Melt Extrusion Method Research Articles

Design and development of intraocular polymeric implant systems for long-term controlled-release of clindamycin phosphate for toxoplasmic retinochoroiditis.

Background:The release of the anti-toxoplasmosis drug, clindamycin phosphate, from intraocular implants of the biodegradable polymers poly (D, L-lactic acid) (PLA) and poly (D, L-lactide-co-glycolide) (PLGA) has been studied in vitro.Materials and Methods:The preparation of the implants was performed by a melt-extrusion method. The developed extrudates were characterized and compared in in-vitro release profiles for elucidating the drug release mechanism. The formulations containing up to 40% w/w of drug were prepared. Release data in phosphate buffer (pH 7.4) were analyzed by high performance liquid chromatography. The release kinetics were fitted to the zero-order, Higuchi's square-root, first order and the Korsmeyer-Peppas empirical equations for the estimation of various parameters of the drug release curves. Degradation of implants was also investigated morphologically with time (Scanning Electron Microscopy).Results:It was observed that, the release profiles for the formulations exhibit a typical biphasic profile for bulk-eroding systems, characterized by a first phase of burst release (in first 24 hrs), followed by a phase of slower release. The duration of the secondary phase was found to be proportional to the molecular weight and monomer ratio of copolymers and also polymer-to-drug ratios. It was confirmed that Higuchi and first-order kinetics were the predominant release mechanisms than zero order kinetic. The Korsmeyer-Peppas exponent (n) ranged between 0.10 and 0.96. This value, confirmed fickian as the dominant mechanism for PLA formulations (n ≤ 0.45) and the anomalous mechanism, for PLGAs (0.45 < n < 0.90).Conclusion:The implant of PLA (I.V. 0.2) containing 20% w/w of clindamycin, was identified as the optimum formulation in providing continuous efficient in-vitro release of clindamycin for about 5 weeks.

Mechanical and Dielectric Behaviour of CaCu3Ti4O12 and Nb Doped CaCu3Ti4O12 Poly(vinylidene fluoride) Composites

PVDF has been reinforced with different amount of CaCu3Ti4-5x/4NbxO12 with x=0.05 powder prepared by solid state ceramic method. Composites were prepared by melt extrusion method. Phase composition was studied using powder X-ray diffraction (XRD). Microstructural, dielectric, and mechanical properties have also been studied. These composites have Young’s modulus more than that of pure PVDF. Two dielectric relaxations, one at low frequency and the other at high frequency, have been observed in these composites. Dielectric relaxation at low frequencies is of Maxwell-Wagner type while the one observed at high frequency is due to hopping of electrons among different valent states of transition metal ions. Nature of dielectric relaxation has been analysed using H-N function.

Design and characterisation of a polyethylene oxide matrix with the potential use as a teat insert for prevention/treatment of bovine mastitis.

This manuscript reports (for the first time) on antibiotic-free polymeric inserts for the prevention and/or treatment of bovine mastitis. Polyethylene oxide (PEO)-based inserts were prepared using different concentrations of various hydrophilic polymers and water-soluble and water-insoluble drug-release-modifying excipients. A simple and scalable melt-extrusion method was employed to prepare the inserts. The prepared inserts were characterised for their dimension, rheological and mechanical properties. The in vitro release of a model bacteriostatic drug (salicylic acid) from the prepared inserts was studied to demonstrate the effectiveness and reproducibility of the melt-extrusion manufacturing method. Further, the in vitro stability of the inserts was evaluated using gel permeation chromatography (GPC) to monitor any change in molecular weight under real-time and accelerated storage conditions. The investigated inserts were stable at accelerated storage conditions over a period of 6 months. PEO inserts have the potential to serve a dual purpose, act as a physical barrier against pathogens invading the teat canal of cows and possibly control the release of a drug.

Effects of dry method esterification of starch on the degradation characteristics of starch/polylactic acid composites

