Improved solubility and oral bioavailability of apigenin via Soluplus/Pluronic F127 binary mixed micelles system

The aim of this study was to develop a novel mix micelles system composing of two biocompatible copolymers of Soluplus^® and Pluronic F127 to improve the solubility, oral bioavailability of insoluble drug apigenin (AP) as model drug. The AP-loaded mixed micelles (AP-M) were prepared by ethanol thin-film hydration method. The formed optimal formulation of AP-M were provided with small size (178.5?nm) and spherical shape at ratio of 4:1 (Soluplus^®:Pluronic F127), as well as increasing solubility of to 5.61?mg/mL in water which was about 3442-fold compared to that of free AP. The entrapment efficiency and drug loading of AP-M were 95.72 and 5.32%, respectively, and a sustained release of AP-M was obtained as in vitro release study indicated. Transcellular transport study showed that the cell uptake of AP was increased in Caco-2 cell transport models. The oral bioavailability of AP-M was 4.03-fold of free AP in SD rats, indicating the mixed micelles of Soluplus^® and Pluronic F127 is an industrially feasible drug delivery system to promote insoluble drug oral absorption in the gastrointestinal tract.     

Self-emulsifying bifendate pellets: preparation,characterization and oral bioavailability in rats

In this study, a self-emulsifying pellet (SEP) was prepared in order to improve the bioavailability of bifendate (DDB). First, a liquid self-emulsifying drug delivery system (SEDDS) was formulated, and then further developed into the SEP by extrusion/spheronization technology using the reconstituted emulsion as the adhesive. The optimized liquid SEDDS consisted of Miglycol^® 840, a mixture of Cremorphor^® EL and Solutol HS^® 15 (1:2, w/w), and Transcutol HP as the oil phase, the surfactant and the co-surfactant at a weight ratio of 40:45:15 (w/w/w), respectively. The SEP were prepared using a mixture of MCC, lactose, and mannitol (45:45:10, w/w/w) as solid adsorbents. The SEP with 40% (w/w) of the liquid SEDDS was round-shaped with a uniform size (800–1000 µm). There was no difference in droplet size between the emulsions obtained from the liquid SEDDS or the SEP (169.8 ± 6.3 nm and 163.7 ± 3.8 nm). Compared with that of DDB pills (less than 20%), in vitro release of DDB from the SEP (over 80% within 60 min) was significantly enhanced in 0.1N HCl, although slower than that of the liquid SEDDS (over 80% within 5 min). AUC of DDB of the SEP after oral administration in rats exhibited 2.36-fold greater than that of DDB pills and no significant difference compared with that of the liquid SEDDS. In conclusion, our studies illustrated that extrusion/spheronization technique could be a useful method to prepare this SEP and it could be a promising way for enhancing oral bioavailability of poorly water-soluble drugs.     

Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation,characterization, plasma,and kidney pharmacokinetics

The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6?±?5.95?nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71?±?3.02%, and the drug loading was 1.56?±?0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUC_kidney/AUC_plasma?=?0.586?±?0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.     

Improved oral bioavailability of fexofenadine hydrochloride using lipid surfactants: ex vivo,in situ and in vivo studies

The aim of the present study was to improve the dissolution, permeability and therefore oral bioavailability of the fexofenadine hydrochloride (FEX), by preparing lipid surfactant based dispersions using self-emulsifying carriers, i.e. Gelucire 44/14 (GLC) and d-α-tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS or TPGS). The reprecipitation studies were conducted using these carriers to evaluate inhibition of reprecipitation by maintaining super saturation state. The aqueous solubility of the FEX was increased linearly with increasing GLC, TPGS concentrations as verified by the phase solubility studies. The dispersions of FEX were prepared in different drug/GLC (GD) and drug/TPGS (TD) ratios by melt method and evaluated. The prepared dispersions showed improved dissolution rate in distilled water as dissolution media and highest dissolution rate was achieved with dispersions prepared using TPGS. The solid state characterization was carried by differential scanning calorimetry and scanning electron microscopy indicated reduced crystallinity of the drug. Fourier transform infrared spectroscopy revealed the compatibility of drug with carriers. The ex vivo permeation studies conducted using intestinal gut sac technique, resulted in reduced efflux of the drug by inhibiting intestinal P-glycoprotein from the dispersions. The in situ perfusion studies and in vivo pharmacokinetic studies in male wistar rats showed improved absorption and oral bioavailability from the prepared dispersions as compared to pure drug.     

