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

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

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

Effect of Drug Loading Method on Drug Content and Drug Release from Calcium Pectinate Gel Beads

Drug-loaded calcium pectinate gel (CaPG) beads were prepared by either mixing, absorption, or swelling method. The effects of drug loading method as well as the drug loading factors (i.e., drug concentration, soaking time in drug solution, type of solvent) on drug content and drug release were investigated. The amount of drug uptake (i.e., drug content) into CaPG beads increased as the initial drug concentration increased and varied depending on the loading method. The in vitro release studies in 0.1 N hydrochloric acid (HCl) and pH 6.8 buffer indicated that the drug loading method affected drug release and release parameter, time for 50% of drug release (T50). The mixing method provided a faster drug release and lower T50 than the absorption method and swelling method, respectively. This is probably due to higher drug content in CaPG beads. The increased concentration of drug in soaking solution and soaking time resulted in higher drug content and thus faster drug release (lower in T50 values). When using 0.1 N HCl as solvent for soaking instead of water, the drug release was slower owing to the increase in molecular tortuosity of CaPG beads. The drug release was also affected by pH of the release medium in which drug release in 0.1 N HCl was faster than in pH 6.8 buffer