Study Of Intestinal Absorption Research Articles

Glyceroniosomes for enhanced intestinal absorption of hydrochlorothiazide and lisinopril in their fixed dose combination.

The objective was to investigate the effect of co-administration of hydrochlorothiazide and lisinopril as fixed dose combination on their intestinal absorption. The scope was extended to enhance intestinal absorption of both drugs. In situ rabbit intestinal absorption through the duodenum and jejuno-ileum was used to monitor membrane permeability of both drugs when perfused alone or in combination. Niosomes containing glycerols (glyceroniosomes) were loaded with both drugs. Glyceroniosomes comprised Span 60 or Tween 40 in combination with cholesterol and glycerol were prepared by bath sonication. Glyceroniosomes were characterized with respect to vesicle size, drug entrapment efficiency and were examined using transmission electron microscope (TEM). The prepared vesicles were nanosized spherical vesicles with average size of 202.4nm and 108.8nm for span free and span containing glyceroniosomes, respectively. The recorded Zeta potential values suggested good stability of the prepared formulations. Intestinal absorption studies reflected incomplete absorption of hydrocholothiazide and lisinopril correlating with their categorization as class IV and III drugs, respectively. Co-perfusion of both drugs reduced the intestinal absorption of lisinopril. Simultaneous encapsulation in glyceroniosomes enhanced the intestinal absorption of both drugs. Tween based systems were more efficient. The study introduced glyceroniosomes as carriers of simultaneous delivery of hydrochlorothiazide and lisinopril.

Cordyceps militaris Grown on Germinated Rhynchosia nulubilis (GRC) Encapsulated in Chitosan Nanoparticle (GCN) Suppresses Particulate Matter (PM)-Induced Lung Inflammation in Mice.

Cordyceps militaris grown on germinated Rhynchosia nulubilis (GRC) exerts various biological effects, including anti-allergic, anti-inflammatory, and immune-regulatory effects. In this study, we investigated the anti-inflammatory effects of GRC encapsulated in chitosan nanoparticles (CN) against particulate matter (PM)-induced lung inflammation. Optimal CN (CN6) (CHI: TPP w/w ratio of 4:1; TPP pH 2) exhibited a zeta potential of +22.77 mV, suitable for GRC encapsulation. At different GRC concentrations, higher levels (60 and 120 mg/mL) led to increased negative zeta potential, enhancing stability. The optimal GRC concentration for maximum entrapment (31.4 ± 1.35%) and loading efficiency (7.6 ± 0.33%) of GRC encapsulated in CN (GCN) was 8 mg/mL with a diameter of 146.1 ± 54 nm and zeta potential of +30.68. In vivo studies revealed that administering 300 mg/kg of GCN significantly decreased the infiltration of macrophages and T cells in the lung tissues of PM-treated mice, as shown by immunohistochemical analysis of CD4 and F4/80 markers. Additionally, GCN ameliorated PM-induced lung tissue damage, inflammatory cell infiltration, and alveolar septal hypertrophy. GCN also decreased total cells and neutrophils, showing notable anti-inflammatory effects in the bronchoalveolar lavage fluid (BALF) from PM-exposed mice, compared to GRC. Next the anti-inflammatory properties of GCN were further explored in PM- and LPS-exposed RAW264.7 cells; it significantly reduced PM- and LPS-induced cell death, NO production, and levels of inflammatory cytokine mRNAs (IL-1β, IL-6, and COX-2). GCN also suppressed NF-κB/MAPK signaling pathways by reducing levels of p-NF-κB, p-ERK, and p-c-Jun proteins, indicating its potential in managing PM-related inflammatory lung disease. Furthermore, GCN significantly reduced PM- and LPS-induced ROS production. The enhanced bioavailability of GRC components was demonstrated by an increase in fluorescence intensity in the intestinal absorption study using FITC-GCN. Our data indicated that GCN exhibited enhanced bioavailability and potent anti-inflammatory and antioxidant effects in cells and in vivo, making it a promising candidate for mitigating PM-induced lung inflammation and oxidative stress.

