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ABSTRACT: We attempted to prepare a subcutaneous pharmaceutical form of warfarin based on a suspension or poly(ε-caprolactone) microparticles to improve patient adherence. The warfarin suspension had a mean particle size of 20.0 μm and in vitro release close to 100% in 72 h. Microparticle size and encapsulation efficiencies ranged from 54.0 to 80.0 μm and 37.0 to 47.0%, respectively. After 72 h, warfarin microparticles exhibited in vitro drug release ranging from 62.0 to 80.0%. Warfarin subcutaneous dosage forms were administered to rabbits. Plasma concentration of warfarin was determined and biological activity was measured by prothrombin time monitoring. The observed relative bioavailabilities calculated from plasma concentrations and prothrombin times were 54.2 and 92.1%, and 61.8 and 61.4% for suspension and microparticles, respectively.
International journal of pharmaceutics 04/2012; 431(1-2):33-8. · 2.96 Impact Factor
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ABSTRACT: The main objective of this study was to prepare two types of nanoparticles with poly(d,l-lactide-co-glycolide) (PLGA) and polyethylenimine (PEI) polymers. Plasmid DNA (pDNA) was adsorbed either on PLGA/PEI nanoparticles, or as PEI/DNA complex onto the surface of PLGA nanoparticles. Both types of nanoparticles were prepared by the double emulsion method. The nanoparticles were characterized by their size, zeta potential and pDNA or PEI/DNA complex adsorption. The PEI/DNA complex adsorption was confirmed with ethidium bromide assay. pDNA adsorption onto PLGA/PEI nanoparticles (PLGA/PEI-DNA) was studied by electrophoresis on agarose gel. Cytotoxicity and transfection efficiency of both types of nanoparticle and PEI/DNA complexes formulations were studied in head and neck squamous carcinoma cell line (FaDu). To improve endosomal release, photochemical internalization (PCI) was used. The zeta potential increased when the PEI/DNA complex adsorbed onto PLGA nanoparticles (PLGA-PEI/DNA). Optimal pDNA adsorption efficiency was achieved for nitrogen/phosphorous ratio≥20/1. In vitro transfection and cells viability on FaDu cells with or without PCI were found to be variable depending on the type and concentration of nanoparticles. The results showed that transfection efficiency for PLGA/PEI-DNA or PLGA-PEI/DNA nanoparticles ranged between 2 and 80%, respectively. PCI was found to slightly improve the transfection efficiency for all formulations.
International journal of pharmaceutics 10/2010; 403(1-2):276-84. · 2.96 Impact Factor
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ABSTRACT: The development of heparin oral form has been a subject of international research for a long time. Promising results have been obtained in vivo in terms of anti-Xa activity with different strategies and notably microparticles but studies concerning the anti-IIa activity and the anti-Xa/anti-IIa ratio have never been presented. Anti-Xa activities, anti-IIa activities and anti-Xa/anti-IIa ratios provided by nadroparin Eudragit RS and poly (D,L-lactic-co-glycolic acid) (PLGA) microparticles were determined in vitro and in vivo and an evaluation of their pharmacokinetic parameters compared to subcutaneous injection was performed. Nadroparin was encapsulated into microparticles prepared by the double emulsion method using Eudragit RS alone or in mixture with PLGA of two kinds, i.e. with (PLGA S) or without (PLGA H) esterification of the acid ending. Microparticles characterisation was performed (size, anti-Xa and anti-IIa activities entrapped and released) before their oral administration in rabbits. In vitro anti-Xa/anti-IIa ratios released from nadroparin microparticles were higher than the ratio of the commercial solution. After oral administration, whatever the formulation, sustained anti-Xa and anti-IIa activities were obtained compared to the subcutaneous injection with a peak concentration at 4 hours (up to 0.59 anti-Xa U/ml and 0.11 anti-IIa U/ml for PLGA S 50% / ERS 50% formulation). Anti-Xa and anti-IIa relative bioavailabilities were high, up to 40% (ERS 100% formulation). Anti-Xa/anti-IIa ratios were within range already obtained for subcutaneous injection, i.e. between 5 and 15. Nadroparin microparticles of nadroparin are promising oral dosage form performing sustained and well controlled anti-Xa, anti-IIa activities and anti-Xa/anti-IIa ratio.