Improved dissolution rate and bioavailability of fenofibrate pellets prepared by wet-milled-drug layering

Objective: The objective of this study is to investigate the wet-milled-drug layering process which could significantly improve the dissolution rate and oral bioavailability of fenofibrate pellets.

Methods: Fenofibrate was milled with HPMC-E5 to prepare a uniform suspension in the micrometer and nanometer range, and this suspension was then layered on to sugar spheres to form the pellets (F1, F2).

Results: The particle size was significantly reduced (from 1000 µm to 1–10 µm and 400?nm) but the fenofibrate in suspension retained its crystallinity from the results of DSC and PXRD investigations. The dissolution rate of F1-F2 and Antara® capsules was 55.47 %, 61.27 % and 58.43 %, respectively, in 0.01?mol/L SDS solution over 60?min. In addition, F1, F2, and Antara® capsules were given orally to 6 beagle dogs to determine the bioavailability. The C_max of F1, F2 (8.21?±?2.55 and 9.33?±?2.37 μg/mL)and the AUC_(0?t) of F1, F2 (152.46?±?78.89 and 172.17?±?67.58 μg/mL·h)were higher than those of Antara® (6.02?±?3.34 μg/mL and 89.82?±?46.46 μg/mL·h) and, F1, F2 reached their C_max earlier than Antara® (F1: 2.0?±?1.1?h; F2: 1.8?±?1.2?h; Antara®: 6.0?±?8.9?h).

Conclusion: These results show that the wet-milled-drug layering technique is a powerful method to improve the dissolution rate and the bioavailability of fenofibrate.     

Production and characterization of testosterone undecanoate-loaded NLC for oral bioavailability enhancement

Purpose: Nanostructured lipid carriers were loaded with testosterone undecanoate (TU), which has a low oral bioavailability. Methods: Different NLC dispersions were produced using the hot high pressure homogenization method. Particles were characterized using dynamic and static light scattering techniques, differential scanning calorimetry and X-ray diffraction. And the bioavailability was compared to a marketed product. Results: Nanostructured lipid carriers with up to 30% TU load and sizes of about 600 and 200 nm could be achieved, allowing a direct comparison of the size effect in in vivo bioavailability studies. The zeta potentials varied between ??20 and ??40 mV. The bioavailability of Andriol Testocaps® in the fed state was matched. Conclusions: This opens the perspective of administering a single dose of dose of TU in one oral dosage unit and simultaneously having a bioavailability less dependent on the fed state.     

Enhance the dissolution rate and oral bioavailability of pranlukast by preparing nanosuspensions with high-pressure homogenizing method

Purpose: Pranlukast, one of the potential therapeutic tools in the treatment of asthma, has limited clinical applications due to its poor water solubility. The study is aimed to provide a platform for better utilizing pranlukast with enhancement of the dissolution rate and, thus, the oral bioavailability of pranluka’st by preparing nanosuspensions through high-pressure homogenization method.

Method: Poloxamer407 and PEG200 were chosen as stabilizer and surfactant. The formulation was investigated systematically with the dissolution tests as predominant method. Nanosuspensions were prepared by programmed high-pressure homogenization method. The product was characterized by particle size analysis, TEM and XRD are evaluated by in vitro dissolution tests and in vivo absorption examination. In addition, nanosuspensions with only pranlukast were prepared and compared with formulated nanosuspensions.