Maleic anhydride esterified corn starch was prepared by dry method. Esterified starch/polylactic acid (PLA) biodegradable composite was produced via melt extrusion method with blending maleic anhydride esterified corn starch and PLA. The influence of the dry method esterification of starch on the degradation characteristics of starch/PLA composites was investigated by the natural aging degradation which was soil burial method. Test results of mass loss rate showed that the first 30 days of degradation was mainly starch degradation, and the degradation rate of esterified starch/PLA (ES/PLA) was slower than that of native starch/PLA (NS/PLA). Therefore, the damage degree of ES/PLA on the surface and inside was smaller than that of NS/PLA, and the infrared absorption peak intensities of CO, CO and CH were stronger than that of NS/PLA. With the increasing time of soil burial degradation, the damage degree of NS/PLA and ES/PLA on the exterior and interior were gradually increased, whereas the infrared absorption peak intensities of CO, CO and CH were gradually decreased. The XRD diffraction peak intensity of PLA in composites showed an increased trend at first which was then followed by a decreased one along with the increasing time of soil burial degradation, indicating that the degradation of amorphous regions of PLA was earlier than its crystalline regions. When the soil burial time was the same, the diffraction peak intensity of PLA in ES/PLA was stronger than that of NS/PLA. If the degradation time was the same, T0, Ti and residual rate of thermal decomposition of NS/PLA were larger than those of ES/PLA. The tensile strength and bending strength of composites were decreased gradually with soil burial time increasing. Both the tensile strength and bending strength of ES/PLA were stronger than those of NS/PLA.

Influences of Annealing on the Perfluorosulfonate Ion-Exchanged Membranes Prepared by Melt Extrusion

Perfluorosulfonate ion-exchanged membranes (PFSIEMs) have been prepared by the melt-extrusion method. Subsequently, the effect of annealing on the properties of PFSIEMs was studied. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) analysis suggested that −SO3– groups could be brought to the membrane surface, presumably by side chain movement during the course of thermal annealing. In the presence of coexisting ion clusters and crystallization, area resistance increased with the rise of the treatment temperature. X-ray diffraction (XRD) analysis further showed that the annealing treatment should increase the crystallinity of membranes, markedly. The equivalent weight (EW) and water uptake were also employed to evaluate the effect of annealing on membranes. For membranes prepared by melt extrusion, abnormal fluctuations are solely evident in the thermogravimetric (TG) traces of annealed specimens. In addition, two glass transition temperatures, ca. 120 and ca. 250 °C, have been...

Development, characterizations and biocompatibility evaluations of intravitreal lipid implants.

The treatment of posterior eye diseases is always challenging mainly due to inaccessibility of the region. Many drugs are currently delivered by repeated intraocular injections. The purpose of this study was to investigate the potential applications of natural triglycerides as alternative carriers to synthetic polymers in terms of drug release profile and also biocompatibility for intraocular use. In vitro/in vivo evaluations of intravitreal implants fabricated from the physiological lipid, glyceride tripalmitate containing clindamycin phosphate as a model drug was performed. The micro-implants with average diameter of 0.4 mm were fabricated via a hot melt extrusion method. The extrudates were analyzed using scanning electron microscopy, differential scanning calorimetry, and in vitro drug dissolution studies. For biocompatibility, the implants were implanted into rabbit eyes. Clinical investigations including fundus observations, electroretinography as well as histological evaluations were performed. In vitro tests guaranteed usefulness of the production method for preparing the homogenous mixture of the drug and lipid without affecting thermal and crystalinity characteristics of the components. In vitro releases indicated a bi-phasic pattern for lower lipid ratios, which were completed by the end of day three. With higher lipid ratios, more controlled release profiles were achieved until about ten days for a lipid ratio of 95%. Clinical observations did not show any abnormalities up to two months after implantation into the rabbit eye. These results suggest that although the implant could not adequately retard release of the present drug model yet, due to good physical characteristics and in vivo biocompatibility, it can represent a suitable device for loading wide ranges of therapeutics in treatment of many kinds of retinochoroidal disorders.

The Structure and Properties of EPDM/PP/OMMT Nanocomposites by Melt Extrusion

The EPDM/PP/OMMT nanocomposites were prepared with three different types of OMMT by melt extrusion method. The microstructure and mechanical properties of the nanocomposites were investigated. The intercalated structures of the nanocomposites were confirmed by transmission electron microscopy (TEM). The mechanical results showed that the OMMT (FMR242#) has the best reinforcement. When the content of OMMT was lower than 4wt. %, the mechanical properties of the nanocomposites improved greatly with the increase of the OMMT content.

Tracking of the solubility enhancement and drug release stability of melt extrudates containing mebendazole

Solid dispersions of mebendazole were prepared in view of improving its extent and rate of dissolution. The solid dispersions were prepared by hot melt extrusion method using water soluble polymers and isomalt, polyethylene glycol and triethyl citrate as plasticizer. Solubility studies showed that solubility of solid dispersions, pure drug and physical mixtures were higher in acidic dissolution medium. FT-IR studies showed that the drug was compatible with polymers and the characteristic peak of mebendazole disappeared in the extruded samples. DSC studies in combination with X-ray diffraction were carried out for the solid state characterization samples after melt extrusion. The extent and rate of mebendazole release was dependent on the composition of extrudates. The drug release stability was also dependent on the composition of melt extrudates which was supramolecularly tracked by positron annihilation lifetime spectroscopy based on the free volume changes of samples as a function of storage.