Thrombosis and Haemostasis 04/2010; 103(6):1254-67. · 5.04 Impact Factor
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ABSTRACT: Ivermectin (IVM) is a BCS II drug with potent antiparasitic activity in veterinary applications. In this study, poly(lactide-co-glycolide) (PLGA) and poly(DL-lactide) (PLA) Ivermectin-loaded microparticles were prepared by the simple emulsion (O/W) solvent evaporation method in order to obtain sustained release formulations for parenteral applications. The effects of polymer end-groups (ester or free acid) and the addition of the hydrophilic polyvinylpyrrolidone polymer (PVP) in in vitro drug release profiles were also studied. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis showed that IVM was present in an amorphous state or as a molecular dispersion within the polymers or theirs mixtures with PVP and that a PVP-drug complex was formed. Drug entrapment efficiency in the microparticles (>90%) was independent of the polymer composition, the end groups and the presence of PVP. However, microscopic (SEM) observations showed that the addition of PVP led to more porous microparticles accompanied by the increased rates of drug release.
Journal of Microencapsulation 01/2010; 27(7):609-17. · 1.55 Impact Factor
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ABSTRACT: The development of new vectors to deliver DNA into cells for therapy of cancers or genetic diseases has been a major area of research for many years. However, the clinical application of this technology requires the development of efficient, reliable and sterile vectors enabling the transfer of genes in vivo. Non viral, polymer or lipid-based vectors offer a new impetus to gene therapy because they are less toxic than viral vectors (no endogenous recombination, fewer immunological reactions, easy production and delivery of large-sized plasmid). The aim of this study is to develop a new tool for DNA delivery composed of methacrylic polymeric (Eudragit RS and RL) nanoparticles. These nanoparticles were prepared by two methods: nanoprecipitation and double emulsion. The nanoparticles were characterized by their size, zeta potential and amount of DNA adsorption. Cytotoxicity tests based on mitochondrial activity (MTT test) revealed that the nanoparticles had limited cytotoxicity and that this depended on both the cell type and the nanoparticle concentration. Transgene expression was observed using the Green Fluorescence Protein gene as reporter gene, and was evaluated by flow cytometry in FaDu, MDA-MB 231 and MCF-7 cell lines. The results showed that transfection rates ranging between 4 and 7% were achieved in FaDu and MDA-MB 231 cells with nanoparticles prepared by the nanoprecipitation method. In MCF-7 cells transfected with nanoparticles prepared by either the double emulsion or the nanoprecipitation method, the transfection efficiency was between 2 and 4%. Nanoparticles prepared by nanoprecipitation were slightly more efficient than nanoparticles prepared from a double emulsion. Particle size was not an important factor for transfection, since no significant difference was observed with size between 50 and 350 nm. We showed that Eudragit RS and RL nanoparticles could introduce the transgene into different types of cells, but were generally less effective than the lipofectamine control.
Technology in cancer research & treatment 12/2009; 8(6):433-44. · 2.02 Impact Factor
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ABSTRACT: Nanoparticles loaded with two different commercial insulins (Actrapid, Novorapid and based on different blends of a biodegradable polyester (poly-epsilon-caprolactone) and a polycationic non-biodegradable acrylic polymer (Eudragit RS) were characterized in vitro. The zeta potential was positive whenever Eudragit RS was part of the nanoparticles matrix. The encapsulation efficiency was ~ 96% except for Novorapid-loaded particles of poly-epsilon-caprolactone (only 35%). In vitro release studies revealed a burst release from nanoparticles, which may be of interest for oral delivery. Novorapid-loaded nanoparticles were orally administered to diabetic rats and allowed the glycemia to be decreased when compared with free nanoparticles.
