Matrix Erosion Research Articles

Release mechanisms of bovine serum albumin loaded-PLGA microspheres prepared by ultra-fine particle processing system.

The ultra-fine particle processing system (UPPS) previously developed by our lab has been used to prepare various microparticulate formulations. Microspheres prepared by UPPS can achieve sustained release with a reduced initial burst compared to the microspheres prepared by the conventional water-in-oil-in-water (W/O/W) double emulsion technique. However, the in vitro drug release mechanism of the microspheres prepared by UPPS is still uninvestigated. This study aimed to investigate the mechanisms of bovine serum albumin (BSA) released from poly (D,L-lactic-co-glycolic acid) (PLGA) microspheres prepared by UPPS in comparison with microspheres prepared by the W/O/W double emulsion technique. The morphology, in vitro drug release, water uptake, and structural evolution of microspheres prepared by both techniques were evaluated. UPPS microspheres showed solid and compact internal structures without any pores or channels thereby exhibiting a reduced rate of water permeation in the release medium. In addition, the release of BSA in UPPS microspheres was mainly controlled by the erosion of the polymer matrix during the entire process, while BSA was released from W/O/W microspheres by both drug diffusion and matrix erosion. Moreover, the observed surface and internal structural evolution also confirmed their different release mechanisms. This work elaborates the release mechanism of PLGA microspheres prepared by UPPS and facilitates the design of microparticulate formulations. Graphical abstract.

Mesoporous tablet-shaped potato starch aerogels for loading and release of the poorly water-soluble drug celecoxib

In this study, after determination of the optimal values of the effective parameters in the synthesis using experimental design software, tablet-shaped potato starch aerogels were synthesized at the optimal condition in order to be used as a drug carrier. The celecoxib, as the model drug, was loaded into the aerogel matrix during the solvent exchange step. FTIR (Fourier Transform Infrared Spectroscopy), FESEM and HRTEM (Transmission Electron Microscopy) analyses showed that celecoxib has been successfully loaded into aerogel matrix. Also, XRD analysis showed that most of the celecoxib has been loaded in amorphous form. In vitro studies were performed in both simulated gastric and intestinal fluids. The release kinetics showed that the loaded celecoxib dissolved faster than crystalline celecoxib. At rotational speed of 100 r·min–1, about 26% and 50% and at rotational speed of 50 r·min–1, about 20% and 42% drug was released during the first 30 min of soaking in the simulated gastric fluid and simulated intestinal fluid, respectively. The release of the mentioned drug was increased up to 60% and 98% at a rotational speed of 100 r·min–1 and up to 46% and 93% at a rotational speed of 50 r·min–1 at the end of 5 h in the simulated gastric fluid and simulated intestinal fluid, respectively. It could be concluded that potato starch aerogels can be very useful in many drug delivery applications along with conventional micronization techniques. Modeling of release data showed that the release kinetics follows the Korsmeyer Peppas model, which considers phenomena of matrix erosion and drug diffusion.

Nanocapsule pH Regulator: Sustained Continuous Alkali Release from Thermosensitive Liposomes Reduces Acid Erosion.

Thermosensitive liposomes are major drug delivery carriers, which enable targeting of drugs and burst release of the drugs from the liposomes at the site of action by applying a local heat stimulation above body temperature. Although the burst release is significant for a one-shot high-rate release of drugs at the target site, this type of release has a limited sustained action of the drugs. In this study, we report the alkali-encapsulating thermosensitive liposomes enabling environment pH regulation by sustained continuous cargo release at human body temperature. The liposomes encapsulating alkalis successfully neutralized the environmental acids for hours by releasing the alkalis and prevented acid erosion of hydroxyapatite matrix. Taken together, the present liposomes are effective for the sustained release of cargo at body temperature, specifically the alkali-encapsulating liposomes can be a preventing agent for dental caries in the oral cavity. The sustained release under endogenous body heat characteristics of thermosensitive liposomes showcased in this study can also be extended for prolonged intravenous drug exposure from targeted liposomal drug nanotherapeutics in the near future.

