Properties of theophylline tablets dry powder coated with Eudragit® E PO and Eudragit® L 100-55

The aim of the present study was to investigate the influence of Eudragit^® E PO on the drug release mechanism of Eudragit^® L 100-55 film coatings applied to theophylline tablets by a dry powder coating technique. The process was entirely liquid-free. Calculation of the Flory-Huggins interaction parameter based on solubility parameters suggested immiscibility of the two copolymers. MDSC thermograms were characterized by two glass transitions for the investigated Eudragit^® E PO/Eudragit^® L 100-55 ratios and confirmed incomplete miscibility of the copolymers at processing conditions. FT-IR analysis was employed to study binding interactions of the polymers. Due to the higher affinity of the plasticizer, triethyl citrate, for Eudragit^® E PO compared to Eudragit^® L 100-55, redistribution of the plasticizer was observed during the curing phase of the process. Plasticizer migration also affected the initial phase of drug release from powder-coated theophylline tablets that were stored for four weeks. Drug release from powder-coated tablets was dependent on the polymer blend ratio, coating thickness, and the pH of the dissolution medium. A broad range of pH dependent theophylline release profiles were obtained as a function of the polymer blend ratio. The particle size of the coating powder influenced the microstructure of the film coating.     

Pectin-coated chitosan–LDH bionanocomposite beads as potential systems for colon-targeted drug delivery

This work introduces results on a new drug delivery system (DDS) based on the use of chitosan/layered double hydroxide (LDH) biohybrid beads coated with pectin for controlled release in the treatment of colon diseases. Thus, the 5-aminosalicylic acid (5ASA), the most used non-steroid-anti-inflammatory drug (NSAID) in the treatment of ulcerative colitis and Crohn's disease, was chosen as model drug aiming to a controlled and selective delivery in the colon. The pure 5ASA drug and the hybrid material prepared by intercalation in a layered double hydroxide of Mg₂Al using the co-precipitation method, were incorporated in a chitosan matrix in order to profit from its mucoadhesiveness. These compounds processed as beads were further treated with the polysaccharide pectin to create a protective coating that ensures the stability of both chitosan and layered double hydroxide at the acid pH of the gastric fluid. The resulting composite beads presenting the pectin coating are stable to water swelling and procure a controlled release of the drug along their passage through the simulated gastrointestinal tract in in vitro experiments, due to their resistance to pH changes. Based on these results, the pectin@chitosan/LDH-5ASA bionanocomposite beads could be proposed as promising candidates for the colon-targeted delivery of 5ASA, with the aim of acting only in the focus of the disease and minimizing side effects.     

Synthesis and characterization of a new carrier based on Eudragit® EPO/S100 interpolyelectrolyte complex for controlled colon-specific drug delivery

With a view to the development of peroral controlled drug delivery systems, a new interpolyelectrolyte complex (IPEC) between oppositely charged types of Eudragit?, EPO and S100, has been synthesized and investigated at neutral pH values. According to data of turbidimetry, capillary viscometry, gravimetry, and elemental analysis, the obtained IPEC has a composition of Z = [EPO]/[S100] = 1.26. Structural features of the IPEC samples have been evaluated by FTIR spectroscopy and modulated-temperature differential scanning calorimetry. The results confirmed that the IPEC is stabilized by cooperative intermacromolecular ionic bonds, is chemically homogeneous, and is characterized by a single glass transition temperature. The observed features of the carrier swelling and diclofenac sodium release from the matrix system confirm that the proposed IPEC has great potential to be used as a carrier for controlled colon-specific drug delivery.     

Fabrication and evaluation of Eudragit® polymeric films for transdermal delivery of piroxicam

The aims of this work were to develop and characterize the prolonged release piroxicam transdermal patch as a prototype to substitute oral formulations, to reduce side effects and improve patient compliance. The patches were composed of film formers (Eudragit^®) as a matrix backbone, with PVC as a backing membrane and PEG200 used as a plasticizer. Results from X-ray diffraction patterns and Fourier transform-infrared spectroscopy indicated that loading piroxicam into films changed the drug crystallinity from needle to an amorphous or dissolved form. Piroxicam films were prepared using Eudragit^® RL100 and Eudragit^® RS100 as film formers at various ratios from 1:0 to 1:3. Films prepared solely by Eudragit^® RL100 showed the toughest and softest film, while other formulations containing Eudragit^® RS100 were hard and brittle. Drug release kinetic data from the films fitted with the Higuchi model, and the piroxicam release mechanism was diffusion controlled. Among all formulation tested, Eudragit^® RL100 films showed the highest drug release rate and the highest drug permeation flux across human epidermal membrane. Increasing drug loading led to an increase in drug release rate. Eudragit^® can be used as a film former for the fabrication of piroxicam films.     