Results: The optimal values of formulation were 0.5% (w/v) pranlukast with 0.375% (w/v) Poloxamer407, 0.375% (w/v) PEG200 and the screened programming homogenizing procedure parameters were 680 bar for the first 15 circles, 1048 bar for the next 9 circles and 1500 bar for the last 9 circles. Nanosuspensions of 318.2?±?7.3?nm, ?29.3?±?0.8 mV were obtained. The XRD analysis indicated no change of crystalline occurred in the process of homogenization. The in vitro dissolution behavior of nanosuspensions exhibited complete release in 30?min with a remarkable fast dissolution rate. The in vivo bioavailability of formulated pranlukast nanosuspensions demonstrated its enhancement of fast onset of therapeutic drug effects with 4.38-fold improved compared to that of raw crystals.

Conclusion: The study provides a feasible, practical thinking of industry development in the clinical use of pranlukast.     

Enhancement of the oral bioavailability of breviscapine by nanoemulsions drug delivery system

Aim to design an effective breviscapine nanoscale drug delivery system to realize the improvement of its oral bioavailability. Based on the investigations of the stabilities in the gastrointestinal tract (GIT), permeation and efflux across the cell membrane, the breviscapine nanoemulsion (NE) was formulated and evaluated in vitro and in vivo. The globule size and polydispersity index of the NE was 45.6?nm and 0.105, and the efficient encapsulation was 95.2%. In vitro, the drug release from NEs in pH 6.8 PBS fit to the first-order kinetics. The Caco-2 cell transport experiments showed that the breviscapine NE facilitated the improvement of the apparent permeability coefficient (P_app) from the apical side to basilar side compared with the free drug. In vivo, the relative bioavailability of breviscapine NE reached to 249.7%. All the studies implicated that the NE carrier contributed to the enhancement of the oral absorption of breviscapine due to the improved stability and permeation in the GIT. The nanoemulsions technology is better for the poor permeable and unstable active agents in GIT as well as helps the industrial scale process.     

Low molecular weight chitosan-based conjugates for efficient Rhein oral delivery: synthesis,characterization, and pharmacokinetics

Objective: This article aims to design low molecular weight chitosan (LMWC)-based conjugates of Rhein (RH) by means of an amino acid linker (Alanine) for improved solubility and enhanced bioavailability.

Significance: Rhein is a potential candidate for the therapy of kidney disease. However, the poor solubility, inadequate bioavailability, and lack of proper formulation restrict its clinical applicability. LMWC-drug conjugates offer the potential to improve the water-solubility of RH, increase its oral absorption, and thereby enhance its bioavailability.

Methods: The conjugates were synthesized via a carbodiimide reaction and confirmed using UV-vis, FTIR, and ¹H-NMR spectroscopy. The water-solubility and in vitro release properties were evaluated. Free RH and RH-LMWC conjugates were administered at an equivalent oral gavage dose of RH at 35?mg/kg for pharmacokinetic studies in Sprague Dawley rats.

Results: The conjugates with RH content of 9.65% were successfully synthesized and featured a satisfactory water-solubility of 9.73?mg/mL, which exhibited a sustained release pattern over 72?h, and the enzymes present may promote the degradation of the conjugate to increase the release of Rhein. Oral administration of RH-LMWC conjugates to rats led to seven-folds and 3.1-folds increase in the T_1/2 and AUC_0–∞, respectively, as compared to RH suspension.

Conclusion: The present work demonstrated that the RH-LMWC conjugates exhibited sustained release properties with outstanding oral bioavailability enhancements compared to administration of RH itself. Potentially, RH-LMWC conjugates may serve as a promising lead for developing a new platform for RH oral delivery.     

