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Model Drug (model + drug)
Selected AbstractsSynthesis, Characterization and Drug Release Behavior of pH-Responsive O-carboxymethyl Chitosan-graft-poly(N-vinylpyrrolidone) Hydrogel Beads,ADVANCED ENGINEERING MATERIALS, Issue 12 2009Liwei Ma In this work, the carboxymethyl chitosan (CMCTS) grafted poly(N-vinylpyrrolidone) (PVP) copolymers were synthesized. The hydrogel beads containing VB2 were prepared from the copolymers by an ionic crosslinked. The experimental results shown that VB2 drug release rate from those beads decreased with the increasing grafting percentage, crosslinker concentration and pH value of the medium. Besides, the beads have the better control ability for releasing of model drug than CMCTS does. [source] Physical and Biological Properties of a Novel Hydrogel Composite Based on Oxidized Alginate, Gelatin and Tricalcium Phosphate for Bone Tissue Engineering,ADVANCED ENGINEERING MATERIALS, Issue 12 2007K. Cai A novel hydrogel composite is reported in this study, which was derived from oxidized alginate, gelatin and tricalcium phosphate (TCP). The physical and biological properties of these hydrogel composites prepared with oxidized sodium alginate with different oxidation degrees were investigated. The drug delivery potential of this hydrogel composite as a carrier was evaluated by using Vitamin B2 as a model drug as well. An in vitro investigation with encapsulation of osteoblast revealed that these composites were biocompatible. This hydrogel composite presented here may be utilized for the fabrication of potential injectable systems for tissue engineering, drug delivery and other medical applications. [source] Synthesis of Magnetic, Up-Conversion Luminescent, and Mesoporous Core,Shell-Structured Nanocomposites as Drug CarriersADVANCED FUNCTIONAL MATERIALS, Issue 7 2010Shili Gai Abstract The synthesis (by a facile two-step sol,gel process), characterization, and application in controlled drug release is reported for monodisperse core,shell-structured Fe3O4@nSiO2@mSiO2@NaYF4: Yb3+, Er3+/Tm3+ nanocomposites with mesoporous, up-conversion luminescent, and magnetic properties. The nanocomposites show typical ordered mesoporous characteristics and a monodisperse spherical morphology with narrow size distribution (around 80,nm). In addition, they exhibit high magnetization (38.0,emu g,1, thus it is possible for drug targeting under a foreign magnetic field) and unique up-conversion emission (green for Yb3+/Er3+ and blue for Yb3+/Tm3+) under 980,nm laser excitation even after loading with drug molecules. Drug release tests suggest that the multifunctional nanocomposites have a controlled drug release property. Interestingly, the up-conversion emission intensity of the multifunctional carrier increases with the released amount of model drug, thus allowing the release process to be monitored and tracked by the change of photoluminescence intensity. This composite can act as a multifunctional drug carrier system, which can realize the targeting and monitoring of drugs simultaneously. [source] Application of the biodegradable diblock copolymer poly(L -lactide)- block -poly(L -cysteine): Drug delivery and protein conjugationJOURNAL OF APPLIED POLYMER SCIENCE, Issue 3 2010Jing Sun Abstract A novel approach to self-assembled and shell-crosslinked (SCL) micelles from the diblock copolymer poly(L -lactide)- block -poly(L -cysteine) to be used as drug and protein delivery carriers is described. Rifampicin was used as a model drug. The drug-loaded SCL micelles were obtained by self-assembly of the copolymer in the presence of the drug in aqueous media. Their morphology and size were studied with dynamic light scattering and field emission scanning electron microscopy. The rifampicin loading capacity and encapsulation efficiency were studied with ultraviolet,visible spectrophotometry. The drug-release rate in vitro depended on the oxidizing and reducing environment. Moreover, a straightforward approach to the conjugation of the copolymer with bovine serum albumin (BSA) was developed, and a gel electrophoresis test demonstrated that this conjugated BSA could be reversibly released from the copolymer substrate under reducing conditions. In conclusion, this L -cysteine copolymer can be used in drug delivery and in protein fixation and recovery. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source] Preparation and characterization of interpenetration polymer network films based on poly(vinyl alcohol) and poly(acrylic acid) for drug deliveryJOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2008Yu-Mei Yue Abstract A series of full interpenetrating polymer network (full-IPN) films of poly(acrylic acid) (PAA)/poly (vinyl alcohol) (PVA) were prepared by radical solution polymerization and sequential IPN technology. Attenuated total reflectance-Fourier transform infrared spectroscopy, swelling properties, mechanical properties, morphology, and glass transition temperature of the films were investigated. FTIR spectra analysis showed that new interaction hydrogen bonds between PVA and PAA were formed. Swelling property of the films in distilled water and different pH buffer solution was studied. Swelling ratio increased with increasing PAA content of IPN films in all media, and swelling ratio decreased with increasing PVA crosslink degree. Tensile strength and elongation at break related not only to the constitution of IPNs but also to the swelling ratio of IPNs. Mechanical property of glutaraldehyde (0.5%) for poly(vinyl alcohol) crosslinking was better than that of glutaraldehyde (1.0%). DSC of the IPN films showed only a single glass transition temperature (Tg) for each sample, and Tg data showed a linear relationship with network composition. Morphology was observed a homogeneous structure, indicating the good compatibility and miscibility between PAA and PVA. Potential application of the IPN films in controlled drug delivery was also examined using crystal violet as a model drug. The release rate of the drug was higher at 37°C than 25°C for all IPNs and also increased slightly with decreasing of poly(acrylic acid) content. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Faster and stronger vascular "Biotube" graft fabrication in vivo using a novel nicotine-containing moldJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2009Osamu Sakai Abstract To accelerate the fabrication of in vivo -tissue engineered autologous vascular prosthetic tissues, the "Biotube," a novel drug-coating mold was designed. The mold was prepared by impregnating nicotine as a model drug into a gelatinous matrix coated on acrylate rods (diameter, 2 mm; length, 20 mm). Upon embedding the molds into dorsal subcutaneous pouches of rats, completely encapsulated Biotubes with significant tissue migration accompanied by rich angiogenesis and having 3.8 times as many neovessels as the uncoated controls, were formed at only 2 weeks. The wall thickness and burst strength of the Biotubes were 399.9 ± 135.2 ,m and 2682.6 ± 722.6 mmHg, respectively. These values were, respectively, more than 9.6 and 3.2 times greater than the corresponding controls. Therefore, it is confidently expected that the mechanical properties of Biotubes obtained by nicotine coating make them suitable for application as vascular grafts. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009 [source] Combined application of extrusion-spheronization and hot-melt coating technologies for improving moisture-proofing of herbal extractsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2010Hao Chen Abstract The aim of this research was to investigate the moisture-proofing effect and its mechanism for herbal extracts using extrusion-spheronization combined with hot-melt coating. Guizhi Fuling (GF) compound herbal extract with high hygroscopicity was used as a model drug. In the process of extrusion-spheronization, pellets containing 100% GF were prepared, and then coated with hot-melt coating material using a traditional coating pan. The moisture sorption data for GF were determined by storage at a series of different relative humidities. When the pellets were coated with a 96:4 mixture of stearic acid and polyethylene glycol 6000, the cumulative drug release was over 90% at 45,min while the moisture content was 4.9% at 75% RH within 10 days. These pellets have better moisture-proofing than those coated with Opadry AMB at the same coating level due to a different moisture sorption mechanism. The moisture sorption behavior of the hot-melt coating can be attributed to water vapor diffusion via a porous matrix system, while the Opadry AMB coating system involved a swelling controlled system. The Higuchi model was the best fit for the moisture sorption of the hot-melt coating in all formulations whereas the Opadry AMB coating fitted the Nuttanan model. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2444,2454, 2010 [source] Improved physical stability of amorphous state through acid base interactionsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2009Chitra Telang Abstract To investigate role of specific interactions in aiding formation and stabilization of amorphous state in ternary and binary dispersions of a weakly acidic drug. Indomethacin (IMC), meglumine (MU), and polyvinyl pyrollidone (PVP) were the model drug, base, and polymer, respectively. Dispersions were prepared using solvent evaporation. Physical mixtures were cryogenically coground. XRPD, PLM, DSC, TGA, and FTIR were used for characterization. MU has a high crystallization tendency and is characterized by a low Tg (17°C). IMC crystallization was inhibited in ternary dispersion with MU compared to IMC/PVP alone. An amorphous state formed readily even in coground mixtures. Spectroscopic data are indicative of an IMC,MU amorphous salt and supports solid-state proton transfer. IMC,MU salt displays a low Tg,,,50°C, but is more physically stable than IMC, which in molecular mixtures with MU, resisted crystallization even when present in stoichiometric excess of base. This is likely due to a disrupted local structure of amorphous IMC due to specific interactions. IMC showed improved physical stability on incorporating MU in polymer, in spite of low Tg of the base indicating that chemical interactions play a dominant role in physical stabilization. Salt formation could be induced thermally and mechanically. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2149,2159, 2009 [source] Drug,polymer interaction and its significance on the physical stability of nifedipine amorphous dispersion in microparticles of an ammonio methacrylate copolymer and ethylcellulose binary blendJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2008Jingjun Huang Abstract Using spectroscopic and thermal analysis, this study investigated drug,polymer interaction and its significance on the physical stability of drug amorphous dispersion in microparticles of an ammonio polymethacrylate copolymer (Eudragit RL®) (RL) and ethylcellulose (EC) binary blend (RL/EC,=,2:1 w/w) prepared for use in controlled release of poorly water-soluble drugs. Solid dispersion of the model drug, nifedipine in the microparticles could be described as an ideal amorphous mixture for drug loadings up to 11% w/w. The