Thermosensitive PEG–PCL–PEG (PECE) hydrogel as an in situ gelling system for ocular drug delivery of diclofenac sodium

Development of efficient ocular drug delivery systems was still a challenging task. The objective of this article was to develop a thermosensitive PEG–PCL–PEG (PECE) hydrogel and investigate its potential application for ocular drug delivery of diclofenac sodium (DIC). PECE block polymers were synthesized by coupling MPEG-PCL co-polymer using IPDI reagent, and then its sol–gel transition as a function with temperature was investigated by a rheometer. The results showed that 30% (w/v) PECE aqueous solution exhibited sol–gel transition at approximately 35?°C. In vitro release profiles showed the entrapped DIC was sustained release from PECE hydrogels up to 7 days and the initial drug loading greatly effect on release behavior of DIC from PECE hydrogels. MTT assay results indicated that no matter PECE or 0.1% (w/v) DIC-loaded PECE hydrogels were nontoxic to HCEC and L929 cells after 24?h culturing. In vivo eye irritation test showed that the instillation of either 30% (w/v) PECE hydrogels or 0.1% (w/v) DIC-loaded PECE hydrogels to rabbit eye did not result in eye irritation within 72?h. In vivo results showed that the AUC_0–48?h of 0.1% (w/v) DIC-loaded PECE hydrogels exhibited 1.6-fold increment as compared with that of commercial 0.1% (w/v) DIC eye drops, suggesting the better ophthalmic bioavailability could be obtained by the instillation of 0.1% (w/v) DIC-loaded PECE hydrogels.     

Novel microparticle drug delivery systems based on chitosan and Eudragit®RSPM to enhance diltiazem hydrochloride release property

The aim of this study was to enhance the release properties of diltiazem hydrochloride (diltiazem HCl) by using microparticle system. For this reason, microparticle drug delivery systems based on chitosan and Eudragit^®RSPM were developed. The microparticles were prepared by using double-emulsion solvent extraction method and the mean sizes of microparticles were less than 120?µm. The in vitro drug release from microparticles was studied in simulated gastric (pH 1.2) and intestinal media (pH 7.4) than the results were evaluated by kinetically. In vitro diltiazem HCl release from microparticles showed good zero order kinetic. For the microparticles with chitosan, the release of diltiazem HCl at pH 1.2 could be effectively sustained, while the release of diltiazem HCl increased at pH 7.4 when compared to Eudragit^®RSPM microparticles. The highest release percent obtained was 1:1 ratio of drug: polymer at pH 1.2 and 7.4. All results clearly suggest that the release properties of diltiazem HCl were improved by using microparticle systems especially which contain chitosan.     

Eudragit® S100 coated calcium pectinate microspheres of curcumin for colon targeting

Currently, colon-specific drug delivery systems have been investigated for drugs that can exert their bioactivities in the colon. In this study, Eudragit? S100 coated calcium pectinate microsphere, a pH-dependent and enzyme-dependent system, as colon-specific delivery carrier for curcumin was investigated. Curcumin-loaded calcium pectinate microspheres were prepared by emulsification-linkage method, and the preparation technology was optimised by uniform experimental design. The morphology of microspheres was observed under scanning electron microscopy. Interactions between drug and polymers were investigated with differential scanning calorimetry (DSC) and X-ray diffraction. In?vitro drug release studies were performed in simulated colonic fluid in the presence of Pectinex Ultra SP-L or 1% (w/v) rat caecal content, and the results indicated that the release of curcumin was significantly increased in the presence of 1% (w/v) rat caecal contents. It could be concluded that Eudragit? S100 coated calcium pectinate microsphere was a potential carrier for colon delivery of curcumin.     