Drug Delivery 11/2009; 16(8):430-6. · 1.46 Impact Factor
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ABSTRACT: Nanoparticles (prepared from a mixture of polyester and a polycationic polymer) loaded with insulin were prepared by a double emulsion method followed by evaporation solvent. Low molecular weight heparin (LMWH) was bound by electrostatic interactions onto the surface of the particles to confer Stealth properties. These nanoparticles were characterized in vitro (mean diameter, zeta potential, encapsulation efficiency, and release kinetics) and compared with conventional (without LMWH) and unloaded nanoparticles. The pharmacokinetics of insulin were studied after intravenous injection into diabetic rats in the form of Stealth or conventional nanoparticles or as a solution. Stealth nanoparticles allowed an increase in the elimination half-life of insulin, showing that the hydrophilic layer of LMWH was able to limit recognition by the mononuclear phagocytosis system in vivo. However, complement activation studies (CH50) did not reveal significant difference between Stealth and conventional nanoparticles.
Journal of Drug Targeting 10/2009; 17(8):575-85. · 2.70 Impact Factor
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ABSTRACT: Low molecular weight heparins (LMWHs), mainly used for the prevention of deep vein thrombosis, are so far only administered by parenteral route. Presumably, due to their large size and negative charge, LMWHs are not absorbed efficiently across the mucus of the gastrointestinal tract. Since parenteral administration requires medical assistance and is not the most convenient route of application, the development of an oral dosage form of heparin would improve patients' comfort and replace vitamin K antagonists. Thus, we developed granules of two LMWHs, enoxaparin and bemiparin, based on primary granules of microcrystalline cellulose and loaded with ethylcellulose (Aquacoat ECD) or a polycationic polymer (Eudragit RS30D (ERS)) or their mixtures. The highest maximal plasma anti-Xa activities and the highest bioavailabilities for enoxaparin granules (0.45+/-0.12IU/mL; 19.00+/-0.30%, respectively) and for bemiparin granules (0.54+/-0.08IU/mL; 29.02+/-4.12%, respectively) were found after oral administration of granules loaded with ERS alone at a dose of 600IU anti-Xa/kg to rabbits. These results confirm the oral absorption of LMWH from granules loaded with polycationic polymer and open up this technology for peptides and proteins that are very sensitive to organic solvents and have poor drug absorption from the gastrointestinal tract.
International journal of pharmaceutics 07/2009; 374(1-2):12-6. · 2.96 Impact Factor
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ABSTRACT: Tinzaparin and nadroparin, two low molecular weight heparins (LMWH), were encapsulated within microparticles by the double emulsion method using ammonium methacrylate copolymer (Eudragit RS) alone or mixed with poly (d,l-lactic-co-glycolic acid) at different ratios. The resulting microparticles were characterized in vitro according to particle size, encapsulation rate and release profiles both by chemical and biological methods. The biological method was based on the measurement of the anti-Xa/anti-IIa ratio typical of each LMWH. This ratio also reflects the relative proportion between active chains below and above the critical chain length of 5000 Da (i.e. BCL and ACL chains), since LMWH are mixtures of chains with various lengths and activities. For both LMWH, high entrapment efficiencies, expressed as anti-Xa and anti-IIa activities, were obtained and amounted to anti-Xa/anti-IIa ratios close to the commercial ratio. During the in vitro release, whatever the formulation, more BCL chains were released than ACL chains: a higher (compared to commercial ratio) and stable anti-Xa/anti-IIa ratio was observed. This increase of the anti-Xa/anti-IIa ratio was influenced by the type of LMWH used and the composition of the Eudragit RS formulation. This type of microparticles could constitute a new pharmaceutical form of LMWH with a higher anti-Xa/anti-IIa ratio than commercial forms.
Journal of Controlled Release 06/2009; 139(1):8-14. · 5.73 Impact Factor
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ABSTRACT: The initial burst release is one of the major problems in the development of controlled release formulations including drug-loaded micro- and nanoparticles, especially with low molecular weight drugs. The objective of the present work was to encapsulate, by the W/O/W emulsion, polymeric nanoparticles into polymeric microparticles by using non-water soluble polymers and appropriate organic solvents for the preparation of these composite microparticles. They were characterized in vitro (encapsulation efficiency, mean diameter and release kinetics) and compared with nanoparticles and classical microparticles prepared by the same method. Poly-epsilon-caprolactone (PCL) dissolved in methylene chloride was used to make nanoparticles, whereas ethylcellulose and Eudragit RS dissolved in ethyl acetate, a non-solvent of poly-epsilon-caprolactone, were used for the preparation of microparticles. Ibuprofen and triptorelin acetate were chosen as lipophilic and hydrophilic model drugs, respectively. High entrapment efficiencies were obtained with ibuprofen whereas lower amounts of triptorelin acetate were encapsulated, mainly with formulations prepared with poly-epsilon-caprolactone and Eudragit RS used alone or blended with ethylcellulose. The burst was significantly lower with composite microparticles and may be explained by the slower diffusion of the drugs through the double polymeric wall formed by the nanoparticle matrix followed by another diffusion step through the microparticle polymeric wall.
