Fabrication of novel GMO/Eudragit E100 nanostructures for enhancing oral bioavailability of carvedilol

In the present work, novel nanostructures comprising of glyceryl monooleate (GMO) and Eudragit E100 were prepared using high intensity ultrasonic homogenization. 3² Factorial design approach was used for optimization of nanostructures. Results of regression analysis revealed that the amount of GMO and Eudragit E100 had a drastic effect on particle size and percent entrapment efficiency. Optimized carvedilol-loaded nanostructures (Car-NS) were characterized by FTIR, TEM, DSC, in vitro drug release study. Pharmacokinetic parameters such as C_max, T_max, Ke, Ka, V_d and AUC were estimated for Car-NS upon its oral administration in Sprague-Dawley rats. Particle size of Car-NS was found to be 183?±?2.43?nm with an entrapment efficiency of 81.4?±?0.512%. FTIR studies revealed loading and chemical compatibility of carvedilol with the components of nanostructures. DSC thermograms did not show endothermic peak for melting of carvedilol which could be attributed to solubilization of carvedilol in molten GMO during DSC run. The prepared Car-NS released carvedilol in sustained manner over a period of 10 h as suggested by in vitro drug release study. The pharmacokinetic study of Car-NS showed significant improvement in C_max (two fold, p?p?Eudragit E100 nanostructures having ability to release the drug in sustained manner with enhanced oral bioavailability can prove to be a promising carrier system for poorly water soluble drugs.     

Formulation of Insulin-Loaded Polymeric Nanoparticles Using Response Surface Methodology

The objective of this work was to formulate new oral insulin-loaded nanoparticules using the response surface methodology. The insulin nanoparticles were prepared by a water-in-oil-in-water emulsification and evaporation method. The polymers used for the encapsulation were blends of biodegradable poly-epsilon-caprolactone (PCL) and of positively-charged, nonbiodegradable polymer (Eudragis RS®). A central composite design has been built to investigate the effects of three controlled variables: ratio of polymers (PCL/RS ratio), volume, and pH of the aqueous solution of polyvinyl alcohol. The nanoparticles were characterized by measuring the amount of entrapped insulin, the particle size, the polydispersity of the obtained particles, the zeta potential, and the amount of insulin released after 7 hours. A second-order model was evaluated by multiple regression and was statistically tested for each of the studied controlled variable. The obtained polynomials proved efficient to localize an optimal operating area highlighted by the use of three-dimensional response surfaces and their corresponding isoresponse curves. An interesting formulation given by the models was selected, prepared, and evaluated. The corresponding quantity of entrapped insulin was 25 IU per 100 mg of polymer, and the particle size was 350 nm with a polydispersity of 0.21. The quantity of released insulin was 4.8 IU per 100 mg of polymer after 7 hours and the zeta potential was + 44 mV. All these collected values were in perfect accordance with values estimated by the models. Finally, the results suggested that PCL/RS 50/50 nanoparticles might represent a promising formulation for oral delivery of insulin.     

Nanosponge-based pediatric-controlled release dry suspension of Gabapentin for reconstitution

Abstract

Context: Gabapentin was selected to formulate oral controlled release dry suspension because of short biological half life of 5–7?h and low bioavailability (60%). Gabapentin is a bitter drug so an attempt was made to mask its taste.

Objective: To formulate and evaluate controlled release dry suspension for reconstitution to increase the bioavailability and to control bitter taste of drug.

Materials and methods: Cyclodextrin based nanosponges were synthesized by previously reported melt method. The nanosponge–drug complexes were characterized by FTIR, DSC and PXRD as well as evaluated for taste and saturation solubility. The complexes were coated on Espheres by a suspension layering technique followed by coating with ethyl cellulose and Eudragit RS-100. A dry powder suspension for reconstitution of the microspheres was formulated and evaluated for taste, redispersibility, in vitro dissolution, sedimentation volume, leaching and pharmacokinetics.

Results and discussion: The complexes showed partial entrapment of drug nanocavities. Significant decrease in solubility (25%) was observed in the complexes than pure drug in different media. The microspheres of nanosponge complexes showed desired controlled release profile for 12?h. Insignificant drug leaching was observed in reconstituted suspension during storage for 7 days at 45?°C/75% RH. Nanosponges effectively masked the taste of Gabapentin and the coating polymers provided controlled release of the drug and enhanced taste masking. The results of in vivo studies showed increase in bioavailability of controlled release suspension by 24.09% as compared to pure drug.