Enhanced oral bioavailability and sustained delivery of glimepiride via niosomal encapsulation: in-vitro characterization and in-vivo evaluation

This study was designed to investigate the potency of niosomes, for glimepiride (GLM) encapsulation, aiming at enhancing its oral bioavailability and hypoglycemic efficacy. Niosomes containing nonionic surfactants (NIS) were prepared by thin film hydration technique and characterized. In-vitro release study was performed using a dialysis technique. In-vivo pharmacodynamic studies, as well as pharmacokinetic evaluation were performed on alloxan-induced diabetic rats. GLM niosomes exhibited high-entrapment efficiency percentages (E.E. %) up to 98.70% and a particle size diameter ranging from 186.8?±?18.69 to 797.7?±?12.45?nm, with negatively charged zeta potential (ZP). Different GLM niosomal formulation showed retarded in vitro release, compared to free drug. In-vivo studies revealed the superiority of GLM niosomes in lowering blood glucose level (BGL) and in maintaining a therapeutic level of GLM for a longer period of time, as compared to free drug and market product. There was no significant difference between mean plasma AUC_0-48?hr of GLM-loaded niosomes and that of market product. GLM-loaded niosomes exhibited seven-fold enhancement in relative bioavailability in comparison with free drug. These findings reinforce the potential use of niosomes for enhancing the oral bioavailability and prolonged delivery of GLM via oral administration.     

Application of scCO2 technology for preparing CoQ10 solid dispersion and SFC-MS/MS for analyzing in vivo bioavailability

Objective: In this study, solid dispersion (SD) for oral delivery of a poorly water-soluble drug, coenzyme Q10 was developed by supercritical fluid technology and characterized in vitro and in vivo.

Methods: Dissolution was used to optimize the formulations of CoQ10-SD. The physicochemical properties of SD were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The supercritical fluid chromatography–electrospray ionization tandem mass spectrometry (SFC–ESI-MS/MS) was used for the in vivo study.

Results: The results of DSC and PXRD indicated that the drug in SD was in amorphous state. In vitro drug release, the dissolution of coenzyme Q10 in solid dispersion improved to 78.8% compared with commercial tablets of 0.16%. The area under c–t curve (AUC_0–72h) and mean maximum concentrations (C_max) of CoQ10-SD were 2.43-fold and 3.0-fold, respectively higher than that of commercial tablets in rats, confirming improved bioavailability.

Conclusion: Supercritical fluid technology was successfully used for the preparation and analysis of CoQ10-SD for the first time and significantly improved the dissolution and bioavailability of coenzyme Q10.     

Gastrointestinal stability,physicochemical characterization and oral bioavailability of chitosan or its derivative-modified solid lipid nanoparticles loading docetaxel

Abstract

Objective: The purpose of this study was to prepare the positively charged chitosan (CS)- or hydroxypropyl trimethyl ammonium chloride chitosan (HACC)-modified solid lipid nanoparticles (SLNs) loading docetaxel (DTX), and to evaluate their properties in vitro and in vivo.

Methods: The DTX-loaded SLNs (DTX-SLNs) were prepared through an emulsion solvent evaporation method and further modified with CS or HACC (CS-DTX-SLNs or HACC-DTX-SLNs) via noncovalent interactions. The gastrointestinal (GI) stability, dissolution rate, physicochemical properties and cytotoxicities of SLNs were investigated. In addition, the GI mucosa irritation and oral bioavailability of SLNs were also evaluated in rats.

Results: The HACC-DTX-SLNs were highly stable in simulated gastric and intestinal fluids (SGF and SIF). By contrast, the CS-DTX-SLNs were less stable in SIF than in SGF. The drug dissolution remarkably increased when DTX was incorporated into the SLNs, which may be attributed to the change in the crystallinity of DTX and some molecular interactions that occurred between DTX and the carriers. The SLNs showed low toxicity in Caco-2 cells and no GI mucosa irritations were observed in rats. A 2.45-fold increase in the area under the curve of DTX was found in the HACC-DTX-SLN group compared with the DTX group after the modified SLNs were orally administered to rats. However, the oral absorption of DTX-SLN or CS-DTX-SLN group showed no significant difference compared with that of DTX group.

Conclusions: The positively charged HACC-DTX-SLNs with a stable particle size could provide the enhanced oral bioavailability of DTX in rats.     