International Journal of Pharmaceutics 12/2007; 344(1-2):53-61. · 3.35 Impact Factor
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ABSTRACT: The objective of the study was to prepare and evaluate carbamazepine-loaded enteric microparticles produced by a novel coacervation method. An aqueous polymeric stabilizer solution was added to an organic carbamazepine/Eudragit L100-55 solution. Water, which is a non-solvent for the drug and the enteric polymer, caused phase separation and the formation of coacervate droplets. These droplets hardened into microparticles upon further addition of the aqueous phase. The microparticles were characterized with respect to particle size distribution, morphology, encapsulation efficiency, yield, physical state and physical stability of the drug, wettability, in vitro release and in vivo bioavailability. Microparticles with a smooth surface and dense structure were obtained with high encapsulation efficiency (>85%) and yield (>90%). The drug was in a non-crystalline state in the matrix and physically stable for 5 months at room temperature. Under sink conditions, the drug dissolution rate from the microparticles was significantly enhanced compared to the physical mixture and to the pure drug; the release profile of the microparticles was stable after 5 months. Under non-sink conditions, an unstable supersaturated solution of carbamazepine was obtained from microparticles with the subsequent formation of needle-shaped crystals. The high surface area and good wettability of the microparticles, the non-crystalline state of the drug in the matrix and the fast dissolution rate contributed to a significantly enhanced oral bioavailability from the microparticles when compared to the physical mixture.
International Journal of Pharmaceutics 02/2007; 331(1):84-92. · 3.35 Impact Factor
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ABSTRACT: The hydrophobic cyclic undecapeptide cyclosporin A (CyA) used in the prevention of graft rejection and in the treatment of autoimmune diseases was encapsulated by nanoprecipitation within non-biodegradable polymeric nanoparticles. The effect of polymers (Eudragit RS or RL) and additives within the alcoholic phase (fatty acid esters and polyoxyethylated castor oil) on the size, zeta potential and the encapsulation efficiency of the nanoparticles was investigated. The mean diameter of the various CyA nanoparticles ranged from 170 to 310 nm. The size as well as the zeta potential increased by adding fatty acid ester and polyoxyethylated castor oil within the organic phase. No significant differences in surface potential were observed for all formulations tested. Probably due to the very low water solubility of the drug, high encapsulation efficiencies were observed in a range from 70 to 85%. The oral absorption of CyA from these polymeric nanoparticles was studied in rabbits and compared to that of Neoral capsule. Based on comparison of the area under the blood concentration-time curve values, the relative bioavailability of CyA from each nanoparticulate formulation ranged from 20 to 35%.
International Journal of Pharmaceutics 02/2005; 288(1):169-75. · 3.35 Impact Factor
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ABSTRACT: 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.
Drug Development and Industrial Pharmacy 02/2005; 31(2):179-89. · 1.49 Impact Factor
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ABSTRACT: Non-degradable microparticles based on ammonio methacrylate copolymers (Eudragit RS:RL 4:1 blends) containing the hydrophilic drug propranolol HCl and/or the lipophilic drug nifedipine were prepared with an oil-in-water (O/W) and a water-in-oil-in-water (W/O/W) solvent evaporation technique. Both drugs were successfully incorporated separately as well as simultaneously. In all cases, the resulting release rate(s) of the drug(s) was/were found to be controlled over periods of at least 8 h. To elucidate the underlying mass transport mechanisms, the microparticles were thoroughly characterized by X-ray powder diffractometry, differential scanning calorimetry, particle size analysis, and determination of the actual drug loading(s). Analytical solutions of Fick's second law of diffusion considering non-steady state conditions were used to describe the release of propranolol HCl. Interestingly, the resistance for drug release within the unstirred liquid boundary layers on the surfaces of the microparticles was found to be negligible compared to the diffusional resistance within the polymeric devices. Importantly, the mathematical theories could be used to normalize the experimentally determined in vitro drug release with respect to the microparticle size. Thus, the effect of the type of preparation method (O/W vs. W/O/W) and device composition (polymer blend plus one drug only vs. polymer blend plus drug combination) on the diffusional resistance within the microparticles could be studied. In addition, further insight into the occurring mass transport processes was gained. For example, the time-dependent evolution of the drug concentration profiles within the microparticles upon exposure to the release medium could be calculated. An interesting practical application of the mathematical theories is the possibility to predict the effect of different formulation parameters on the resulting drug release patterns, e.g. the effect of the microparticle size.