Conclusion: The dry powder suspension loaded with microspheres of nanosponges complexes can be proposed as a suitable controlled release drug delivery for Gabapentin.     

Development of mefenamic acid–loaded polymeric microparticles using solvent evaporation and spray-drying technique

Ethyl cellulose (EC) and Eudragit RL-100 (ERL-100) were used for the preparation of sustained released microparticles of mefenamic acid (MFN) by using oil-in-oil (o/o) solvent evaporation as well as spray drying. A Plackett-Burman design was employed using Design-Expert software. The resultant microparticles were characterized for their size, surface morphology, encapsulation efficiency, and drug release. Imaging of microparticles was performed by field emission scanning electron microscopy. The drug and polymer interaction was investigated by Fourier transform infrared (FTIR) spectroscopy and X-ray powder diffractometry (XRPD). The microparticles showed encapsulation efficiency in the range of 29.44 to 89.20% by solvent evaporation and 83.73 to 96.69% by spray drying. The surface of the microparticles was smooth, round, and regular, without any erosion and cracking. The size of the microparticles was found to be in the range of 6.55 to 41.1 µm. FTIR analysis confirmed no interaction of MFN with the polymers. XRPD showed the dispersion of the drug within the microparticle formulation. These results helped in finding the optimum formulation variables for encapsulation efficiency (EE) of microparticles.     

Eudragit L-100固定球毛壳霉菌木聚糖酶酶学性质的研究

采用可逆溶解性聚合物EudragitL-100对球毛壳菌木聚糖酶进行了吸附固定化。在1.0%EudragitL-100浓度时获得10.6IU/mg载体的固定化酶活和88.47%的酶活回收。酶固定化后最适温度不变,最适pH向碱性方向移动了一个pH单位。固定化酶热稳定性和操作稳定性显著提高,循环利用6次仍保留65%初始酶活。木聚糖水解产物测定表明,在同酶用量的条件下固定化后总还原糖产量明显高于游离酶,二者水解产物均以低聚糖为主,酶固定化后水解产物木二糖含量显著高于游离酶,成为主要的产物。木聚糖酶固定化后各方面特性明显优于游离酶,在低聚糖生产中有实际应用价值。     

Characterization of the mechanism of interaction in ibuprofen-Eudragit RL100 coevaporates

The present study is a preliminary exploration of the affinity between a carboxylic model drug, the nonsteroidal antiinflammatory agent ibuprofen (IBU) and Eudragit RL100 (RL) polymer. Due to the presence of a variable amount of quaternary ammonium groups in this matrix, physical and chemical interaction with the carboxylic drug can occur, which reinforces its scant mechanical dispersion in the polymer network and can ultimately affect its release profile in vitro and in vivo. To study these aspects, IBU was mixed at increasing weight ratios and in different chemical forms (free acid, sodium salt, and n-butyl ester), to investigate further the role of the carboxylic group in the interaction with the RL polymer. Therefore, IBU-RL solid dispersions (coevaporates) were obtained and fully characterized in the solid state through spectroscopic, calorimetric, and x-ray diffractometric analyses. The in vitro release pattern of the drug, in the different chemical states, was studied for the coevaporates, compared with drug-RL physical mixtures, along with drug adsorption profiles from aqueous solutions on the surface of the polymer granules.     

Stabilization and Target Delivery of Nattokinase Using Compression Coating

ABSTRACT

The aim of the work is to develop a new formulation in order to stabilize a nutraceutical enzyme Nattokinase (NKCP) in powders and to control its release rate when it passes through the gastrointestinal tract of human. NKCP powders were first compacted into a tablet, which was then coated with a mixture of an enteric material Eudragit® L100-55 (EL100-55) and Hydroxypropylcellulose (HPC) by direct compression. The activity of the enzyme was determined using amidolytic assay and its release rates in artificial gastric juice and an intestinal fluid were quantified using bicinchoninic acid assay. Results have shown that the activity of NKCP was pressure independent and the coated tablets protected NKCP from being denatured in the gastric juice, and realized its controlled release to the intestine based on in vitro experiments.     