Fabrication of solid lipid nanoparticles of lurasidone HCl for oral delivery: optimization,in vitro characterization,cell line studies and in vivo efficacy in schizophrenia

Objective: The aim of the present investigation was to investigate the efficacy of solid lipid nanoparticles (SLNs) to enhance the absorption and bioavailability of lurasidone hydrochloride (LH) following oral administration.

Methods: The LH loaded SLNs (LH-SLNs) were prepared by high pressure homogenization (HPH) method, optimized using box Behnken design and evaluated for particle size (PS), entrapment efficiency (EE), morphology, FTIR, DSC, XRD, in vitro release, ex vivo permeation, transport studies across Caco-2 cell line and in vivo pharmacokinetic and pharmacodynamic studies.

Results: The LH-SLNs had PS of 139.8?±?5.5?nm, EE of 79.10?±?2.50% and zeta potential of ?30.8?±?3.5?mV. TEM images showed that LH-SLNs had a uniform size distribution and spherical shape. The in vitro release from LH-SLNs followed the Higuchi model. The ex vivo permeability study demonstrated enhanced drug permeation from LH-SLNs (>90%) through rat intestine as compared to LH-suspension. The SLNs were found to be taken up by energy dependent, endocytic mechanism which was mediated by clathrin/caveolae-mediated endocytosis across Caco-2 cell line. The pharmacokinetic results showed that oral bioavailability of LH was improved over 5.16-fold after incorporation into SLNs as compared to LH-suspension. The pharmacodynamic study proved the antipsychotic potential of LH-SLNs in the treatment of schizophrenia.

Conclusion: It was concluded that oral administration of LH-SLNs in rats improved the bioavailability of LH via lymphatic uptake along with improved therapeutic effect in MK-801 induced schizophrenia model in rats.     

Enhanced oral delivery and anti-gastroesophageal reflux activity of curcumin by binary mixed micelles

The aim of this study was to improve the solubility, oral bioavailability, and anti-gastroesophageal reflux activity of curcumin (CM) by preparing two CM-loaded, novel, binary mixed micelles (CM-M). The two CM-M were prepared by ethanol thin-film hydration method. One (CM-T) was prepared using D-alpha-tocopheryl polyethylene glycol 1000 succinate and Solutol^®HS15, and the other (CM-F) was prepared using Pluronic^®F127 and Solutol^®HS15. The entrapment efficiency and drug loading of CM-T were 83.61?±?0.54% and 2.20?±?0.65%, respectively, which were lower than those of CM-F (88.66?±?0.12% and 1.47?±?0.26%, respectively). TEM results demonstrated that CM-T and CM-F were homogeneous and spherical. The permeability of CM delivered via CM-T and CM-F was enhanced across a Caco-2 cell monolayer, and CM-T and CM-F showed a 5.24- and 4.76-fold increase in relative oral bioavailability, respectively compared with free CM. In addition, the in vivo anti-gastroesophageal reflux study showed that CM-T and CM-F achieved higher anti-gastroesophageal reflux efficacy compared with free CM. Collectively, these findings were indicative of an oral micelle formulation of CM with increased solubility, oral bioavailability, and anti-gastroesophageal reflux activity.     

Enhancing oral bioavailability of poorly soluble drugs with mesoporous silica based systems: opportunities and challenges

Porous silica-based drug delivery systems have shown considerable promise for improving the oral delivery of poorly water-soluble drugs. More specifically, micro- and meso-porous silica carriers have high surface areas with associated ability to physically adsorb high-drug loads in a molecular or amorphous form; this allows molecular state drug release in aqueous gastrointestinal environments, potential for supersaturation, and hence facilitates enhanced absorption and increased bioavailability. This review focuses primarily on the ability of porous silica materials to modulate in vitro drug release and enhance in vivo biopharmaceutical performance. The key considerations identified and addressed are the physicochemical properties of the porous silica materials (e.g. the particle and pore size, shape, and surface chemistry), drug specific properties (e.g. pKa, solubility, and nature of interactions with the silica carrier), potential for both immediate and controlled release, drug release mechanisms, potential for surface functionalization and inclusion of precipitation inhibitors, and importance of utilizing relevant and effective in vitro dissolution methods with discriminating dissolution media that provides guidance for in vivo outcomes (i.e. IVIVC).     