Journal of Controlled Release 04/2003; 88(3):413-28. · 5.73 Impact Factor
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ABSTRACT: The aim of the present work was to investigate the preparation of low molecular weight heparin (LMWH) nanoparticles (NP) as potential oral heparin carriers. The NP were formulated using an ultrasound probe by water-in-oil-in-water (w/o/w) emulsification and solvent evaporation with two biodegradable polymers [poly-epsilon-caprolactone, PCL and poly(D,L-lactic-co-glycolic acid) 50/50, PLGA] and two non-biodegradable positively charged polymers (Eudragit RS and RL) used alone or in combination. The mean diameter of LMWH-loaded NP ranged from 240 to 490 nm and was dependent on the reduced viscosity of the polymeric organic solution. The surface potential of LMWH NP prepared with Eudragit polymers used alone or blended with PCL and PLGA was changed dramatically from strong positive values obtained with unloaded NP to negative values. The highest encapsulation efficiencies were observed when Eudragit polymers took part in the composition of the polymeric matrix, compared with PCL and PLGA NP exhibiting low LMWH entrapment. The in vitro LMWH release in phosphate buffer from all formulations ranged from 10 to 25% and was more important (two- to threefold) when esterase was added into the dissolution medium. The in vitro biological activity of released LMWH, determined by the anti-factor Xa activity with a chromogenic substrate, was preserved after the encapsulation process, making these NP good candidates for oral administration.
Drug Development and Industrial Pharmacy 11/2002; 28(9):1091-9. · 1.49 Impact Factor
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ABSTRACT: Microparticles containing heparin were prepared by a water-in-oil-in-water emulsification and evaporation process with pure or blends of biodegradable (poly-epsilon-caprolactone and poly(D,L-lactic-co-glycolic acid)) and of positively-charged non-biodegradable (Eudragit RS and RL) polymers. The influence of polymers and some excipients (gelatin A and B, NaCl) on the particle size, the morphology, the heparin encapsulation rate as well as the in vitro drug release was investigated. The diameter of the microparticles prepared with the various polymers ranged from 80 to 130 microns and was found to increase significantly with the addition of gelatin A into the internal aqueous phase. Microparticles prepared with Eudragit RS and RL exhibited higher drug entrapment efficiency (49 and 80% respectively) but lower drug release within 24 h (17 and 3.5% respectively) than those prepared with PCL and PLAGA. The use of blends of two polymers in the organic phase was found to modify the drug entrapment as well as the heparin release kinetics compared with microparticles prepared with a single polymer. In addition, microparticles prepared with gelatin A showed higher entrapment efficiency, but a significant initial burst effect was observed during the heparin release. The in vitro biological activity of heparin released from the formulations affording a suitable drug release has been tested by measuring the anti-Xa activity by a colorimetric assay with a chromogenic substrate. The results confirmed that heparin remained unaltered after the entrapment process.