Solid lipid nanoparticles for transdermal delivery of diclofenac sodium: preparation, characterization and in vitro studies

The aim of this study was to prepare diclofenac sodium (DNa) solid lipid nanoparticles (SLNs) by a modified emulsion/solvent evaporation method for transdermal delivery. Five independent processing parameters including the lipid matrix, emulsifiers, co-emulsifiers, water-dispersed phase and organic phase were assessed systematically to enhance the entrapment of DNa. The SLNs produced by optimal formulation were submicrometre size with low polydispersity index, the entrapment efficiency was about 89% and the drug loading was about 9.5%. Shape and surface morphology were determined by transmission electron microscopy, which revealed the fairly spherical and core-shell shapes of the SLNs. The in?vitro release of SLNs showed a two-step release pattern: one initial burst release followed by a second slow-release phase. In the in?vitro cutaneous permeation studies, value of flux obtained for DNa solution was higher than that of SLNs suspension. SLNs had also been shown to improve the dermal localization of DNa.     

Development of solid nanoparticles based on hydroxypropyl-β-cyclodextrin aimed for the colonic transmucosal delivery of diclofenac sodium

Objectives Nanoparticles were designed for the oral administration and transmucosal colon delivery of drugs. Methods Preparation parameters were studied in order to develop solid pH‐dependent drug‐release nanoparticles, constituted by hydroxypropyl‐β‐cyclodextrin and/or Eudragit^® L100 loaded with diclofenac sodium. Nanoemulsions were prepared by the emulsion‐evaporation method using various homogenizers. Different preparative conditions were tested. The emulsions obtained were analysed in terms of size and then dried to obtain solid nanoparticles which were characterized in vitro (particle size, morphology, dissolution, solid state characterization). The effect of nanoparticles on drug permeation through synthetic membranes, colonic pig mucosa and Caco2 cell line were performed. Toxicity studies were carried out to assess the safety of the raw materials used and the nanosystems produced. Key findings Appropriate parameters to obtain nanoemulsions stable enough to be desiccated were determined: Panda NS100L was the most suitable homogenizer for the preparation; particle size ranged between 100 and 600 nm depending on the production method. Solid nanoparticles were obtained by an exsiccation process, which does not modify the mean size. pH‐dependent drug‐release nanoparticles were obtained. The nanoencapsulation process decreased the crystallinity of the drug. Materials and nanoparticles were highly biocompatible. Transmucosal delivery of drug is dependent on the polymer and the test employed: cyclodextrin improved drug permeation across colonic pig mucosa. Conclusions Formulations containing hydroxypropyl‐β‐cyclodextrin represent new colon‐targeted nanoparticles for transmucosal delivery of drugs.     

A pH/enzyme-responsive polymer film consisting of Eudragit® FS 30 D and arabinoxylane as a potential material formulation for colon-specific drug delivery system

Polymer film based on pH-dependent Eudragit^® FS 30 D acrylic polymer in association with arabinoxylane, a polysaccharide issued from gum psyllium, was produced by way of solvent casting. Physical-chemical characterization of the polymer film samples was performed by means of thermogravimetry (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Furthermore, water-equilibrium swelling index (I_s) and weight loss of the films in KCl buffer solution of pH 1.2, in KH₂PO₄ buffer solution of pH 5.0, or in KH₂PO₄ buffer solution of pH 5.0 consisting of 4% enzyme Pectinex^® 3X-L (w/v) were also carried out for the film characterization. No chemical interactions between the Eudragit^® FS 30 D and the arabinoxylane polymer chains were evidenced, thus suggesting that the film-forming polymer structure was obtained from a physical mixture of both polymers. The arabinoxylane-loader films showed a more pronounced weight loss after their immersion in buffer solution containing enzyme Pectinex^® 3X-L. The introduction of the arabinoxylane makes the film more susceptible to undergo an enzymatic degradation. This meant that the enzyme-dependent propriety issued from the arabinoxylane has been imprinted into the film formulation. This type of polymer film is an interesting system for applications in colon-specific drug delivery system.     

Interaction between Eudragit® E100 and anionic drugs: addition of anionic polyelectrolytes and their influence on drug release performance

In this work, we report results concerning the study of solid complexes compounded by a cationic polymethacrylate (Eudragit® E100, Eu) and mesalazine (M) (Eu–M_x complex). The influence of an anionic polyacrylic acid polymer (carbomer, C) on dissolution behavior of M from the complex was evaluated (Eu–M_xC_y complex). The dissolution profiles and solvent front movements of solid matrices in different media (water, buffer pH 7.4, 0.9% NaCl) were investigated and ionic interactions among Eu, M, and C were determined through Fourier transform infrared (FT‐IR) spectroscopy. For Eu–M_x complexes, the affinity between M and Eu modulated the delivery of free M in solution, with the dissolution media affecting the delivery rate mainly due to an ionic interchange process between M and anionic electrolytes (i.e., Cl^?). FTIR spectroscopy allowed the ionic interaction between Eu and M to be verified. The addition of C (Eu–M_xC_y) influenced the dissolution behavior of these matrices. As the amount of C was increased, the release mechanism changed from diffusion (Eu–M₅₀) or anomalous (Eu–M₁₀₀) to zero order (Eu–M_xC₅₀). This variation in rate delivery was also affected by the dissolution media, as occurred with Eu–M_x complexes. The formation of the gel layer during the dissolution process, as consequence of Eu–M_xC_y matrices hydration, was influenced by C amount and dissolution media. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4664–4673, 2011     