Chitosan nanoparticles for the oral delivery of tenofovir disoproxil fumarate: formulation optimization,characterization and ex vivo and in vivo evaluation for uptake mechanism in rats

Objective: Design chitosan based nanoparticles for tenofovir disoproxil fumarate (TDF) with the purpose of enhancing its oral absorption.

Significance: TDF is a prodrug that has limited intestinal absorption because of its susceptibility to gut wall esterases. Hence, design of chitosan based polymeric novel nanocarrier systems can protect TDF from getting metabolized and also enhance the oral absorption.

Methods: The nanoparticles were prepared using the ionic gelation technique. The factors impacting the particle size and entrapment efficiency of the nanoparticles were evaluated using design of experiments approach. The optimized nanoparticles were characterized and evaluated for their ability to protect TDF from esterase metabolism. The nanoparticles were then studied for the involvement of active transport in their uptake during the oral absorption process. Further, in vivo pharmacokinetic studies were carried out for the designed nanoparticles.

Results: The application of design of experiments in the optimization process was useful to determine the critical parameters and evaluate their interaction effects. The optimized nanoparticles had a particle size of 156?±?5?nm with an entrapment efficiency of 48.2?±?1%. The nanoparticles were well characterized and provided metabolic protection for TDF in the presence of intestinal esterases. The nanoparticles were able to increase the AUC of tenofovir by 380%. The active uptake mechanisms mainly involving clathrin-mediated uptake played a key role in increasing the oral absorption of tenofovir.

Conclusions: These results show the ability of the designed chitosan based nanoparticles in enhancing the oral absorption of TDF along the oral route by utilizing the active endocytic uptake pathways.     

7-Ethyl-10-hydroxycamptothecin proliposomes with a novel preparation method: optimized formulation,characterization and in-vivo evaluation

Context:?The proliposomes were used to solve the stability of the ordinary liposomes. Objective: 7-ethyl-10-hydroxycamptothecin (SN-38) proliposomes for intravenous (i.v.) administration were prepared successfully by a new method.

Materials and methods:?SN-38 liposomes solution was reconstituting automatically from proliposomes on contact with the acetic acid buffer solution (0.2 M, pH 2.6). The formulation was optimized by the Box–Behnken design. The physicochemical characteristics of the SN-38 proliposomes were studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The stability studies were also carried on. The FLU–HPLC system was served to study the concentration of SN-38 in the plasma of Sprague Dawley (SD) rats.

Results:?The optimized formulation was SN-38: 0.03 g; Soybean phospholipid (SP): 0.6 g; dextrose: 3.00 g. The entrapment efficiency of the optimized formulation was >85% and the mean particle size was about 231 nm. The stability studies showed that SN-38 proliposomes were stable in dark at 20–25°C for 6 months at least. The pharmacokinetic parameters of i.v. administration demonstrated that the half-life of SN-38 loaded in the liposomes was prolonged in vivo.

Discussion and conclusion:?The SN-38 proliposomes was prepared successful by the analysis of TEM, SEM, DSC and XRD, and SN-38 liposomes could be reconstituted on contact with the hydration medium. SN-38 liposomes circulated for a longer time in the blood circulating system than SN-38 solution, which contributed to maintaining the drug action.     

Capsaicin pretreatment enhanced the bioavailability of fexofenadine in rats by P-glycoprotein modulation: in vitro,in situ and in vivo evaluation

Background and objective: Capsaicin is the main pungent principle present in chili peppers has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro, which may have the potential to modulate bioavailability of P-gp substrates. Therefore, purpose of this study was to evaluate the effect of capsaicin on intestinal absorption and bioavailability of fexofenadine, a P-gp substrate in rats.