SOLUBILITY IMPROVEMENT OF POORLY WATER SOLUBLE DRUG FENOFIBRATE BY SOLID DISPERSION IN POLYETHYLENE GLYCOL-HYDROXY PROPYLE METHYLE CELLULOSE MIXTURE

The objective of this study is to formulate solid dispersion of fenofibrate by hot melt extrusion method for improving aque ous solubility . Different formulation was prepared mixing mi crocrystalline drug, Poly Ethyle n e Glycol (PEG) and other excipient at specific ratio . The drug was dissolved in the melt of excipient at 65 - 70 o C, cooled below 4 0 o C, and grinded to prepare fine po wder. The sol id system was characterized by Differential Scanning C alorimetry (DSC), Scanning E lectron M icroscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR), the dispersion testing in the water and simulated gastric fluid. It was confirmed that there is no chemical interaction between drug and excipient . In - v itro release testing showed that 76.85 % of the drug dissolved in distilled water in 60 minutes . Almost 100 % of drug release was found within 20 minutes and 30 minutes in 2 % S odium Lauryl S ulfate and 1 % Tween - 80 simulated gastric fluid respectively for drug, PEG and HPMC ratio 1:7.5:2.5. Thus, the aqueous solubility of this poorly water - soluble drug was greatly enhanced by solid dispersion in a surface - active carrier.

Enhanced solubility and dissolution of simvastatin by HPMC-based solid dispersions prepared by hot melt extrusion and spray-drying method

The objective of this study was to use low viscosity grade hydroxypropyl methyl cellulose (Methocel® E3 LV and Methocel® E5 LV) to enhance the solubility and dissolution of poorly water soluble drug simvastatin (SIM). Two different technologies, hot melt extrusion and spray drying were employed. Characterization of hot melt extrudes and spray dried samples was done by Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction studies and scanning electron microscopy. The result of the study showed the conversion of crystalline form drug into amorphous form indicating increase in dissolution rate and solubility of SIM.

FORMULATION AND EVALUATION OF TASTE MASKED ORODISPERSIBLE TABLETS OF AMLODIPINE BESYLATE BY DIRECT COMPRESSION

The purpose of this investigation was undertaken to design a simple, rapid , cost effective and highly efficient process to fabricate intensely bitter taste of Amlodipine Besylate by complexing drug with Aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratios by Hot - Melt Extrusion method. Taste masked complex were an alyzed with FTIR, DSC and XRD. DCP were tested for Hardness, Thickness, Weight Variation, Drug Content, Water absorption and In vitro Dispersion Test in Simulated Salivary Fluid pH 6.8. Taste masked granules were directly compressed into tablets using Koll odion CL and Croscarmellose Sodium (Ac - Di - Sol) as superdisintegrants. Tablets of batch F 6 containing mannitol and 6% wt/wt of Kollodion CL showed faster disintegration with in 24 sec and drug release (t 90 , 180sec) at Phosphate Buffer pH 6.8. The observed p olymer interaction and reduced crystallinity may be reason for increased dissolution rate. Thus results conclusively demonstrate successful masking of taste, disintegration and dissolution of the formulated

Crystallization behavior of poly(lactide)/poly(β‐hydroxybutyrate)/talc composites

AbstractThe morphology and miscibility of commercial poly(lactide) (PLA)/poly(β‐hydroxybutyrate) (PHB, from 5 to 20 wt %) blends prepared by melt extrusion method, were investigated using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) observations. The results show that for all the studied blend contents, PLA/PHB blends are immiscible. The effects of PHB and talc on the nonisothermal cold crystallization kinetics of PLA were examined using a differential scanning calorimetry (DSC) at different heating rates. PHB acted as a nucleating agent on PLA and the addition of talc to the blend yielded further improvement, since significant increase in the enthalpy peak was observed for samples containing 10 wt % PHB and talc (from 0.5 to 5 phr). The crystallization kinetics were then examined using the Avrami–Jeziorny and Liu–Mo approach. The simultaneous presence of PHB and talc induced a decrease of the crystallization half time. The evolution of activation energies determined with Kissinger's equation suggests that blending with PHB and incorporating talc promote nonisothermal cold crystallization of PLA. The synergistic nucleating effect of PHB and talc was also observed on isothermal crystallization of PLA from the melt. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

Solvent-Free Melt Electrospinning for Preparation of Fast Dissolving Drug Delivery System and Comparison with Solvent-Based Electrospun and Melt Extruded Systems