Human enteroid monolayers as a potential alternative for Ussing chamber and Caco-2 monolayers to study passive permeability and drug efflux.

After oral administration, the intestine is the first site of drug absorption, making it a key determinant of the bioavailability of a drug, and hence drug efficacy and safety. Existing non-clinical models of the intestinal barrier in vitro often fail to mimic the barrier and absorption of the human intestine. We explore if human enteroid monolayers are a suitable tool for intestinal absorption studies compared to primary tissue (Ussing chamber) and Caco-2 cells. Bidirectional drug transport was determined in enteroid monolayers, fresh tissue (Ussing chamber methodology) and Caco-2 cells. Apparent permeability (Papp) and efflux ratios for enalaprilat (paracellular), propranolol (transcellular), talinolol (P-glycoprotein (P-gp)) and rosuvastatin (Breast cancer resistance protein (BCRP)) were determined and compared between all three methodologies and across intestinal regions. Bulk RNA sequencing was performed to compare gene expression between enteroid monolayers and primary tissue. All three models showed functional efflux transport by P-gp and BCRP with higher basolateral to apical (B-to-A) transport compared to apical-to-basolateral (A-to-B). B-to-A Papp values were similar for talinolol and rosuvastatin in tissue and enteroids. Paracellular transport of enalaprilat was lower and transcellular transport of propranolol was higher in enteroids compared to tissue. Enteroids appeared show more region- specific gene expression compared to tissue. Fresh tissue and enteroid monolayers both show active efflux by P-gp and BCRP in jejunum and ileum. Hence, the use of enteroid monolayers represents a promising and versatile experimental platform to complement current in vitro models.

Intestinal absorption studies of ORI-SMEDDS with different zeta potentials through lipolysis absorption model in vitro, single pass intestine perfusion and pharmacokinetics

Intestinal absorption studies of ORI-SMEDDS with different zeta potentials through lipolysis absorption model in vitro, single pass intestine perfusion and pharmacokinetics

Effervescence-induced amorphous solid dispersions with improved drug solubility and dissolution

The current study aimed to investigate drug carrier miscibility in pharmaceutical solid dispersions (SD) and include the effervescent system, i.e. Effervescence-induced amorphous solid dispersions (ESD), to enhance the solubility of a poorly water-soluble Glibenclamide (GLB). Kollidon VA 64, PEG-3350, and Gelucire-50/13 were selected as the water-soluble carriers. The miscibility of the drug-carrier was predicted by molecular dynamics simulation, Hansen solubility parameters, Flory-Huggins theory, and Gibb’s free energy. Solid dispersions were prepared by microwave, solvent evaporation, lyophilization, and Hot Melt Extrusion (HME) methods. The prepared solid dispersions were subjected to solubility, in-vitro dissolution, and other characterization studies. The in-silico and theoretical approach suggested that the selected polymers exhibited better miscibility with GLB. Solid-state characterizations like FTIR and 1H NMR proved the formation of intermolecular hydrogen bonding between the drug and carriers, which was comparatively higher in ESDs than SDs. DSC, PXRD, and microscopic examination of GLB and SDs confirmed the amorphization of GLB, which was higher in ESDs than SDs. Gibb’s free energy concept suggested that the prepared solid dispersions will be stable at room temperature. Ex-vivo intestinal absorption study on optimized ESDs prepared with Kollidon VA64 using the HME technique exhibited a higher flux and permeability coefficient than the pure drug suggesting a better drug delivery. The drug-carrier miscibility was successfully studied in SDs of GLB. The addition of the effervescent agent further enhanced the solubility and dissolution of GLB. Additionally, this might exhibit a better bioavailability, confirmed by ex-vivo intestinal absorption study.

From mouth to gut: microfluidic in vitro simulation of human gastro-intestinal digestion and intestinal permeability.