Methods: The mechanistic evaluation was determined by non-everted sac and intestinal perfusion studies to explore the intestinal absorption of fexofenadine. These results were confirmed by an in vivo pharmacokinetic study of oral administered fexofenadine in rats.

Results: The intestinal transport and apparent permeability (P_app) of fexofenadine were increased significantly by 2.8 and 2.6 fold, respectively, in ileum of capsaicin treated rats when compared to control group. Similarly, absorption rate constant (K_a), fraction absorbed (F_ab) and effective permeability (P_eff) of fexofenadine were increased significantly by 2.8, 2.9 and 3.4 fold, respectively, in ileum of rats pretreated with capsaicin when compared to control group. In addition, maximum plasma concentration (C_max) and area under the concentration-time curve (AUC) were increased significantly by 2.3 and 2.4 fold, respectively, in rats pretreated with capsaicin as compared to control group. Furthermore, obtained results in rats pretreated with capsaicin were comparable to verapamil (positive control) treated rats.

Conclusions: Capsaicin pretreatment significantly enhanced the intestinal absorption and bioavailability of fexofenadine in rats likely by inhibition of P-gp mediated cellular efflux, suggesting that the combined use of capsaicin with P-gp substrates may require close monitoring for potential drug interactions.     

Improved oral bioavailability and therapeutic efficacy of dabigatran etexilate via Soluplus-TPGS binary mixed micelles system

The clinical use of dabigatran etexilate (DABE) is limited by its poor absorption and relatively low bioavailability. Our study aimed to explore the potential of a mixed micelle system composed of Soluplus^® and D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) to improve the oral absorption and bioavailability of DBAE. DBAE was first encapsulated into Soluplus/TPGS mixed micelles by a simple thin film hydration method. The DBAE loaded micelles displayed an average size distribution of around 83.13?nm. The cellular uptake of DBAE loaded micelles in Caco-2 cell monolayer was significantly enhanced by 2–2.6 fold over time as compared with DBAE suspension. Both lipid raft/caveolae and macropinocytosis-mediated the cell uptake of DBAE loaded micelles through P-glycoprotein (P-gp)-independent pathway. Compared with the DBAE suspension, the intestinal absorption of DBAE from DBAE mixed micelles in rats was significantly improved by 8 and 5-fold in ileum at 2?h and 4?h, respectively. Moreover, DBAE mixed micelles were absorbed into systemic circulation via both portal vein and lymphatic pathway. The oral bioavailability of DBAE mixed micelles in rats was 3.37 fold higher than that of DBAE suspension. DBAE mixed micelles exhibited a comparable anti-thrombolytic activity with a thrombosis inhibition rate of 63.18% compared with DBAE suspension in vivo. Thus, our study provides a promising drug delivery system to enhance the oral bioavailability and therapeutic efficacy of DBAE.     

Chitosan microparticles: influence of the gelation process on the release profile and oral bioavailability of albendazole,a class II compound

Encapsulation of albendazole, a class II compound, into polymeric microparticles based on chitosan-sodium lauryl sulfate was investigated as a strategy to improve drug dissolution and oral bioavailability. The microparticles were prepared by spray drying technique and further characterized by means of X-ray powder diffractometry, infrared spectroscopy and scanning electron microscopy. The formation of a novel polymeric structure between chitosan and sodium lauryl sulfate, after the internal or external gelation process, was observed by infrared spectroscopy. The efficiency of encapsulation was found to be between 60 and 85% depending on the internal or external gelation process. Almost spherically spray dried microparticles were observed using scanning electron microscopy. In vitro dissolution results indicated that the microparticles prepared by internal gelation released 8% of the drug within 30?min, while the microparticles prepared by external gelation released 67% within 30?min. It was observed that the AUC and C_max values of ABZ from microparticles were greatly improved, in comparison with the non-encapsulated drug. In conclusion, the release properties and oral bioavailability of albendazole were greatly improved by using spraydried chitosan-sodium lauryl sulphate microparticles.