The solvent-free melt electrospinning (MES) method was developed to prepare a drug delivery system with fast release of carvedilol (CAR), a drug with poor water solubility. To the authors knowledge, this is the first report for preparing drug-loaded melt electrospun fibers. Cationic methacrylate copolymer of Eudragit® E type was used as a fiber forming polymer matrix. For comparison, ethanol-based electrospinning and melt extrusion (EX) methods were used to produce samples that had the same composition as the melt electrospun system. According to the results of scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and Fourier transformed infrared spectrometry investigations, amorphous solid nanodispersions/solutions of CAR in Eudragit® E matrix were obtained in all cases with 20 m/m % drug content. In vitro drug release in acidic media from the extrudates was significantly faster (5 min) than that from crystalline CAR. Moreover, ultrafast drug release was achieved from the solvent-free melt and ethanol-based electrospun samples because of their huge surface area and the soluble polymer matrix in the acidic media. These results demonstrate that solvent-free MES is a promising, novel technique for the production of drug delivery systems with enhanced dissolution because it can combine the advantages of EX (e.g., solvent-free, continuous process, and effective amorphization) and solvent-based electrospinning (huge product surface area).

Osmotic Pellet System Comprising Osmotic Core and In-Process Amorphized Drug in Polymer–Surfactant Layer for Controlled Delivery of Poorly Water-Soluble Drug

The aim of the present investigation was to develop controlled porosity osmotic system for poorly water-soluble drug based on drug in polymer-surfactant layer technology. A poorly water-soluble drug, glipizide (GZ), was selected as the model drug. The technology involved core of the pellets containing osmotic agent coated with drug dispersed in polymer and surfactant layer, finally coated with release-retardant layer with pore former. The optimized drug-layer-coated pellets were evaluated for solubility of GZ at different pH conditions and characterized for amorphous nature of the drug by differential scanning calorimetry and X-ray powder diffractometry. The optimized release-retardant layer pellets were evaluated for in vitro drug release at different pH, hydrodynamic, and osmolality conditions. The optimized drug layer showed improvement in solubility (10 times in pH 1.2, 11 times in pH 4.5, and 21 times in pH 6.8), whereas pellets coated with cellulose acetate (15.0%, w/w, weight gain) with pore former triethyl citrate (10.0%, w/w, of polymer) demonstrated zero-order drug release for 24 h at different pH conditions; moreover, retardation of drug release was observed with increment of osmolality. This system could be a platform technology for controlled delivery of poorly water-soluble drugs.

Comparison of melt extrusion and thermokinetic mixing methods in poly(ethylene terephthalate)/montmorillonite nanocomposites

AbstractThe scope of this study consists in studying the effects of processing type on thermal stability of poly(ethylene terephthalate) (PET) and its nanocomposites prepared with organically modified clays. To achieve this goal, an intercalating agent was synthesized and montmorillonite type of clay modified with this intercalating agent was mixed with the PET by using melt extrusion and high‐shear thermokinetic mixing method. According to the results, manganese in the raw clay—though chemically bound—was found to be responsible for the decreased intrinsic viscosity (IV) values, i.e. decreased molecular weight in PET/organoclay nanocomposites. Besides, it was revealed that working on the thermokinetic mixer provided substantial contributions such as shorter processing times in comparison to the melt extrusion method, elimination of drying step before melt processing, which has been accepted as an inevitable process for PET so far, less thermal degradation because of short processing times, and more homogeneous and better dispersion of the clay particles in PET matrix phase. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers

PA6 and Kevlar fiber reinforced isotactic polypropylene: Structure, mechanical properties and crystallization and melting behavior

To improve the thermal and mechanical properties of isotactic polypropylene (iPP), iPP/Kevlar fiber (KF)/polyamide 6 (PA6) composites were prepared via the melt-extrusion method on twin-screw extruder. Kevlar fiber was modified with caprolactam using toluenediisocyanate (TDI) as bridge. The microstructure of modified KF was successfully characterized by Fourier transform infrared (FT-IR), X-ray photoelectron spectrometer (XPS) and scanning electron microscopy (SEM), the results showed that KF was bonded with caprolactam and became coarser. Then the modified KF was introduced into iPP, the composites have better mechanical and thermal properties, implying that modification of KF was helpful to improve the interfacial interaction of iPP/KF/PA6 composites. Besides, the crystallization curves indicated that crystallization behavior of PA6 in the composites was homogeneous and fractional. Furthermore, compatibilizer content played an important role in the mechanical and thermal properties of composites.