Reproducible in vitro studies of bioaccessibility, intestinal absorption, and bioavailability are key to the successful development of novel food ingredients or drugs intended for oral administration. There is currently a lack of methods that offer the finesse required to study these parameters for valuable molecules typically found in small volumes - as is the case of nanomaterials, which are often used to carry and protect bioactives. Here, we describe a modular microfluidic-based platform for total simulation of the human gastro-intestinal tract. Digestion-chips and cell-based gut-chips were fabricated from PDMS by soft lithography. On-chip digestion was validated using a fluorescently labelled casein derivative, which followed typical Michaelis-Menten kinetics and showed temporal resolution and good agreement with well-established bench-top protocols. Irreversible inhibition of serine proteases using Pefabloc® SC and a 1 : 6 dilution was sufficient to mitigate the cytotoxicity of simulated digestion fluids. Caco-2/HT29-MTX co-cultures were grown on-chip under a continuous flow for 7 days to obtain a differentiated cell monolayer forming a 3D villi-like epithelium with clear tight junction formation, and with an apparent permeability (Papp) of Lucifer Yellow closely approximating values reported ex vivo (3.7 × 10-6 ± 1.4 × 10-6vs. 4.0 × 10-6 ± 2.2 × 10-6). Digesta from the digestion-chips were flowed through the gut-chip, demonstrating the capacity to study sample digestion and intestinal permeability in a single microfluidic platform holding great promise for use in pharmacokinetic studies.

Oral nanobilosomes of ropinirole: preparation, compatibility and Ex-vivo intestinal absorption study

Oral nanobilosomes of ropinirole: preparation, compatibility and Ex-vivo intestinal absorption study

Aptamer-modified M cell targeting liposomes for oral delivery of macromolecules

There is an urgent demand for non-invasive and high compliance delivery systems of macromolecules for long-term therapy. However, oral administration of macromolecules is hindered by low permeability and instability in the gastrointestinal (GI) tract. Therefore, we developed a novel aptamer-modified liposomes (Apt-Lip) with M cell targeting for oral delivery of exenatide (EXT). Firstly, we optimized aptamers to M cells by Cell-SELEX and aptamer truncations. The selected aptamer T-M3 (Apt-T-M3) with high binding affinity (Kd = 176 ± 108 nM) and specificity was modified on the surface of liposomes for targeting M cells. Liposomes were formulated by microfluidics system and characterized in terms of morphology, hydrodynamic diameter, zeta potential, and the efficiency of encapsulation. In comparison with non-targeting liposomes, cell uptake in M cells was significantly enhanced by Apt-Lip. Similarly, the transport efficiency of EXT was 2-fold increase using Apt-Lip in M cells. Additionally, the transepithelial electrical resistance (TEER) of M cell monolayers is significantly reduced. In ex vivo intestinal absorption study, Apt-Lip was proved to possess significantly high intestinal absorption in Peyer’s patches (PPs) and M cells-specific targeting capacity. Consequently, Apt-Lip promoted the EXT transport could base not only on M cell mediated transport, but also on enhancement of paracellular permeability. In conclusion, the present study supported Apt-Lip as a promising M cell targeted delivery system for oral delivery of macromolecules.

Permeation enhancers loaded bilosomes for improved intestinal absorption and cytotoxic activity of doxorubicin