Drug Development and Industrial Pharmacy 10/2002; 28(8):1033-41. · 1.49 Impact Factor
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ABSTRACT: The use of nanoparticles for targeted oral drug delivery to the inflamed gut tissue in inflammatory bowel disease was examined. Such a strategy of local drug delivery would be a distinct improvement compared with existing colon delivery devices for this disease. An experimental colitis was induced by trinitrobenzenesulfonic acid to male Wistar rats. Rolipram, an anti-inflammatory model drug, was incorporated within poly(lactic-coglycolic acid) nanoparticles, which were administered once a day orally for five consecutive days. A clinical activity score and myeloperoxidase activity were determined to assess the inflammation, whereas an adverse effect index reflected the remaining neurotropic effect of rolipram resulting from its systemic absorption. All nanoparticle formulations proved to be as efficient as the drug in solution in mitigating the experimental colitis. The clinical activity score and myeloperoxidase activity decreased significantly after the oral administration of rolipram nanoparticles or solution. During the next 5 days when animals were kept without drug treatment the drug solution group displayed a strong relapse, whereas the nanoparticle groups continued to show reduced inflammation levels. The rolipram solution group had a high adverse effect index, whereas the rolipram nanoparticle groups proved their potential to retain the drug from systemic absorption as evidenced by a significantly reduced index. This new delivery system enabled the drug to accumulate in the inflamed tissue with higher efficiency than when given as solution. The nanoparticle deposition in the inflamed tissue should be given particular consideration in the design of new carrier systems for the treatment of inflammatory bowel disease.
Journal of Pharmacology and Experimental Therapeutics 12/2001; 299(2):775-81. · 3.83 Impact Factor
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ABSTRACT: The aim of the present work was to investigate the preparation of nanoparticles as a potential drug carrier and targeting system for the treatment of inflammatory bowel disease. Rolipram was chosen as the model drug to be incorporated within nanoparticles. Pressure homogenization-emulsification (PHE) with a microfluidizer or a modified spontaneous emulsification solvent diffusion method (SESD) were used in order to select the most appropriate preparation method. Poly(epsilon-caprolactone) has been used for all preparations. The drug loading has been optimized by varying the concentration of the drug and polymer in the organic phase, the surfactants (polyvinyl alcohol, sodium cholate) as well as the volume of the external aqueous phase. The rolipram encapsulation efficiency was high (>85%) with the PHE method in all cases, whereas with the SESD method encapsulation efficiencies were lower (<40%) when lower surfactant concentrations and reduced volume of aqueous phase were used. Release profiles were characterized by a substantial initial burst release with the PHE method (25-35%) as well as with the SESD method (70-90%). A more controlled release was obtained after 2 days of dissolution with the PHE method (70-90%), no further significant drug release was observed with the SESD method.
Journal of Controlled Release 04/2001; 71(3):297-306. · 5.73 Impact Factor
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ABSTRACT: The objective of this study was to investigate the mechanical properties (% elongation and puncture strength) of poly(D,L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) films as a function of exposure time to an aqueous medium and to correlate the mechanical properties to the degradation/erosion of the polymer as a function of the type of polymer [PLA, weight-average molecular weight (M(W)) 270,300, or PLGA 50:50, M(W) 56,500], the type of plasticizer [(triethyl citrate (TEC) or acetyltributyl citrate (ATBC)], and the exposure time to pH 7.4 phosphate buffer. The glass transition temperature of the films was measured by differential scanning calorimetry (DSC), the molecular weight by size exclusion chromatography (SEC), and the polymer erosion and hydration gravimetrically. The mechanical properties were strongly affected by the type of polymer and plasticizer. PLGA films showed a faster loss of mechanical integrity. TEC, the water-soluble plasticizer, leached from the films, resulting in major differences in the mechanical properties (flexibility) when compared with films plasticized with the more permanent, water-insoluble ATBC. A significant difference in M(W) decrease was seen between plasticizer-free and plasticizer-containing PLA films, but not for PLGA films. Plasticized PLA films, which were above their glass transition temperature in the rubbery state, showed a faster decrease in M(W) than plasticizer-free PLA ones, which were in the glassy state. The plasticizer addition to the lower M(W) PLGA did not enhance the polymer degradation; the plasticizer-free PLGA was already in the rubbery state. Major differences between the two polymers were also seen in the mass loss and the water uptake studies. After 4 weeks, the mass loss was between 2.6 and 7.0% and the water uptake between 10.1 and 21.1% for PLA films, whereas for PLGA films, the mass loss was between 40.3 and 51.3% and the water uptake between 221.9 and 350.6%. 2000 Wiley-Liss, Inc.
Journal of Pharmaceutical Sciences 01/2001; 89(12):1558-66. · 3.06 Impact Factor
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Pharmaceutical Research 10/2000; 17(9):1144-7. · 4.09 Impact Factor