antiplasticizing effect of the polymer blend was indicated by a significant increase in the glass transition point from ,50°C for the amorphous nifedipine to ,115°C for its solid solution. Moreover, shifts in infrared vibration wavenumber of nifedipine carbonyl and amine groups suggested that the hydrogen bonds (H-bonds) originally formed among nifedipine molecules were broken and replaced by those formed between nifedipine and polymers in the microparticles. Further infrared analysis on nifedipine amorphous dispersions with a single polymer, namely RL or EC, confirmed the proposed hydrogen-bonding interactions; and their stability study results suggested that both antiplasticizing effects and hydrogen bonding of EC and RL with nifedipine might be responsible for the physical stability of the microparticles of nifedipine amorphous dispersion with a RL/EC binary blend. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:251,262, 2008 [source] Drug release properties of polymer coated ion-exchange resin complexes: Experimental and theoretical evaluationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2007Seong Hoon Jeong Abstract Although ion-exchange resins have been used widely as drug delivery systems, their exact release kinetics has not been reported yet. Usually only the rate-limiting step has been taken into account and the rest of the steps have been ignored as instantaneous processes. To investigate the exact release kinetics of polymer-coated drug/ion-exchange resin complexes for sustained drug delivery, the results of new mathematical modeling were compared with experimental results. Drug/resin complexes with a model drug, dextromethorphan, were prepared and used as cores for fluid-bed coating. An aqueous colloidal dispersion of poly(vinyl acetate) was applied for the coating. A comprehensive mathematical model was developed using a mechanistic approach by considering diffusion, swelling, and ion-exchange processes solved by numerical techniques. The rate-limiting factor of the uncoated resin particles was diffusion through the core matrix. Similarly, in the coated particles the rate-limiting factor was diffusion through the coating membrane. The mathematical model has captured the phenomena observed during experimental evaluations and the release dynamics from uncoated and coated (at different coat levels) particles were predicted accurately (maximum RMSE 2.4%). The mathematical model is a useful tool to theoretically evaluate the drug release properties from coated ion-exchange complexes thus can be used for design purposes. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci [source] Sulfoalkyl ether-alkyl ether cyclodextrin derivatives, their synthesis, NMR characterization, and binding of 6,-methylprednisoloneJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2005Serena Tongiani Abstract The objective of this study is to see if random alkyl ethers of various sulfoalkyl ether cyclodextrins can be synthesized and characterized. The purpose of the alkylation was to test the hypothesis that an increase in the "height" of a cyclodextrins cavity would help in the binding/complexation of larger more structurally complex molecules. The synthesis of new cyclodextrin derivatives comprising a mixture of sulfoalkyl ether and alkyl ether substituents on the same cyclodextrin ring was performed in aqueous alkaline solutions using various sultones and alkylsulfates. The method presented provided an easy and efficient way to modify cyclodextrins avoiding the use of organic solvents and high quantities of alkylating agents and could be carried out in either a two step or "one pot" single step process. Purification was by neutralization followed by ultrafiltration. The derivatives were characterized by 1D, (1H and 13C), and a 2D NMR technique (HMQC, Heteronuclear Multiple Quantum Coherence). The combination of these techniques allowed an analysis of the degree of substitution and the site of substitution on the cyclodextrin (CD) nucleus. For both ,- and ,-CD, sulfoakylation was preferred on the 2,>,3,>,6 hydroxyls while alkylation was preferred 6,>,2,>,3. Due to the simultaneous presence of short alkyl ether chains and negatively charged sulfoalkyl ether chains, these mixed water-soluble cyclodextrin derivatives, especially those of ,-cyclodextrin, should be able to bind more complex drugs. The improved binding capacity of these new modified CDs with the model drug 6,-methylprednisolone is reported. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2380-2392, 2005 [source] Effect of chloride ion on dissolution of different salt forms of haloperidol, a model basic drugJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2005Shoufeng Li Abstract The effect of chloride ion (Cl,) on dissolution rates of hydrochloride, mesylate (methanesulfonate) and phosphate salt forms of a model drug, haloperidol, was investigated. The dissolution rates of the salts in 0.01M HCl from rotating disks followed the order of mesylate,,,phosphate,>,hydrochloride. With additional chloride ion, a decrease in dissolution rate of the hydrochloride salt was observed due to the common ion effect. Dissolution rates of mesylate and phosphate salts also decreased due to their conversion to the HCl salt form on the surfaces of dissolving disks, however, the dissolution rates of mesylate and phosphate salts under identical chloride ion concentrations were still higher than that of the HCl salt. In powder dissolution studies, it was observed that kinetics of nonhydrochloride-to-hydrochloride salt conversion play a major role in dissolution; the mesylate dissolved completely (<5 min) before its dissolution rate could be impeded by its conversion to the hydrochloride salt form. Therefore, despite the potential for conversion to a hydrochloride salt form, certain nonhydrochloride salt forms may still be preferred for dosage form development due to kinetic advantages during dissolution, such as higher apparent dissolution rate of a nonhydrochloride salt before it could completely convert to the hydrochloride form. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2224,2231, 2005 [source] Small-molecule release from poly(D,L -lactide)/poly(D,L -lactide-co-glycolide) composite microparticlesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2005Emily J. Pollauf Abstract Addition of biodegradable polymer shells surrounding polymeric, drug-loaded microparticles offers the opportunity to control drug release rates. A novel fabrication method was used to produce microparticles with precise control of particle diameter and the thickness of the polymer shell. The effect of shell thickness on release of a model drug, piroxicam, has been clearly shown for 2- to 15-µm thick shells of poly(D,L -lactide) (PDLL) surrounding a poly(D,L -lactide-co-glycolide) (PLG) core and compared to pure PLG microspheres loaded with piroxicam. Furthermore, the core-shell microparticles are compared to microspheres containing blended polymers in the same mass ratios to demonstrate the importance of the core-shell morphology. Combining PDLL(PLG) microcapsules of different shell thicknesses allows nearly constant release rates to be attained for a period of 6 weeks. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2013,2022, 2005 [source] Microemulsions as colloidal vehicle systems for dermal drug delivery.JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2005Part V: Microemulsions without, with glycolipid as penetration enhancer Abstract The aim of this study was to investigate the dermal administration of a highly hydrophilic model drug, diphenhydramine (DPH), in colloidal systems with an aqueous colloidal phase in the presence of a glycolipid (GL) as a penetration modifier. Dermal penetration of DPH, GL, and isopropylpalmitate (IPP) from ME systems without GL and with GL as well as from a hydrogel used as standard formulation were estimated in vitro using human skin. The penetration of the drug, the oil (IPP), and the GL was measured with highly sensitive HPLC, HPLC-MS, and GC-MS assays, respectively. It could be shown that penetration modifier GL is penetrating very fast, and to a high extent into and through the human skin. In contrast, the penetration of IPP used as oily phase in the ME is limited. When incorporated in the ME systems GL and DPH was accumulated in the viable epidermis and in the dermis. Using ME containing a penetration modifier such as GL, a slight additional enhancing effect could be observed, particularly concerning the penetration of DPH into the acceptor fluid when a highly hydrophilic drug such as DPH was applied. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:821,827, 2005 [source] Identification of the most relevant factors that affect and reflect the quality of granules by application of canonical and cluster analysisJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2002Vitor H. Dias Abstract The production of granules by wet granulation in a fluidized bed was assessed according to two statistical techniques to identify the most relevant factors that affect the quality of the granules. The statistics used include Canonical Analysis and Cluster Analysis. The factors studied, according to a center of gravity design, included the solubility of a model drug, different grades of polyvinylpirrolidone (PVP), the polarity and the rate of administration of the granulation solution, the atomizing air pressure, the inlet air pressure and rate. The properties of the granules considered were the yield, the assay of the drug, the size, the densities (true, bulk and tapped), the friability, the flowability and one compressibility index. Statistical analysis of the factors evaluated has shown that the solubility of the materials and the pressure of the atomizing air in the nozzle were the most critical parameters affecting the quality of the granules. Less relevant were the granulation solution and the grade of PVP. The properties of the granules that best described their quality were the yield and the densities. From the Cluster Analysis it was possible to divide the granules in two clusters, where cluster 1 was identifiable by the yield, the assay, the flowability, and the friability, whereas cluster 2 was better identified by the size of the granules. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:273,281, 2002 [source] Preparation and evaluation of a novel delayed-onset sustained-release system of propranolol hydrochlorideJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2008Xue-mei Feng The objective of this work was to prepare and evaluate a new delayed-onset sustained-release system, comprising a sustained-release core tablet with hydroxypropyl methylcellulose as polymer matrix and an ethylcellulose/Eudragit L coating capable of delaying the drug release. The sustained core containing propranolol hydrochloride as the model drug was prepared by granulate tableting and the polymer coating was applied in a computer-controlled coating pan. The dissolution tests demonstrated that the in-vitro drug release was pH-dependent with sufficient gastric resistance, and the lag time (t10%) could be controlled by adjusting the coating level. Three dosage forms including commercial tablet, sustained-release tablet and the delayed-onset sustained-release tablet