Corn fiber gum-soybean protein isolate double network hydrogel as oral delivery vehicles for thermosensitive bioactive compounds

Corn fiber gum (CFG)-soybean protein isolate (SPI) double network (DN) hydrogels, with varied concentrations of CFG, were fabricated at room temperature in order to develop a biocompatible vehicle for the oral administration of thermosensitive bioactive compounds. Riboflavin (vitamin B2) was encapsulated in the gel as a model bioactive compound. The compound release properties of these DN hydrogels were investigated in simulated gastric and simulated intestinal fluids (SGF and SIF). DN hydrogels with 0.25% of CFG were found to be the most desirable of those assayed for the oral administration of bioactive compounds. The results of low-field nuclear magnetic resonance (LF-NMR) relaxometry measurement showed that the pH-responsive DN hydrogels exhibited low swelling ratio in the SGF but larger swelling ratio in the SIF. The results of degree of proteolysis and scanning electron microscopy (SEM) showed that significant release of riboflavin from DN hydrogels in the SIF was due to large swelling, CFG matrix erosion and the proteolysis of SPI. The release mechanisms of riboflavin through the DN hydrogels in the simulated intestinal fluid followed non-Fickian diffusion based on Peppas' semi-empirical equation.

Controlled Release of Highly Hydrophilic Drugs from Novel Poly(Magnesium Acrylate) Matrix Tablets.

The potential of a new poly(magnesium acrylate) hydrogel (PAMgA) as a pharmaceutical excipient for the elaboration of matrix tablets for the extended release of highly hydrophilic drugs was evaluated. The polymer was synthetized with two different crosslinking degrees that were characterized by FTIR and DSC. Their acute oral toxicity was determined in a mouse model, showing no toxicity at doses up to 10 g/kg. Matrix tablets were prepared using metformin hydrochloride as a model drug and the mechanisms involved in drug release (swelling and/or erosion) were investigated using biorrelevant media. This new hydrogel effectively controlled the release of small and highly hydrophilic molecules as metformin, when formulated in matrix tablets for oral administration. The rate of metformin release from PAMgA matrices was mainly controlled by its diffusion through the gel layer (Fickian diffusion). The swelling capacity and the erosion of the matrix tablets influenced the metformin release rate, that was slower at pH 6.8, where polymer swelling is more intensive, than in gastric medium, where matrix erosion is slightly more rapid. The crosslinking degree of the polymer significantly influenced its swelling capacity in acid pH, where swelling is moderate, but not in intestinal fluid, where swelling is more intense.

Biodegradable Blends of Grafted Dextrin with PLGA-block-PEG Copolymer as a Carrier for Controlled Release of Herbicides into Soil.

The presented work aimed to test influence of poly(L-lactide-co-glycolide)-block-poly (ethylene oxide) copolymer modification by blending with grafted dextrin or maltodextrin on the course of degradation in soil and the usefulness of such material as a matrix in the controlled release of herbicides. The modification should be to obtain homogenous blends with better susceptibility to enzymatic degradation. Among all tested blends, which were proposed as a carrier for potential use in the controlled release of plant protection agents, PLGA-block-PEG copolymer blended with grafted dextrin yielded very promising results for their future applications, and what is very importantly proposed formulations provide herbicides in unchanged form into soil within few months of release. The modification PLAGA/PEG copolymer by blending with modificated dextrins affects the improvement of the release profile. The weekly release rates for both selected herbicides (metazachlor and pendimethalin) were constant for a period of 12 weeks. Enzymatic degradation of modified dextrin combined with leaching of the degradation products into medium caused significant erosion of the polymer matrix, thereby leading to acceleration of water diffusion into the polymer matrix and allowing for easier leaching of herbicides outside the matrix.

Gelatin content governs hydration induced structural changes in silica-gelatin hybrid aerogels – Implications in drug delivery