Spray-dried pH-sensitive microparticles: effectual methodology to ameliorate the bioavailability of acid labile pravastatin

Pravastatin is a promising drug utilized in the treatment of hyperlipidemia, yet, its main clinical limitation is due to gastric liability which fractions its oral bioavailability to less than 18%. The purpose of the current study is to encapsulate pravastatin into Eudragit^®-based spray-dried microparticles aspiring to overcome its acid liability. With the aim to optimize the microparticles, formulation and process parameters were studied through acid resistance challenging test. Physicochemical characterization of the optimized spray-dried pH-sensitive microparticles namely; in-vitro dissolution, surface morphology, compatibility, and solid-state studies were performed. Moreover, in-vivo evaluation of the microparticles and accelerated stability studies were carried out. The results outlined that polymer to drug ratio at 5:1 and pravastatin concentration at 1%w/w in spray-drying feed solution showed 38.55% and 53.97% encapsulation efficiency, respectively. The significance of process parameters specifically; the flow rate and the inlet temperature on microparticles surface integrity were observed, and optimized until encapsulating efficiency reached 72.37%. The scanning electron microscopical examination of the optimized microparticles illustrate uniform smooth surface spheres entrapping the drug in an amorphous state as proved through Differential Scanning Calorimetry (DSC) and Fourier Transfer Infrared (FTIR) studies. The in-vivo evaluation demonstrated a 5-fold enhancement in pravastatin bioavailability compared to the marketed product. The results provided evidence for the significance of spray-dried pH-sensitive microparticles as a promising carrier for pravastatin, decreasing its acid liability, and improving its bioavailability.     

Development of a topical mupirocin spray for antibacterial and wound-healing applications

Objective: The aim of this study was to develop mupirocin topical spray using Eudragit E100 as a film-forming agent for the treatment of bacterial skin infections as well as to promote wound healing.

Materials and methods: Twenty-seven of mupirocin formulations were formulated containing Eudragit E100 and other excipients. Mupirocin spray was prepared by aerosol crimping and filling machine using HFA-134a as a propellant. The formulations were evaluated for their stability and physicochemical properties. The factorial study was applied to evaluate the effects of glycerol and PEG400 on mupirocin-loaded Eudragit E100 films. The optimized formulation was assessed of drug release, antibacterial activities and in vitro cell line studies in comparison to the ointment formulation.

Results and discussion: Mupirocin sprays were formulated and optimized to obtain the formulation with excellent physicochemical and mechanical properties of the dressing film. The formulation had an excellent stability up to a year with more than 80% of mupirocin content. Mupirocin was released from the film up to 90% within 2?h. The formulation had a potent antibacterial effect against S. aureus and S. epidermidis. The formulation was safe to use as a topical formulation that had no toxicity to keratinocytes, fibroblasts and monocytes. The formulation also had an antiendotoxin effect without stimulating the production of NO and inflammatory cytokines (IL-1β and TNF-α).

Conclusions: Mupirocin topical spray was successful developed as a topical formulation and can be used instead of the ointment formulation. Animal experiments are warranted to further emphasize the safe use in the human skin.     

Microscopic Fourier transform infrared/differential scanning calorimetry system used to study the different thermal behaviors of polymethacrylate copolymers of eudragits RS,RL, E 30D,or E

The thermal stability of Eudragits RL, RS, E 30D, and E films was qualitatively investigated by the reflectance Fourier transform infrared microspectroscopy equipped with differential scanning calorimetry (FTIR/DSC microscopic system). DSC and thermogravimetric analysis (TGA) were also used to study the thermal behavior of the granules of the raw material and the film of these polymers. The results indicate that the Eudragit RL, RS, or E 30D polymer exhibited a higher thermal‐stable behavior, but Eudragit E easily formed the six‐membered cyclic anhydride through heating process via the inter‐ or intramolecular ester condensation. The leaving group in Eudragit E molecule was larger than that in Eudragit E 30D, and the leaving group of salt in Eudragit RS or RL was too stable to polycondense. The DSC thermograms and TGA curve also confirmed this result. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 829–835, 2000