The clinical utility of doxorubicin is compromised due to dose related toxic side effects and limited oral bioavailability with no oral formulation being marketed. Enhancement of intestinal absorption and magnification of cytotoxicity can overcome these limitations. Accordingly, the objective was to probe penetration enhancers, bilosomes and their combinations for enhanced intestinal absorption and improved cytotoxicity of doxorubicin. Piperine and dipyridamole were tested as enhancers alone or encapsulated in bilosomes comprising Span60, cholesterol and bile salts. Bilosomes were nanosized spherical vesicles with negative zeta potential and were able to entrap doxorubicin with efficiency ranging from 45.3 % to 53 %. Intestinal absorption studies utilized in-situ rabbit intestinal perfusion which revealed site dependent doxorubicin absorption correlating with regional distribution of efflux transporters. Co-perfusion with the enhancer increased intestinal absorption with further augmentation after bilosomal encapsulation. The latter increased the % fraction absorbed by 4.5–6 and 1.8–2.5-fold from jejuno-ileum and colon, respectively, depending on bilosomes composition. Additionally, doxorubicin cytotoxicity against breast cancer cells (MCF-7) was significantly improved after bilosomal encapsulation and the recorded doxorubicin IC50 value was reduced from 13.3 μM to 0.1 μM for the best formulation. The study introduced bilosomes encapsulating absorption enhancers as promising carriers for enhanced cytotoxicity and oral absorption of doxorubicin.

Drug-Carrier Miscibility in Solid Dispersions of Glibenclamide and a Novel Approach to Enhance Its Solubility Using an Effervescent Agent

The present research aims to investigate the miscibility, physical stability, solubility, and dissolution rate of a poorly water-soluble glibenclamide (GLB) in solid dispersions (SDs) with hydrophilic carriers like PEG-1500 and PEG-50 hydrogenated palm glycerides (Acconon). Mathematical theories such as Hansen solubility parameters, Flory Huggins theory, Gibbs free energy, and the in silico molecular dynamics simulation study approaches were used to predict the drug-carrier miscibility. To increase the solubility further, the effervescence technique was introduced to the conventional solid dispersions to prepare effervescent solid dispersions (ESD). Solid dispersions (SDs) were prepared by microwave, solvent evaporation, lyophilization, and hot melt extrusion (HME) techniques and tested for different characterization parameters. The theoretical and in silico parameters suggested that GLB would show good miscibility with the selected carriers under certain conditions. Intermolecular hydrogen bonding between the drug and carrier(s) was confirmed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. Solid-state characterizations like powder X-ray diffraction, differential scanning calorimetry, and microscopy confirm the amorphous nature of SDs. The addition of the effervescent agent improved the amorphous nature, due to which the solubility and drug release rate was increased. In vitro and ex vivo intestinal absorption studies showed improved flux and permeability than the pure drug, suggesting an enhanced drug delivery. The GLB solubility, dissolution, and stability were greatly enhanced by the SD and ESD technology.Graphical

Stable Amorphous Solid Dispersion of Eplerenone Prepared with Water Soluble Polymer by Spray Drying Technique

Class II in the Biopharmaceutical Classification System, eplerenone (EPL) is a selective aldosterone antagonist. Due to its poor solubility, EPL has limited bioavailability. Here, an innovative spray-drying method was used to transform a water soluble polymer into an amorphous dispersion of the EPL. Different polymer SOL/EPL ratios were tested to determine EPL’s solubility and dissolution enhancement properties. In order to learn more about the physical and chemical properties of this novel amorphous solid dispersion (ASD), methods like powder X-ray diffraction spectroscopy (PXRD), differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), particle size distribution (PSD) using a Malvern instrument, and scanning electron microscopy (SEM) were used. There was no chemical interaction between the binary mixture of EPL and SOL which was confirmed from the FTIR spectra obtained. The enhancement in the solubility and dissolution of EPL and binary mixture prepared were due to the amorphous conversion of EPL in the SOL polymer (amorphous solid dispersion), which was confirmed from DSC thermogram, PXRD spectra obtained and was also confirmed from the solubility study, in-vitro dissolution study. Finally, ex-vivo intestinal absorption study performed on the goat intestine using amorphous solid dispersion and pure EPL, also improved intestinal absorption of EPL through amorphous solid dispersion prepared.