Silica-gelatin hybrid aerogels of varying gelatin content (from 4 wt.% to 24 wt.%) can be conveniently impregnated with hydrophobic active agents (e.g. ibuprofen, ketoprofen) in supercritical CO2 and used as drug delivery systems. Contrast variation neutron scattering (SANS) experiments show the molecular level hybridization of the silica and the gelatin components of the aerogel carriers. The active agents are amorphous, and homogeneously dispersed in these porous, hybrid matrices. Importantly, both fast and retarded drug release can be achieved with silica-gelatin hybrid aerogels, and the kinetics of drug release is governed by the gelatin content of the carrier. In this paper, for the first time, a molecular level explanation is given for the strong correlation between the composition and the functionality of a family of aerogel based drug delivery systems. Characterization of the wet aerogels by SANS and by NMR diffusiometry, cryoporometry and relaxometry revealed that the different hydration mechanisms of the aerogels are responsible for the broad spectrum of release kinetics. Low-gelatin (4–11 wt.%) aerogels retain their open-porous structure in water, thus rapid matrix erosion dictates fast drug release from these carriers. In contrast to this, wet aerogels of high gelatin content (18–24 wt.%) show well pronounced hydrogel-like characteristics, and a wide gradual transition zone forms in the solid-liquid interface. The extensive swelling of the high-gelatin hybrid backbone results in the collapse of the open porous structure, that limits mass transport towards the release medium, resulting in slower, diffusion controlled drug release. Statement of SignificanceDeveloping new drug delivery systems is a key aspect of pharmaceutical research. Supercritically dried mesoporous aerogels are ideal carriers for small molecular weight drugs due to their open porous structures and large specific surface areas. Hybrid silica-gelatin aerogels can display both fast and retarded drug release properties based on the gelatin contents of their backbones. The structural characterization of the aerogels by SANS and by NMR diffusiometry, cryoporometry and relaxometry revealed that the different hydration mechanisms of the hybrid backbones are responsible for the broad spectrum of release kinetics. The molecular level understanding of the functionality of these hybrid inorganic-biopolymer drug delivery systems facilitates the realization of quality-by-design in this research field.

Design and In-vitro evaluation of gastro retentive drug delivery systems of metoprolol succinate

Gastro retentive drug delivery is a special approach that remains in the stomach for a prolonged period which helps to increase gastric residence time along with site specific drug delivery especially in the upper gastrointestinal tract (GIT) for local or systemic effects. Metoprolol succinate is a beta1-selective adrenergic receptor antagonist used to treat hypertension, angina and arrhythmia. It has a t1/2 of 3-7hrs and is mainly absorbed from the upper parts of GIT with good stability in the acidic environment. The main objective of the present study was to design a floating formulation having Metoprolol succinate as a model drug by using the polymers like HPMC K100M, HPMC K15M, HPMC K4M, Kollidon SR to increase the bioavailability of drug and reduce the dosing frequency. FTIR studies proved that there was no incompatability in the optimized formulations. All the formulations remained buoyant without any disintegration. The formulations F4, F8, F12 and F15 showed similar drug release to that of marketed formulation for a period of 12 hours. To ascertain the mechanism of drug release, in-vitro data was fitted into various release kinetic models like zero order, first order, Higuchi and Peppas. The values indicated, the non fickian diffusion with slow erosion of polymer matrix followed by drug diffusion and resulted in linear drug release profile over a prolonged period of time.

Development of novel bilayer gastroretentive tablets based on hydrophobic polymers.

This study aimed to develop a bilayer gastroretentive (GR) tablet containing an insoluble drug and ascertain the potential of using hydrophobic polymers in GR matrix systems. Highly porous tablets were prepared using a camphor-based sublimation technique. After the screening of several commonly used polymers, two types of GR layers, a conventional hydrophilic GR layer and a hydrophobic GR layer, were designed. The optimal drug layer comprising Metolose® 90SH-100SR and dicalcium phosphate provided not only a gradual matrix erosion but also high strength after hydration. Regarding the GR layers, the hydrophobic layer based on Kollidon® SR was superior to the hydrophilic layer made of PEO 7M in terms of wet strength, implying a higher resistance to mechanical stresses upon water absorption. Also, the excellent tableting properties of Kollidon® SR and the effects of curing in improving its matrix hardness resulted in porous tablets with better mechanical strength. Moreover, good flowability and low cohesion of Kollidon® SR formulation were advantageous in direct compression. In conclusion, novel bilayer GR tablets were successfully developed, indicating the potential for widening the application of GR systems to insoluble drugs. The results also suggested numerous advantages of incorporating Kollidon® SR into the production of GR tablets.