were administrated to six beagle dogs and the plasma levels of propranolol hydrochloride were measured with high-performance liquid chromatography. The delayed-onset sustained-release tablet had a lag time of 3.0 h in-vitro and 3.5 h in-vivo, and a tmax of 7.0 h. The relative bioavailability for delayed-onset sustained-release tablet was 96.98% compared with commercial tablets. The results indicate that the new propranolol delayed-onset sustained-release system could achieve a relatively constant drug release followed by a programmed lag time, and this may provide a promising drug delivery form for chronopharmacotherapy of certain cardiovascular diseases. [source] Mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid using porcine buccal and vaginal tissue, Caco-2 cell lines, and rat jejunumJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2004Giuseppina Sandri The influence of the molecular weight on mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid (1878, 693 and 202 kDa) has been evaluated. The mucoadhesive properties were investigated using buccal and vaginal porcine mucosa by means of a tensile stress method and using rat jejunum by means of an inclined plane method. The mucoadhesive performances observed using animal tissues were compared with the mucoadhesive properties observed using submaxillary or gastric mucin dispersions. The penetration enhancement properties were investigated using porcine buccal epithelium membrane or vaginal tissue and a cell monolayer (Caco-2 cell line). Chitosan hydrochloride, already described as a penetration enhancer towards buccal and vaginal mucosae and Caco-2 cell monolayers, was used as reference. Aciclovir (acyclovir), a poorly soluble and absorbable drug, commonly used in the treatment of Herpes simplex virus (type I and II), was used as the model drug. Unlike chitosan hydrochloride, which does not show any mucoadhesive potential at pH close to neutrality (buccal and intestinal), all hyaluronic acid grades show mucoadhesive properties in all the environments considered (buccal, vaginal and intestinal). In all cases, a decrease in molecular weight of hyaluronic acid produced an increase in the mucoadhesive performance. The hyaluronic acid with the lowest molecular weight (202 kD) exhibited the best penetration enhancement properties, that, depending on the substrate under consideration, was either comparable with or even better than chitosan hydrochloride. Therefore, this grade would be the most promising for buccal, vaginal and intestinal delivery of aciclovir. [source] Comparison of the lymphatic transport of a lipophilic drug from vehicles containing ,-tocopherol and/or triglycerides in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2001P. B. Nielsen The applicability of ,-tocopherol as a lymphotropic carrier for a highly lipophilic drug has been evaluated. Transport to the intestinal lymph of the highly lipophilic model drug, Lu28,179, in rats after administration to the stomach in an ,-tocopherol emulsion was compared with lymphatic transport after administration of a sesame oil emulsion and an ,-tocopherol/sesame oil emulsion. Lymphatic transport of the triglycerides and of ,-tocopherol was determined. A conscious rat model was used, and the mesenteric lymph was collected. There was no significant difference between the cumulative masses of triglyceride from the two emulsions containing triglyceride 24 h after administration. Administration of an ,-tocopherol emulsion seemed to induce mobilization of endogenous triglyceride. The lymphatic transport of ,-tocopherol was less than 1 mg 24 h after administration of both emulsions containing ,-tocopherol. The absorption of Lu28,179 from the ,-tocopherol emulsion was very low, with a lymphatic recovery of 0.05%. When administered in an ,-tocopherol/sesame oil emulsion, the recovery of Lu28,179 increased sevenfold to 0.35%. However, after administration of Lu28,179 in a sesame oil emulsion, the lymphatic recovery increased a further 13-fold to 4.5%. In conclusion, the study showed that ,-tocopherol did not promote lymphatic absorption of Lu28,179 and thus was not a good lymphotropic carrier, as compared with sesame oil. ,-Tocopherol in combination with sesame oil was not a good lymphotropic carrier either. The non-absorbed ,-tocopherol fraction in the intestine might be able to prevent the absorption of Lu28,179. [source] Colon Delivery Efficiencies of Intestinal Pressure-controlled Colon Delivery Capsules Prepared by a Coating Machine in Human SubjectsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2000ZHAOPENG HU Large quantities of pressure-controlled colon delivery capsules (PCDCs) were prepared by a Hicoater-mini pharmaceutical coating machine and colon delivery efficiencies were evaluated in man. Caffeine powder as a model drug was suspended with a polyethylene glycol (PEG) 1000 suppository base at 50°C, and was hardened in no. 0- and no. 2-sized capsular shapes. The capsule-shaped suppositories were coated with 5% w/v ethanolic ethylcellulose (7G grade) solution using the coating machine. By increasing the coating weight of ethylcellulose from 28.6 ± 1.1 mg to 45.3 ± 0.2 mg, the mean coating thickness of no. 0 PCDCs increased from 56 ± 1 ,m to 64 ± 1 ,m. With no. 2 PCDCs, the mean coating thickness increased from 50 ± 1 ,m to 57 ± 1 ,m by increasing the coating weight of ethylcellulose from 8.1 ± 0.5 mg to 11.2 ± 0.3 mg. The no. 0 PCDCs, having a mean ethylcellulose coating membrane thicknesses of 56± 1 ,m (type 1) and 64 ± 1 ,m (type 2), as well as no. 2 PCDCs, having thicknesses of 50 ± 1 ,m (type 3) and 57 ± 1 ,m (type 4), were used for in-vivo