Novel interpenetrating network microspheres of xanthan gum–poly(vinyl alcohol) for the delivery of diclofenac sodium to the intestine—in vitro and in vivo evaluation

Xanthan gum (XG), a trisaccharide branched polymer and poly vinyl alcohol (PVA), was used to develop pH-sensitive interpenetrating network (IPN) microspheres by emulsion cross-linking method in the presence of glutaraldehyde as a cross-linker to deliver model anti-inflammatory drug, diclofenac sodium (DS) to the intestine. Various formulations were prepared by changing the ratio of XG:PVA, extent of cross-linking in order to optimize the formulation variables on drug encapsulation efficiency, and release rate. Formation of interpenetrating network and the chemical stability of DS after penetration of microspheres was confirmed by Fourier Transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis were done on the drug loaded microspheres which confirmed molecular dispersion of DS in the IPN. Microspheres formed were spherical with smooth surfaces, as evidenced by scanning electron microscopy (SEM), and mean particle size, as measured by laser light scattering technique ranged between 310.25–477.10 µm. Drug encapsulation of up to 82.94% was achieved as measured by UV method. Both equilibrium and dynamic swelling studies and in vitro release studies were performed in pH 1.2 and 6.8. Release data indicated a Fickian trend of drug release which depends on the extent of cross-linking and the ratio of XG:PVA present in the microsphere. When subjected to in vivo pharmacokinetic evaluation in rabbits, microparticles show slow and prolonged drug release when compared with DS solution. Based on the results of in vitro and in vivo studies it was concluded that these IPN microspheres provided oral controlled release of water-soluble DS.     

α-常春藤皂苷丙烯酸树脂L100-55纳米粒的制备及体外评价

目的：采用肠溶材料丙烯酸树脂L100-55作为载体材料,制备α-常春藤皂苷丙烯酸树脂纳米粒（ SPD-L100-55-NPs）并进行体外评价。方法采用改良乳化溶剂扩散法制备SPD-L100-55-NPs,以粒径、包封率（ EE）和多分散指数（ P. I.）为综合指标,通过单因素实验和正交设计实验优化纳米粒的处方工艺,以红外光谱（ FT-IR）、X射线衍射（ XRD）、差示扫描量热分析（ DSC）等对制备的纳米粒进行评价,并考察其体外释放特性。结果制得的SPD-L100-55-NPs纳米粒外观圆整、分布均匀,平均粒径为（63.5±3.6）nm,包封率为98.91%±0.18%,P. I.为0.198±0.014。药物在纳米粒中被载体材料有效包裹,体外释放具有缓释特性和PH依赖性。结论所制得的纳米粒圆整均匀、包封率高,在体外具有良好的缓释特性和PH敏感性。     

A medusa-like β-cyclodextrin with 1-methyl-2-(2′-carboxyethyl) maleic anhydrides,a potential carrier for pH-sensitive drug delivery

Abstract

We developed a new pH-sensitive drug delivery carrier based on β-cyclodextrin (β-CD) and 1-methyl-2-(2′-carboxyethyl) maleic anhydrides (MCM). The primary hydroxyl groups of β-CD were successfully attached to MCM residues to produce a medusa-like β-CD–MCM. The MCM residue was conjugated with cephradine (CP) with high efficiency (?>?90%). More importantly, β-CD–MCM–CP responded to the small pH drop from 7.4 to 5.5 and released greater than 80% of the drugs within 0.5?h at pH 5.5. In addition, the inclusion complex between β-CD–MCM–CP and the adamantane derivative was formed by simple mixing to show the possibility of introducing multi-functionality. Based on these results, β-CD–MCM can target weakly acidic tissues or organelles, such as tumours, inflammatory tissues, abscesses or endosomes, and be easily modified with various functional moieties, such as ligands for cell binding or penetration, enabling more efficient and specific drug delivery.