Effect of hygrothermal aging on static behavior of quasi-isotropic CFRP composite laminate

Abstract The Carbon fiber reinforced polymer (CFRP) composites used in offshore and marine industries tend to deal with high temperatures and humid conditions throughout its life. This work investigates the effect of long term hygrothermal aging on the physical and mechanical properties of CFRP composites. The IMA/M21 carbon fiber epoxy quasi-isotropic Multidirectional laminate with stacking sequence [±45, 0, 90] 2S was fabricated using vacuum assisted resin transfer moulding . The static specimens were immersed in room temperature (RT) and comparatively high temperature (HT) tap water at 70 °C up to saturation. The kinetics of moisture absorption was monitored up to saturation as a function of time which followed a two-stage model. The static strength of virgin, RT aged and HT aged specimens were determined with a constant cross-head speed of 1 mm/min. The post-saturation static strength showed a major drop however reduction in compressive strength was higher than tensile strength in a matrix dominated failure. Similarly, the hygrothermal aged specimen showed higher moisture absorption and strength reduction as compared to RT aging. The SEM and FESEM micrographs clearly revealed matrix erosion and fiber-matrix interfacial debonding after saturation. The TGA analysis of the moisture absorbed specimen showed a degraded physical property.

Simulated migrating motor complex and its impact on the release properties of hydrophilic matrix systems

Following ingestion, the dosage forms are exposed to high mechanical stresses, mainly due to the movement of gastric musculature and passage through the sphincters. The generated mechanical forces can have a profound impact on the release properties of the mechanically sensitive formulations, which may result in greater in vivo variability. The aim of the study was to prepare a new programme sequence for our bio-relevant in vitro dissolution model, the advanced gastric simulator (AGS), which would closely resemble the four phases of the migrating motor complex (MMC) and to evaluate the influence of the simulated mechanical stress on the drug release rate and the gel layer properties of the model hydrophilic matrix system. For this purpose, two kinds of HPMC matrix tablets were used, which have previously been tested in vivo. In vivo pressure measurements in human fasted stomach were gathered from literature and compared to the measurements obtained with the wireless motility capsule (WMC) in AGS. Dissolution studies conducted in AGS were compared to the experiments performed in USP2. Properties of the gel layer were evaluated with texture analysis and matrix erosion determination. Our in vitro measured pressure profiles of simulated MMC were found to be within the same range as those observed in vivo. The simulated MMC was shown to significantly affect the drug release kinetics from tested hydrophilic matrices. Compared to USP2, the AGS was shown to have a higher discriminatory power in distinguishing the differences in behaviour of the tested formulations, in accordance with in vivo data.

Casein nanoparticles in combination with 2-hydroxypropyl-β-cyclodextrin improves the oral bioavailability of quercetin.

The aim of this work was to optimize the preparative process of quercetin loaded casein nanoparticles as well as to evaluate the pharmacokinetics of this flavonoid when administered orally in Wistar rats. Nanoparticles were obtained by coacervation after the incubation of casein, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and quercetin in an aqueous environment. Then, nanoparticles were purified and dried. The resulting nanoparticles displayed a size of 200 nm with a negative zeta potential and a payload of about 32 μg/mg. Release studies showed a zero-order kinetic, suggesting a mechanism based on erosion of the nanoparticle matrix. For the pharmacokinetic study, quercetin was orally administered to rats as a single dose of 25 mg/kg. Animals treated with quercetin-loaded casein nanoparticles displayed higher plasma levels than those observed in animals receiving the solution of the flavonoid (control). Thus, the relative oral bioavailability of quercetin when administered as casein nanoparticles (close to 37%) was found to be about 9-times higher than the oral solution of the flavonoid in a mixture of PEG 400 and water. In summary, the combination of casein and 2-hydroxypropyl-β-cyclodextrin produces nanoparticles that may be a good option to load quercetin for both nutraceutical and pharmaceutical purposes.

