peppas model with n < 0.45. The ethylcellulose coating on microbeads optimized by 22 factorial design resulted in controlled release formulation of loratadine that provided zero-order release for 8 h.U radu je opisana priprava plutajućih mikrozrnaca za kontrolirano oslobađanje loratadina metodom želiranja emulzije. Mikrozrnca sadrže ulja, a njihovo zadržavanje u želucu je produljeno. Priprava mikrozrnaca je optimirana 23 faktorijalnim dizajnom. Pripravci optimalne sposobnosti plutanja i stabilnosti dobiveni su uz omjer masa pektina i natrijevog alginata 2,5:1,5, udio mineralnog ulja ili ulja kastora 15% (m/v) i koncentraciju kalcijevog klorida 0,45 mol L1. Iz tih se mikrozrnaca loratadin oslobađa in vitro tijekom 8 h, a oslobađanje slijedi Peppasov model ako je n < 0,45. Mikrozrnca presvučena etilcelulozom optimirana 22 faktorijalnim dizajnom slijede kinetiku nultog reda tijekom 8 h

Biological evaluation of alginate-based hydrogels, with antimicrobial features by Ce(III) incorporation, as vehicles for a bone substitute

In this work three different hydrogels were developed to associate, as vehicles, with the synthetic bone substitute GR-HA. One based on an alginate matrix (Alg); a second on a mixture of alginate and chitosan (Alg/Ch); and a third on alginate and hyaluronate (Alg/HA), using Ca2+ ions as cross-linking agents. The hydrogels, as well as the respective injectable bone substitutes (IBSs), were fully characterized from the physical-chemical point of view. Weight change studies proved that all hydrogels were able to swell and degrade within 72 hours at pH 7.4 and 4.0, being Alg/HA the hydrogel with the highest degradation rate (80%). Rheology studies demonstrated that all hydrogels are non-Newtonian viscoelastic fluids, and injectability tests showed that IBSs presented low maximum extrusion forces, as well as quite stable average forces. In conclusion, the studied hydrogels present the necessary features to be successfully used as vehicles of GR-HA, particularly the hydrogel Alg/HA.The authors would like to acknowledge the financial support from FCT (Fundacao para a Ciencia e a Tecnologia) through the grant SFRH/BD/76237/2011 and project ENMED/0002/2010, from FEDER funds through the program COMPETE-Programa Operacional Factores de Competitividade-under the project PEst-C/EME/UI0285/2011, as well as to the project I&DT BIOMAT&CELL n. 1372

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated

Optimization of Lipid-Based Nanoparticles Formulation Loaded with Biological Product Using A Novel Design Vortex Tube Reactor via Flow Chemistry

Kittipat Suwanpitak,1 Kampanart Huanbutta,2 Nopphon Weeranoppanant,3 Pornsak Sriamornsak,4,5 Chonlada Panpipat,1 Tanikan Sangnim1 1Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, 20131, Thailand; 2Department of Manufacturing Pharmacy, College of Pharmacy, Rangsit University, Pathum Thani, 12000, Thailand; 3Department of Chemical Engineering, Faculty of Engineering, Burapha University, Chonburi, 20131, Thailand; 4Department of Industrial Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand; 5Academy of Science, the Royal Society of Thailand, Bangkok, 10300, ThailandCorrespondence: Tanikan Sangnim, Faculty of Pharmaceutical Sciences, Burapha University, 169, Seansook, Muang, Chonburi, 20131, Thailand, Email [email protected]: Lipid-based nanoparticles (LNPs) is increasingly recognized for their potential in drug delivery, offering protection to hydrophobic drugs from degradation. Industrial synthesis of LNPs, exemplified by Pfizer-BioNTech and Moderna mRNA vaccines, utilizes flow chemistry or microfluidics, showcasing its scalability. This study explores the utilization of a novel design reactor, the vortex tube reactor, within flow chemistry for LNPs synthesis, aiming to optimize its conditions and compare them with batch synthesis.Methods: LNPs were synthesized using the vortex tube reactor, incorporating bovine serum albumin (BSA) as a model drug in the aqueous phase, alongside 1.2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol in the organic phase. Design of experiments (DoE), specifically Box-Behnken design, was employed to optimize parameters, including X1: the flow rate ratio (10– 100 mL/min), X2: the aqueous-to-organic volumetric ratio (1:1– 10:1), and X3: the number of reactor units (1– 5 units). Responses evaluated encompassed physical properties and productivity. Optimized conditions were determined by minimizing particle size (Y1), polydispersity index (Y2), and zeta potential (Y3), while maximizing entrapment efficiency (Y4), drug loading (Y5), and productivity (Y5).Results: Results indicated that optimal conditions were achieved at X1 of 100 mL/min, X2 of 5.278, and X3 of 1 unit. LNPs synthesized under these conditions exhibited favorable physical properties and productivity, with uniformity maintained across batches. The vortex tube reactor demonstrated superiority over batch synthesis, yielding smaller particles (166.23 ± 0.98 nm), more uniform nanoparticles (PDI 0.17 ± 0.01), and higher entrapment (67.75 ± 1.55%) and loading capacities (36.39 ± 0.83%), indicative of enhanced productivity (313.4 ± 12.88 mg/min).Conclusion: This study elucidates the potential of flow chemistry, particularly utilizing the vortex tube reactor, for large-scale LNPs formulation, offering insights into parameter relationships and advancing nanoparticle synthesis for drug delivery applications. Keywords: flow chemistry, lipid-based nanoparticles, nanoparticles synthesis, biological produc