evaluation in man. After oral administration of test preparations containing 75 mg of caffeine, saliva samples were obtained and salivary caffeine levels were measured by an HPLC method. The first appearance time, Ti, of caffeine in the saliva was used as a parameter for the estimation of the release time of caffeine from PCDCs in the gastrointestinal tract. The mean Ti values of no. 0 PCDCs were 3.3 ± 0.3 h for type-1 and 5.3 ± 0.3 h for type-2 preparations while the mean Ti values of no. 2 PCDCs were 4.3 ± 0.5 h for type 3 and 5.3 ± 0.3 h for type 4. There were good correlations between ethylcellulose coating membrane thicknesses and in-vivo Ti values. A colon arrival time of 5 h was reported in our subjects by gastrointestinal magnetomarkergraphy. PCDCs having a mean coating thickness of 64± 1 ,m for no. 0 capsules and of 57 ± 1 ,m for no. 2 capsules were thought to deliver caffeine to the human colon efficiently. [source] The Encapsulation of Bleomycin Within Chitosan Based Polymeric Vesicles Does Not Alter its BiodistributionJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2000J. SLUDDEN Polymeric vesicles have recently been developed from an amphiphilic chitosan derivative,palmitoyl glycol chitosan. Their potential as a drug delivery system was evaluated using the anti-cancer compound bleomycin as a model drug. Palmitoyl glycol chitosan (GCP41) was synthesised by conjugation of palmitoyl groups to glycol chitosan. Bleomycin-containing vesicles (669 nm diameter) were prepared from a mixture of GCP41 and cholesterol by remote loading. The vesicles were imaged by freeze-fracture electron microscopy and their in-vitro stability tested. Incubation of the larger vesicles with plasma in-vitro led to a reduction of mean size by 49%, a reaction not seen with control sorbitan monostearate niosomes (215 nm in size). They also showed a higher initial drug release (1 h), but GCP41 and sorbitan monostearate vesicles retained 62% and 63% of the encapsulated drug after 24 h, respectively. The biodistribution of smaller vesicles (290 nm) prepared by extrusion through a 200-nm filter was also studied in male Balb/c mice. Encapsulation of bleomycin into polymeric vesicles did not significantly alter the pharmacokinetics of biodistribution of bleomycin in male Balb/c mice although plasma and kidney levels were slightly increased. It is concluded that the extruded GCP41 vesicles break down in plasma in-vivo and hence are unlikely to offer any therapeutic advantage over the free drug. [source] Dispersion polymerization of vinyl monomers in supercritical carbon dioxide in the presence of drug molecules: A one-pot route for the preparation of controlled delivery systemsJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 22 2008Alessandro Galia Abstract The polymerization of 1-vinyl-2-pyrrolidone in supercritical carbon dioxide in the presence of ibuprofen as a model drug was investigated as a new one-pot process for the preparation of polymer-based drug delivery systems (DDSs). The composites were prepared at 65 °C and P = 31,42 MPa by changing the initial concentration of the drug and the concentration of a crosslinking agent and that of a hydrophobic comonomer. The effects of these parameters on the performances of the polymerization and on the in vitro release kinetics of ibuprofen were studied. In all the experiments, part of the drug was entrapped inside the polymer particles and dissolved more slowly with respect to the pure compound. Copolymerization with methyl methacrylate was the most effective route to obtain a DDS with sustained temporal release of the drug molecule. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7429,7446, 2008 [source] Synthesis and supramolecular self-assembly of thermosensitive amphiphilic star copolymers based on a hyperbranched polyether coreJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 2 2008Haiyan Hong Abstract A novel amphiphilic thermosensitive star copolymer with a hydrophobic hyperbranched poly (3-ethyl-3-(hydroxymethyl)oxetane) (HBPO) core and many hydrophilic poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) arms was synthesized and used as the precursor for the aqueous solution self-assembly. All the copolymers directly aggregated into core,shell unimolecular micelles (around 10 nm) and size-controllable large multimolecular micelles (around 100 nm) in water at room temperature, according to pyrene probe fluorescence spectrometry and 1H NMR, TEM, and DLS measurements. The star copolymers also underwent sharp, thermosensitive phase transitions at a lower critical solution temperature (LCST), which were proved to be originated from the secondary aggregation of the large micelles driven by increasing hydrophobic interaction due to the dehydration of PDMAEMA shells on heating. A quantitative variable temperature NMR analysis method was designed by using potassium hydrogen phthalate as an external standard and displayed great potential to evaluate the LCST transition at the molecular level. The drug loading and temperature-dependent release properties of HBPO- star -PDMAEMA micelles were also investigated by using indomethacin as a model drug. The indomethacin-loaded micelles displayed a rapid drug release at a temperature around LCST. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 668,681, 2008 [source] Morphology and temperature responsiveness,swelling relationship of poly(N -isopropylamide,chitosan) copolymers and their application to drug releaseJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 12 2004Chia-Fen Lee Abstract Poly [N -isopropylacrylamide (NIPAAm),chitosan] crosslinked copolymer particles were synthesized by soapless emulsion copolymerization of NIPAAm and chitosan. An anionic initiator [ammonium persulfate (APS)] and a cationic initiator [2,2,-azobis(2-methylpropionamidine)dihydrochloride (AIBA)] were used to initiate the reaction of copolymerization. The chitosan,NIPAAm copolymer synthesized by using APS as the initiator showed a homogeneous morphology and exhibited the characteristic of a lower critical solution temperature (LCST). The copolymer synthesized by using AIBA as an initiator showed a core,shell morphology, and the characteristic of LCST was insignificant. The LCST of the chitosan,NIPAAm copolymer depended on the morphology of the copolymer particles. In addition, the chitosan,NIPAAm copolymer particles were processed to form copolymer disks. Then, the effect of various variables such as the chitosan/NIPAAm weight ratio, the concentration of crosslinking agent, and the pH values on the swelling ratio of chitosan,NIPAAm copolymer disks were investigated. Furthermore, caffeine was used as the model drug to study the characteristics of drug loading of the chitosan,NIPAAm copolymer disks. Variables such as the chitosan/NIPAAm weight ratio and the concentration of the crosslinking agent significantly influenced the behavior of caffeine loading. Two factors (pore size and swelling ratio) affected the behavior of caffeine release from the chitosan,NIPAAm copolymer disks. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3029,3037, 2004 [source] Design and in vitro Biodegradation of Novel Hepatocyte-Targetable (Galactose Polycation/Hemoglobin) Multilayers and MicrocapsulesMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 12 2009Fu Zhang Abstract The formation of novel hepatocyte-targetable and biodegradable polycation/protein multilayers and hollow microcapsules by LbL assembly is reported, in which galactose residues allow for targetability and Hb acts as a main degradable component. The in vitro biodegradability of multilayers via proteases was evaluated in detail on both planar substrates and CaCO3 particles followed by UV-Vis, SEM, and AFM characterizations. The degradation approximately follows an exponential decay, and the relation between the kinetic constant k and the number n of deposited bilayers is well approximated by a power equation. Sustained release of the encapsulated model drug was attained by using enzymatic degradation of hollow capsules. [source] Thermosensitive and Dissolution Properties in Nanocomposite Polymer HydrogelsMACROMOLECULAR RAPID COMMUNICATIONS, Issue 17 2009Chia-Jung Wu Abstract We investigate the phase transition behavior and dissolution resistant properties of thermo-sensitive nanocomposite hydrogels made from PEO-PPO-PEO triblock copolymer (Pluronic F127) and Laponite silicate nanoparticles. The rapid dissolution properties of F127 copolymer hydrogels usually limit their use as sustained release drug carriers. We overcome this limitation by synergistic combination of nanoparticle gelation characteristics with polymer thermo-sensitivity. We present a proof of concept that the temperature-dependent phase transitions can be shifted as a function of hydrogel composition and that the dissolution of the polymer hydrogels as well as the release of a model drug, albumin, can be significantly slowed down by addition of nanoparticles. The dissolution resistant properties generated will prove useful in the future formulation, processing and application of our polymer hydrogels for sustained release drug delivery carriers. [source] Development of New Microencapsulation Techniques Useful for the Preparation of PLGA MicrospheresMACROMOLECULAR RAPID COMMUNICATIONS, Issue 21 2006Hongkee Sah Abstract Summary: Intensive efforts were made to develop an efficient, novel microencapsulation system useful to encapsulate a model drug, risperidone, to PLGA microspheres. Methyl dichloroacetate was used as a dispersed solvent for the first time, since it possessed excellent solvency power on PLGA and readily underwent ammonolysis. A dispersed phase composed of methyl dichloroacetate, risperidone, and PLGA was emulsified in an aqueous phase to form an O/W emulsion. Adding ammonia solution into the emulsion rapidly converted methyl dichloroacetate into water-soluble dichloroacetamide and methanol. As a result, emulsion droplets were immediately transformed into hardened microspheres. The new microencapsulation system allowed us to make PLGA microspheres with a drug payload of >40 wt.-% and attain almost complete encapsulation efficiencies. In summary, preparing an O/W emulsion and subjecting the emulsion to ammonolysis led to development of an efficient, novel microencapsulation system. It was anticipated that the new system could make it possible to load other bioactive materials into microspheres made of various types of hydrophobic polymers. SEM micrographs of the external and internal morphology of PLGA/risperidone microspheres. [source] Chitosan-Pectin Composite Gel Spheres: Effect of Some Formulation Variables on Drug ReleaseMACROMOLECULAR SYMPOSIA, Issue 1 2004Pornsak Sriamornsak Abstract Chitosan-pectin composite gel spheres were prepared by ionotropic gelation method. Pectin solution containing indomethacin, a model drug, was extruded into a mixture of chitosan and calcium chloride. The release behavior of indomethacin from composite gel spheres was investigated in-vitro. The influence of factors affecting release behavior, such as type of pectin, molecular weight of chitosan, cross-linking time and release medium, were discussed in this study. Adding chitosan into gelation medium could retard the release of indomethacin