Development and Characterisation of Gastroretentive Solid Dosage Form Based on Melt Foaming

Dosage forms with increased gastric residence time are promising tools to increase bioavailability of drugs with narrow absorption window. Low-density floating formulations could avoid gastric emptying; therefore, sustained drug release can be achieved. Our aim was to develop a new technology to produce low-density floating formulations by melt foaming. Excipients were selected carefully, with the criteria of low gastric irritation, melting range below 70°C and well-known use in oral drug formulations. PEG 4000, Labrasol and stearic acid type 50 were used to create metronidazole dispersion which was foamed by air on atmospheric pressure using in-house developed apparatus at 53°C. Stearic acid was necessary to improve the foamability of the molten dispersion. Additionally, it reduced matrix erosion, thus prolonging drug dissolution and preserving hardness of the moulded foam. Labrasol as a liquid solubiliser can be used to increase drug release rate and drug solubility. Based on the SEM images, metronidazole in the molten foam remained in crystalline form. MicroCT scans with the electron microscopic images revealed that the foam has a closed-cell structure, where spherical voids have smooth inner wall, they are randomly dispersed, while adjacent voids often interconnected with each other. Drug release from all compositions followed Korsmeyer-Peppas kinetic model. Erosion of the matrix was the main mechanism of the release of metronidazole. Texture analysis confirmed that stearic acid plays a key role in preserving the integrity of the matrix during dissolution in acidic buffer. The technology creates low density and solid matrix system with micronsized air-filled voids.

Investigating release kinetics of phenolics from defatted wheat germ incorporated chewing gums.

Wheat germ (WG) is a valuable by-product of the commercial milling industry and is used as a functional ingredient in various foods. Therefore, in this study, it is aimed to utilize defatted wheat germ (DWG) (1%, 3%, 5%, 10%) in chewing gum formulation, which is a different food matrix besides the conventional structures, and investigate the release kinetics of phenolics from DWG incorporated chewing gums with a new centrifugation method. According to the results, it was observed that DWG was a good source of total phenolics (2254.15 mg GAE kg-1 ). Based on the results obtained from texture profile and sensory analyses, DWG addition did not cause any reverse effect on the chewing gum texture. Centrifugation method was used to indirectly simulate the physical effects of the chewing process. In particular, after 5min of chewing and centrifugation, phenolic release levels were 59.07% and 59.41%, respectively. The model used in the previous studies showed a better correlation than Korsmeyer-Peppas model for ABTS (2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid), CUPRAC (cupric ion reducing antioxidant capacity), and DPPH (2,2-diphenyl-1-picrylhydrazyl) assay results. The results showed that phenolics release from gum base polymer matrix might be dominated by erosion of matrix due to chewing action. Similar phenolic release kinetics were obtained by centrifugation and chewing methods. Therefore, centrifuge equipment can be used to simulate the chewing forces acting on the gum when optimization is performed. © 2019 Society of Chemical Industry.

Synthesis of carboxymethylated nanocellulose fabricated ciprofloxacine - Montmorillonite composite for sustained delivery of antibiotics.

Montmorillonite (MMT) is a highly promising material for use in drug delivery due to its high drug loading capacity and controlled drug release properties. MMT protects drug molecules between layered structure; however, drug release from MMT is sustained less than 6 h, which is insufficient for the release of antibiotics. This study sought to synthesize an antibiotic delivery material with more sustained release properties. A ciprofloxacin (CIP)-MMT composite was fabricated using carboxymethylated nanocellulose (CMCNF). A simple adsorption reaction intercalated 31.1% of CIP molecules present into the MMT under optimized conditions (pH 5, CIP = 1000 mg/L, Reaction time = 3 h). The synthesized CIP-MMT composite was fabricated using 1.5, 2, or 3 wt% CMCNF. Increasing the CMCNF content delayed the erosion of the CMCNF matrix and prevented rapid dissolution of the CIP-MMT composite. In vitro release experiments revealed that the CIP-MMT composite material provided the sustained release of CIP over 6 h. Erosion of the 3 wt% CMCNF-CIP-MMT composite occurred slowly and provided 48 h of sustained CIP release. An anti-bacterial test revealed that the 3 wt% CMCNF-CIP-MMT composite displayed the most constant antibacterial activity over 12 days. These results demonstrated that the CMCNF prepared with CIP intercalation in MMT was highly effective in prolonging the antibiotic release.

Plasticiser-Free 3D Printed Hydrophilic Matrices: Quantitative 3D Surface Texture, Mechanical, Swelling, Erosion, Drug Release and Pharmacokinetic Studies.