Direct Compression Behavior of Low- and High-Methoxylated Pectins

The objective of this study was to evaluate possible usefulness of pectins for direct compression of tablets. The deformation behavior of pectin grades of different degree of methoxylation (DM), namely, 5%, 10%, 25%, 35%, 40%, 50%, and 60% were, examined in terms of yield pressures (YP) derived from Heckel profiles for both compression and decompression and measurements of elastic recovery after ejection. All pectin grades showed a high degree of elastic recovery. DM 60% exhibited most plastic deformation (YP 70.4 MPa) whereas DM 5% (104.6 MPa) and DM 10% (114.7 MPa) least. However, DM 60% gave no coherent tablets, whereas tablet tensile strengths for DM 5% and DM 10% were comparable to Starch 1500®. Also, Heckel profiles were similar to Starch 1500®. For sieved fractions (180–250 and 90–125 μm) of DM 25% and DM 40% originating from the very same batch, YPs were alike, indicating minor effects of particle size. These facts indicate that DM is important for the compaction behavior, and batch-to-batch variability should also be considered. Therefore, pectins of low degree of methoxylation may have a potential as direct compression excipients

Enteric coated HPMC capsules plugged with 5-FU loaded microsponges: a potential approach for treatment of colon cancer

The work was aimed at developing novel enteric coated HPMC capsules (ECHC) plugged with 5 Florouracil (5-FU) loaded Microsponges in combination with calcium pectinate beads. Modified quasi-emulsion solvent diffusion method was used to formulate microsponges based on 32 factorial design and the effects of independent variables (volume of organic solvent and Eudragit RS100 content) on the dependent variables (Particle size, %EE & % CDR) were determined. The optimized microsponges (F4) were characterized by SEM, PXRD, TGA and were plugged along with calcium pectinate beads in HPMC capsules and the HPMC capsules were further coated with enteric polymer Eudragit L 100 (Ed-L100) and/ or Eudrgit S 100 (Ed-S 100) in different proportions. In vitro release study of ECHC was performed in various release media sequentially SGF for 2 h, followed by SIF for the next 6 h and then in SCF (in the presence and absence of pectinase enzyme for further 16 h). Drug release was retarded on coating with EdS-100 in comparison to blend of EdS-100: EdL-100 coating. The percentage of 5-FU released at the end of 24 h from ECHC 3 was 97.83 ± 0.12% in the presence of pectinase whereas in control study it was 40.08 ± 0.02% drug. The optimized formulation was subjected to in vivo Roentgenographic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon targeted capsules. Pharmacokinetic studies in New Zealand white rabbits were conducted to determine the extent of systemic exposure provided by the developed formulation in comparison to 5-FU aqueous solutions. Thus, enteric coated HPMC capsules plugged with 5-FU loaded microsponges and calcium pectinate beads proved to be promising dosage form for colon targeted drug delivery to treat colorectal cancer

Preparation and characterization of alginate and gelatin microcapsules containing Lactobacillus rhamnosus

ABSTRACT This paper describes the preparation and characterization of alginate beads coated with gelatin and containing Lactobacillus rhamnosus. Capsules were obtained by extrusion method using CaCl2 as cross linker. An experimental design was performed using alginate and gelatin concentrations as the variables investigated, while the response variable was the concentration of viable cells. Beads were characterized in terms of size, morphology, scanning electron microscopy (SEM), moisture content, Fourier Transform Infrared Spectrometry (FTIR), thermal behavior and cell viability during storage. The results showed that the highest concentration of viable cells (4.2 x 109 CFU/g) was obtained for 1 % w/v of alginate and 0.1 % w/v of gelatin. Capsules were predominantly spherical with a rough surface, a narrow size distribution ranging from 1.53 to 1.90 mm and a moisture content of 97.70 ± 0.03 %. Furthermore, FTIR and thermogravimetric analysis indicated an interaction between alginate-gelatin. Cell concentration of alginate/gelatin microcapsules was 105 CFU/g after 4 months of storage at 8 oC