from gel spheres. The different type of pectin used demonstrated slightly different drug release profiles. The higher molecular weight of chitosan showed less indomethacin release than the lower one. The increased cross-linking time slowed the drug release from composite gel spheres. The release of indomethacin from composite gel spheres was also dependent on the release medium. The drug release was slower in tris buffer where no phosphate ions which can induce the precipitation of calcium phosphate. The results suggested that the composite gel spheres of pectin and chitosan could be used as a controlled release drug delivery carrier. [source] Interpenetrating polymeric network hydrogels for potential gastrointestinal drug releasePOLYMER INTERNATIONAL, Issue 11 2007Sema Ekici Abstract New interpenetrating polymeric network (IPN) hydrogels based on chitosan (C), poly(N -vinyl pyrrolidone) (PVP) and poly(acrylic acid) (PAAc), crosslinked with glutaraldehyde (G) and N,N,-methylenebisacrylamide (MBA), were prepared and investigated for potential gastrointestinal drug delivery vehicles utilizing a model drug, amoxicillin. IPN hydrogels were synthesized by simultaneous polymerization/crosslinking of acrylic acid monomer in the presence of another polymer (C) and crosslinker (G, MBA). Three different concentrations of glutaraldehyde were used (0.5, 1.0 and 2.0 w/w) to control the overall porosity of the hydrogels, named C-P-AAc/0.5, C-P-AAc/1.0 and C-P-AAc/2.0, respectively. Spectroscopic and thermal analyses such as Fourier transform infrared spectroscopy, thermogravimetric analysis and thermomechanical analysis were performed for IPN characterization. Equilibrium swelling studies were conducted for pH and temperature response behavior. Swelling studies were also carried out in simulated gastric fluid of pH = 1.1 and simulated intestinal fluid of pH = 7.4 to investigate possible site-specific drug delivery. It was found that the release behavior of the drug from these IPN hydrogels was dependent on the pH of the medium and the proportion of crosslinker in the IPN. It was observed that amoxicillin release at pH = 7.4 was higher than at pH = 1.1. The analysis of the drug release showed that amoxicillin was released from these hydrogels through a non-Fickian diffusion mechanism. Copyright © 2007 Society of Chemical Industry [source] Reactivity of ethyl acetate and its derivatives toward ammonolysis: ramifications for ammonolysis-based microencapsulation processPOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 10 2009Younglim Chung Abstract The reactivity of three ester organic solvents toward ammonolysis was examined in relation to the development of an ammonolysis-based microencapsulation process. Ethyl acetate, ethyl chloroacetate, and ethyl fluoroacetate were chosen as ester organic solvents. Progesterone was considered as a model drug to be encapsulated into poly- D, L -lactide- co -glycolide microspheres. A polymeric dispersed phase was emulsified in an aqueous phase, to which ammonia was added to initiate ammonolysis. The polarization status of a carbonyl group in the backbone of the ester was found to decide the magnitude of the ester reactivity. In fact, the simple ester ethyl acetate hardly reacted with ammonia, while ethyl chloroacetate and ethyl fluoroacetate showed greater reactivity toward ammonolysis. The rapid completion of ammonolysis led to the conversion of the water-immiscible solvents into water-soluble solvents, thereby providing an efficient tool for microsphere solidification. Among microencapsulation parameters, the type of dispersed solvent, the molar ratio of ammonia to a dispersed solvent, and the percentage of the progesterone payload decisively influenced the characteristics of the microspheres. Subsequently, variations in such parameters accompanied considerable influence on microsphere morphology, incorporation efficiency, thermal behavior, the degree of residual solvents, and the physical status of progesterone. Optimization of the process parameters would not only contribute to improving the ammonolysis-based microencapsulation process, but would also permit the tailoring of microsphere properties to specific demands. Copyright © 2008 John Wiley & Sons, Ltd. [source] Photopolymerization of alicyclic methacrylate hydrogels for controlled releasePOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 7 2009Jing Han Abstract Alicyclic hydroxy methacrylate monomer, o -hydroxycyclohexyl methacrylate (HCMA), was synthesized and characterized by Fourier transformed infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance spectroscopy (1H-NMR). Photopolymerization kinetics of HCMA was investigated via real-time infrared spectroscopy (RT-IR). Polymeric network hydrogels based on hydroxyethyl methacrylate (HEMA) and HCMA were prepared by using the photopolymerization technique. Mechanical strength, swelling characteristic, and controlled release behavior of hydrogels with various feed compositions were studied. Poly(HEMA-co-HCMA) hydrogel had higher storage modulus than that of poly(HEMA) hydrogel as investigated by dynamic mechanical analysis (DMA). Acid orange 8 was used as a model drug for the investigation of drug release behavior of copolymeric hydrogels. Results indicated that increase in HCMA ratio in hydrogel composition could reduce the swelling rate and prolong the release time. Scanning electron microscopy (SEM) was also utilized to study the surface morphology of hydrogels, and the results indicated that HCMA content influenced pore diameter on the hydrogel surface. Copyright © 2008 John Wiley & Sons, Ltd. [source] | |||||||||||||