Dissolution enhancement of Enzalutamide by solid dispersion approach

Enzalutamide (ENZ) is a BCS class II, fast crystallizing, a hydrophobic compound that has solubility limited absorption in vivo. Ternary solid dispersion of Enzalutamide was prepared with water-soluble polymers Soluplus (SOL) and Poloxamer P 188 (POL) by solvent evaporation spray drying technique. Initially, different ratios of Soluplus: Poloxamer and solvents were used to prepare Ternary solid dispersions of Enzalutamide and evaluated for the dissolution enhancement property. The prepared solid dispersion was characterized by FTIR spectroscopy, Differential scanning calorimetry (DSC), X-ray diffraction (XRD) analysis, Scanning electron microscopy (SEM), Particle size distribution (PSD) by Malvern and Physico-chemical analysis. FTIR spectroscopy shows that there was no interaction between the ENZ and polymers. DSC and XRD analysis show that conversion to amorphous form of ENZ in ternary SD, which enhances the dissolution rate. In vitro dissolution studies and Ex-vivo intestinal absorption studies clearly show that the prepared solid dispersion enhanced the dissolution and ex-vivo intestinal absorption of ENZ compared with pure ENZ.

Simultaneous Determination of Ten Active Components From Jinhongtang Granule in Rat Plasma by LC-MS/MS and its Application to a Comparative Pharmacokinetic Study in Normal and Sepsis Rats In Vivo and In Vitro.

Jinhongtang granule (JHT) is a traditional Chinese medicine formula used for treatment of infection diseases including severe COVID-19. However, pharmacokinetics of JHT was unknown, especially in infection condition. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously quantify ten active components form JHT in rat plasma. MS detection was performed by MRM scanning operating in the negative ionization mode. The method showed good linearity (r > 0.997). The accuracy, precision, matrix effect, recovery and stability were all satisfactory with current criterion. The method was successfully applied to compare the pharmacokinetic difference between normal and sepsis rats. The pharmacokinetic behaviors of analytes in sepsis rats were significantly different from those in normal rats. Cmax and AUC of rhein, emodin, aloe emodin, rhein-8-glucoside, aloe emodin 8-glucoside, protocatechuic acid, epicatechin and salidroside, were significantly increased in sepsis rats, except for 4-hydroxycinnamic acid and ferulic acid. In vitro intestinal absorption study using everted intestinal sac preparations indicated that the intestinal permeability was altered under sepsis. In conclusion, pharmacokinetic difference of JHT between normal and sepsis rats were evaluated for the first time, which provided useful information for the clinical application of JHT as an integrative therapy for severe and critical COVID-19.

Ibuprofen Loaded Electrospun Polymeric Nanofibers: A Strategy to Improve Oral Absorption.

The poor aqueous solubility of candidate drugs has presented a great challenge to formulation scientists for their effective oral delivery. Poor solubility is often associated with poor dissolution behavior and, subsequently, poor bioavailability for those drugs when intestinal absorption is dissolution rate limited. In the present study electrospun polymeric nanofibers were developed to address the poor aqueous solubility of ibuprofen, a Biopharmaceutic Classification System (BCS) class-II drug. Hydrophilic spinnable polymers like polyvinyl pyrrolidone were deployed as a carrier system for the fabrication of nanofibers. The electrospinning parameters like flow rate, voltage, and spinneret to collector distance were optimized. The fabricated ibuprofen-loaded nanofibers were characterized using scanning electron microscopy and differential scanning calorimetry. Drug release studies and ex vivo intestinal absorption studies were also carried out. The nanofiber-based platform significantly improved in vitro absorption of ibuprofen compared to pure ibuprofen crystals.

Intestinal Absorption Study of a Granular Form of Ferric Pyrophosphate.