Hydroxypropyl methyl cellulose, HPMC, a hydrophilic polymer, is widely used for the development of extended release hydrophilic matrices and it is also considered as a good contender for the fabrication of 3D printing of matrix tablets. It is often combined with plasticisers to enable extrusion. The aim of the current project was to develop plasticizer-free 3D printed hydrophilic matrices using drug loaded filaments prepared via HME to achieve an in vitro (swelling, erosion and drug release) and in vivo (drug absorption) performance which is analogous to hydrophilic matrix tablets developed through conventional approaches. Additionally, the morphology of the printed tablets was studied using quantitative 3D surface texture studies and the porosity calculated. Filaments were produced successfully and used to produce matrix tablets with acceptable drug loading (95–105%), mechanical and surface texture properties regardless of the employed HPMC grade. The viscosity of HPMC had a discernible impact on the swelling, erosion, HPMC dissolution, drug release and pharmacokinetic findings. The highest viscosity grade (K100M) results in higher degree of swelling, decreased HPMC dissolution, low matrix erosion, decreased drug release and extended drug absorption profile. Overall, this study demonstrated that the drug loaded (glipizide) filaments and matrix tablets of medium to high viscosity grades of HPMC, without the aid of plasticisers, can be successfully prepared. Furthermore, the in vitro and in vivo studies have revealed the successful fabrication of extended release matrices.

Do interactions between protein and phospholipids influence the release behavior from lipid-based exenatide depot systems?

The release mechanism for proteins and peptides from vesicular phospholipid gels (VPGs) is very complex. Drug release proceeds via a combination of erosion of the gel and diffusion of the drug out of it. This diffusion can be retarded by a slow permeation of the drug across the lipid bilayers in the gel as well as by its direct binding or adsorption to the lipid bilayers. Finally, the viscosity and homogeneity of the formulation may affect the release behavior. So far a direct correlation between one of these parameters and the release kinetics is not possible.In the present study, we aimed to investigate the contribution of drug-membrane interactions to the release kinetics of exenatide from differently composed VPGs (POPC, POPG and mixtures of both). To this end, in vitro release of exenatide as well as in vitro release of the phospholipids was monitored. Binding affinities were determined by microscale thermophoresis (MST).The sustained release behavior of exenatide could not simply be correlated to high viscosity of the VPG formulation. Release of exenatide from VPGs of anionic membranes containing POPG proceeded with a half-life of the order of 5 days and it seems to be controlled by the erosion of the gel. Its rate is unaffected by the initial pH inside the gel, independently of the strong impact of pH on exenatide binding to the membrane. At pH 4.5, exenatide is cationic and binds to membranes containing anionic POPG with a high affinity (Kd ≈ 10–30 µM).No high affinity membrane binding of exenatide is detected in this at pH 7.4, where exenatide is anionic, and to zwitterionic membranes composed of POPC. Exenatide release from the latter has a significantly longer half-life of 30 to 55 days. That means, these VPGs are much more resistant to erosion and show a very slow diffusional release. In this case, diffusion should be slowed down by the barrier function of the membranes rather than membrane affinity.In conclusion, erosion of the VPG matrix and membrane permeability of the drug are the major parameters influencing the release of exenatide from VPGs of POPC-POPG, whereas drug binding to the membranes had a minor effect only.

Preparation and characterization of Alendronate depot microspheres based on novel poly(-ε-caprolactone)/Vitamin E TPGS copolymers

In the present study, new aledronate (AL) loaded microspheres were prepared with the use of polycaprolactone (PCL)/Vitamin E d-ɑ-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) copolymers. Specifically, PCL-TPGS copolymers, prepared at several PCL to TPGS ratios (namely, 90/10, 80/20, 70/30 and 60/40 w/w) via a ring opening polymerization process, were characterized by intrinsic viscosity, proton nuclear magnetic resonance (1H NMR), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and enzymatic hydrolysis. Results showed that as TPGS content increases the intrinsic viscosity of the copolymer (and hence, the viscosity-average molecular weight) is decreasing, while FTIR analysis showed the formation of hydrogen bonds between the CO of PCL and the OH of TPGS. Additionally, XRD analysis indicated that the prepared copolymers were semi-crystalline in nature, while enzymatic hydrolysis studies showed that increasing TGPS content led to increasing copolymer hydrolysis. In the following step, AL drug-loaded microspheres were prepared via single emulsification process. Scanning electron microscopy (SEM) revealed the formation of coarse drug-loaded microspheres with particle size close to 5 μm, while XRD analysis showed that the API was amorphously dispersed only in the cases of high TPGS content. Furthermore, FTIR analysis showed that the API did not interact with the copolymer components, while in vitro drug release studies showed that increasing PCL content led to decreasing API release rate. Finally, analysis of the drug release profiles suggested that the API release mechanism was solely governed by the polymer matrix erosion.