Effects of Wood Fiber Content on Structure and Properties of WF/PLA Bio-Composites

This study is devoted to investigate the effects of wood fiber content on structure and properties of wood fiber /poly(lactic acid) bio-composites (WF/PLA bio-composites). The WF/PLA bio-composites with WF from 30% to 60% and from 70% to 90% were prepared using melt extrusion and high-speed mixing methods respectively. The physical, mechanical, thermal, and macromolecular properties of WF/PLA bio-composites were evaluated. The results are as follows: Density of WF/PLA bio-composites increased when WF increased from 30% to 60%, and decreased when WF increased from 70% to 90%. Water resistance of bio-composite decreased with increasing WF content. The flexural strength of WF/PLA bio-composites were lowered when adding WF into PLA. The flexural strength decreased when WF increased from 30% to 50%, and then increased when WF increased from 60% to 80%. The flexural modulus of the bio-composite was higher than that of PLA without WF. Both n and w of PLA in WF/PLA bio-composite were decreased more than 70% with WF increased. The Tg, Tm values of PLA in the bio-composites were decreased with the WF increased. The cold crystal temperature (Tcc) was decreased with WF increased at low WF content. All the property changes were related to the decreasing of molecular weight of PLA in WF/PLA bio-composites.

Development and In Vitro-In Vivo Evaluation of Polymeric Implants for Continuous Systemic Delivery of Curcumin

The introduction of curcumin into clinics is hindered by its low water solubility and poor bioavailability. To overcome these limitations, we developed curcumin implants using poly (ε-caprolactone) as the polymeric matrix. Implants were prepared by melt-extrusion method; in vitro drug release was optimized for effects of polymer composition, drug load, surface area and water-soluble additives. Implants were also tested under in vivo conditions for cumulative curcumin release, and liver concentration was correlated with its efficacy to modulate selected xenobiotic-metabolizing enzymes (CYP1A1 and GSTM). Drug release from implants followed biphasic release pattern with Higuchi kinetics and was proportional to the surface area of implants. Drug release increased proportionately from 2 to 10% (w/w) drug load, and incorporation of 10% (w/w) of water-soluble additives (F-68, PEG 8000 and cyclodextrin) did not significantly alter the drug release. In vivo drug release was found to be ~1.8 times higher than in vitro release. Curcumin was detected at 60 ± 20 ng/g in the liver after four days of implantation and was almost constant (8-15 ng/g) for up to 35 days. This time-dependent drop in curcumin level was found to be due to induction of CYP1A1 and GSTM (μ) enzymes which led to increased metabolism of curcumin. Our data showed that these implants were able to release curcumin for long duration and to modulate liver phase I and phase II enzymes, demonstrating curcumin's biological efficacy delivered via this delivery system.

Preparation and characterization of poly(propylene carbonate)/polystyrene composite films by melt-extrusion method

AbstractPoly(propylene carbonate) (PPC) is a new biodegradable aliphatic polycarbonate with poor thermal stability and mechanical properties which shows difficulty in forming film by melt-extrusion technology. Through the addition of polystyrene (PS), the melt-extrusion film processability, thermal stability and mechanical properties of PPC was improved largely. PPC/PS films were prepared in the the melt-extrusion process successfully. DSC data showed that there was some degree of miscibility between PPC and PS. SEM showed good dispersion of PS particles into PPC matrix. Improved mechanical properties and thermal stability of PPC/PS blends were attributed to homogeneous dispersing and stronger interfacial interaction of PS and PPC. These results indicate that blending PPC with PS is an efficient and convenient method to improve the properties of PPC, and the composites can be used as a common packaging material for a wide range of applications.

Improving the mechanical properties of thermoplastic starch/poly(vinyl alcohol)/clay nanocomposites

Thermoplastic starch/poly(vinyl alcohol) (PVOH)/clay nanocomposites, exhibiting the intercalated and exfoliated structures, were prepared via melt extrusion method. The effects of clay cation, water, PVOH and clay contents on clay intercalation and mechanical properties of nanocomposites were investigated. The experiments were carried out according to the Taguchi experimental design method. Montmorillonite (MMT) with three types of cation or modifier (Na +, alkyl ammonium ion, and citric acid) was examined. The prepared nanocomposites with modified montmorillonite indicated a mechanical improvement in the properties in comparison with pristine MMT. It was also observed that increases in tensile strength and modulus would be attained for nanocomposite samples with 10%, 5% and 4% (by weight) of water, PVOH and clay loading, respectively. The clay intercalation was examined by X-ray diffraction (XRD) patterns. The chemical structure and morphology of the optimum sample was also probed by FTIR spectroscopy and transmission electron microscopy (TEM).