Iron deficiency is one of the most prevalent nutritional disorders worldwide. The standard treatment involves iron supplementation, but this task is challenging because of poor solubility and organoleptic issues. Moreover, the need to increase iron bioavailability represents a challenge for treating iron-related disorders. In this study, gastroresistance and iron intestinal absorption of an innovative granular formulation composed of ferric pyrophosphate, modified starch and phospholipids branded as Ferro Fosfosoma® was investigated. Gastroresistant properties were studied using standard protocols, and a bioaccessible fraction was obtained by exposing a food supplement to in vitro digestion. This fraction was used for investigating iron absorption in Caco-2 and human follicle-associated intestinal epithelium (FAE) models. Ferro Fosfosoma® showed an improved resistance to gastric digestion and higher intestinal absorption than ferric pyrophosphate salt used as a control in both models. In the FAE model, Ferro Fosfosoma® induces larger iron absorption than in the Caco-2 monolayer, most likely due to the transcytosis ability of M cells. The larger iron absorption in the Ferro Fosfosoma®-treated FAE model corresponds to higher ferritin level, proving physiological iron handling that was once delivered by granular formulation. Finally, the formulation did not induce any alterations in viability and barrier integrity. To conclude, Ferro Fosfosoma® favors iron absorption and ferritin expression, while preserving any adverse effects.

Bromelain Loaded Lipid-Polymer Hybrid Nanoparticles for Oral Delivery: Formulation and Characterization.

Bromelain (Br), a mixture of proteolytic enzymes from pineapple (Ananas comosus), has various therapeutic potentials; however, its low bioavailability has limited the clinical applications specifically in oral delivery as the most common convenient used route of administration. In the present study, a lipopolymeric nanoparticle (NP) containing Br was developed to enhance its stability and oral delivery efficiency. Firstly, Br was loaded into poly (D, L-lactide-co-glycolide acid) (PLGA) and PLGA-phosphatidylcholine (PLGA-PC) NPs using double emulsion solvent evaporation technique. Then, Br integrity and activity were investigated using SDS-PAGE and gelatin test. The stability and release profile of Br from synthetized NPs were evaluated at different pH values of the digestive system. Furthermore, cytotoxicity, cellular uptake, and the amount of Br passage from Caco-2 cells were explored. The results showed PLGA-PC-Br NPs had higher encapsulation efficiency (83%) compared to PLGA-Br NPs (50%). In addition, this NP showed more Br released in neutral (20.36%) and acidic (34%) environments compared to PLGA-Br NPs after 5 days. The delay in the release of Br from PLGA-PC-Br NPs versus the faster release of Br from PLGA-Br formulation could assure that an appropriate concentration of Br has reached the intestine. Intestinal absorption study demonstrated that lipid polymer NPs were able to pass through Caco-2 cells about 1.5 times more (98.4%) than polymeric NPs (70%). In conclusion, PLGA-PC NPs would be considered as a promising lipid-polymer nanocarrier for effective intestinal absorption of Br.

In vitro Bioaccessibility and Intestinal Absorption of Selected Bioactive Compounds in Terminalia ferdinandiana.

Terminalia ferdinandiana (or Kakadu plum), a native Australian fruit with potential health benefits, contains bioactive compounds such as ellagic acid (EA), ascorbic acid (AA) and calcium, and antinutrients such as oxalic acid (OA). However, few is known about the biological fate of these compounds following ingestion; therefore, the aim of this study was to evaluate in vitro bioaccessibility and intestinal absorption of T. ferdinandiana compounds using the INFOGEST static digestion model and Caco-2-HT29-MTX-E12 intestinal absorption model. No significant changes (p > 0.05) were observed in total AA content throughout in vitro digestion, whereas bioaccessibility of EA, OA, and calcium increased significantly from 33, 72, and 67% in the gastric phase to 48, 98, and 90% in the intestinal phase, respectively. The intestinal absorption study revealed variable rates of movement across the cell barrier. Findings reveal novel and important insights for the prediction of in vivo bioavailability of selected T. ferdinandiana compounds.