Release Adjustment of Two Drugs with Different Solubility Combined in a Matrix Tablet

The objective of this study was to modify the release of two drugs having different solubility in a combined matrix tablet as a fixed-dose combination for extended release. Propranolol HCl (freely soluble) and carbamazepine (very slightly soluble) were used as model drugs, water-soluble hydroxypropyl methylcellulose (HPMC) and water-insoluble ethylcellulose (EC) were used as matrix-forming polymers. Tablets were prepared by direct compression of powder blends, or propranolol HCl was first granulated with one of the matrix-forming polymers (1:1) followed by compression with carbamazepine and matrix former. Propranolol HCl release from directly compressed tablets was faster than carbamazepine because of its higher solubility. The release of both drugs was fast when HPMC-propranolol HCl granules were compressed with carbamazepine into EC matrix tablet. Conversely, the release of both drugs was decreased when HPMC-propranolol HCl granules and carbamazepine were compressed into HPMC matrices. The desired release of both drugs was approached when EC-propranolol HCl granules were compressed with carbamazepine into HPMC matrix. Erosion of the HPMC matrix and, therefore, drug release were adjusted by varying the molecular weight of HPMC. A burst release of propranolol HCl decreased when it was granulated with EC in a fluidized bed coater followed by compression with carbamazepine into HPMC matrix.

Influence of vegetation restoration on matrix structure and erosion resistance of iron tailings sites in eastern Hebei, China

The effects of vegetation restoration on matrix structure and erosion resistance of iron tailings were studied at dump sites in Malanzhuang, Qian’an, Hebei province, China. The restoration process involved soil spray sowing restoration model with Rhus typhina, soil and iron tailings admixture spray sowing restoration model with Amorpha fruticosa Linn. and six-hole brick restoration model with Pinus tabulaeformis Carriere.–Amorpha fruticosa Linn. mixed-forest, and direct restoration model with Hippophae rhamnoides and Sabina vulgaris. Results show that the composition and distribution of particles and aggregates were closely related to erosion resistance (P A. fruticosa soil and iron tailings admixture spray sowing > mixed-forest six-hole brick > H. rhamnoides direct restoration > S. vulgaris direct restoration. The R. typhina soil spray sowing restoration model resulted in the greatest improvement in matrix structure of iron tailings, increasing the clay (10.6%) and large particle aggregates (18.7%) contents significantly (P < 0.01). Simultaneously, particle population, grading conditions (Cu = 28.86, Cs = 1.65), and aggregate stability (6.02) were significantly improved. The A. fruticosa soil and iron tailings admixture spray sowing restoration model, which effectively improved particle distribution (Cu = 8.51, Cs = 1.07), increased the number of large aggregates considerably (9.6%), thereby increasing aggregate stability (6.2). The six-hole brick model significantly increased the number of large aggregates (4.0%) and improved the stability of aggregates (6.2). H. rhamnoides direct restoration improved the stability of aggregates (5.1) but showed no other significant improvements. The effect of S. vulgaris direct restoration on matrix structure of iron tailings was not significant. Due to its dependence on matrix structure of iron tailings, the erosion resistance of R. typhina soil spray sowing restoration model was the greatest, while that of S. vulgaris direct restoration was the weakest. There was no significant difference in the erosion resistance of the other models. Overall, vegetation restoration supplemented by soil spray sowing restoration and engineering measures is superior to in situ direct vegetation restoration in the short-term. In-situ direct restoration has long-term ecological significance because of its advanced concept of near-natural restoration and the advantages of low cost, easy operation, and low secondary damage.