Studies on absorption and transportation of coumarins in Angelica dahurica 'Yubaizhi' across human intestinal epithelial by using human Caco-2 cell monolayers

The absorption is the key to the resulted efficacy of orally administered drugs and the small intestine is the main site to absorb the orally administered drug. In this paper, internationally recognized human colon adenocarcinoma cell line(Caco-2) monola-yer model which can simulate small intestinal epithelial cell was used to comparatively study the absorption and transportation diffe-rences of total coumarins and main individual coumarin in Angelica dahurica 'Yubaizhi' by separately using 6-and 12-well plates. It was found that apparent permeability coefficient(P_(app)) values of oxypeucedanin hydrate, byakangelicin and phellopterin were at the quantitative degree of 1 × 10~(-5) cm·s~(-1) when the individual administration was conducted independently, indicating that they were well-absorbed compounds. P_(app) ratio of their bi-directional transportation was close to 1, indicating that they can be absorbed across Caco-2 monolayer by passive diffusion mechanism without carrier mediation during the transportation. The similar trend of transportation was also observed for imperatorin, isoimperatorin and bergapten. The P_(app) values of oxypeucedanin hydrate, byakangelicin and bergapten were at quantitative degree of 1 × 10~(-5) cm·s~(-1) when the administration of total coumarins in Angelica dahurica 'Yubaizhi' was conducted, indicating that they were well-absorbed compounds. The results were consistent with those of independent administration of individual coumarins. Whereas, the P_(app) values of imperatorin, phellopterin and isoimperatorin in the total coumarins decreased, indicating that the interaction between compounds may exist although the P_(app) value ratio of bi-directional transportation was between 0.5 and 1.5. The results laid the foundation for intestinal absorption study of Angelica dahurica 'Yubaizhi' coumarins in compound Chinese medicine.

A novel zinc complex with antibacterial and antioxidant activity

BackgroundIn order to enhance the antibacterial activity and reduce the toxicity of Zn2+, novel complexes of Zn(II) were synthesized.ResultsA water-soluble zinc-glucose-citrate complex (ZnGC) with antibacterial activity was synthesized at pH 6.5. The structure, morphology, characterization, acute toxicity, antibacterial and antioxidant activities, and in situ intestinal absorption were investigated. The results showed that zinc ion was linked with citrate by coordinate bond while the glucose was linked with it through intermolecular hydrogen bonding. The higher the molecular weight of sugar is, the more favorable it is to inhibit the formation of zinc citrate precipitation. Compared with ZnCl2, ZnGC complex presented better antibacterial activity against Staphylococcus aureus (S. aureus, Gram-positive) and Escherichia coli (E. coli, Gram-negative).ConclusionsThe results of acute toxicity showed no obvious toxicity in this test and in situ intestinal absorption study, suggesting that ZnGC complex could be used as a potential zinc supplement for zinc deficiency.

Improved Dissolution Rate and Intestinal Absorption of Fexofenadine Hydrochloride by the Preparation of Solid Dispersions: In Vitro and In Situ Evaluation.

The objective of this study was to enhance dissolution and permeation of a low soluble, absorbable fexofenadine hydrochloride (FFH) by preparing solid dispersions using polyethylene glycol 20,000 (PEG 20,000) and poloxamer 188 as carriers. The phase solubility measurement for the supplied FFH revealed a linear increase in the solubility of fexofenadine with increasing carrier concentration in water (1.45 mg/mL to 11.78 mg/mL with 0% w/v to 30% w/v PEG 20,000; 1.45 mg/mL to 12.27 mg/mL with 0% w/v to 30% w/v poloxamer 188). To select the appropriate drug carrier concentration, a series of solid dispersions were prepared in the drug carrier weight ratios of 1:1, 1:2 and 1:4 by fusion method. The solid dispersions composed of drug carrier at 1:4 weight ratio showed highest dissolution with the time required for the release of 50% of the drug <15 min compared to the supplied FFH (>120 min). The intestinal absorption study presented a significant improvement in the absorption of drug from the solid dispersions composed of poloxamer 188 than PEG 20,000. In summary, the solid dispersions of FFH prepared using PEG 20,000 and poloxamer 188 demonstrated improved dissolution and absorption than supplied FFH and could be used to improve the oral bioavailability of fexofenadine.