Effects of formulation parameters on encapsulation efficiency and release behavior of thienorphine loaded PLGA microspheres

To develop a long-acting injectable thienorphine biodegradable poly (d, l-lactide-co-glycolide) (PLGA) microsphere for the therapy of opioid addiction, the effects of formulation parameters on encapsulation efficiency and release behavior were studied. The thienorphine loaded PLGA microspheres were prepared by o/w solvent evaporation method and characterized by HPLC, SEM, laser particle size analysis, residual solvent content and sterility testing. The microspheres were sterilized by gamma irradiation (2.5 kGy). The results indicated that the morphology of the thienorphine PLGA microspheres presented a spherical shape with smooth surface, the particle size was distributed from 30.19?±?1.17 to 59.15?±?0.67μm and the drug encapsulation efficiency was influenced by drug/polymer ratio, homogeneous rotation speed, PVA concentration in the water phase and the polymer concentration in the oil phase. These changes were also reflected in drug release. The plasma drug concentration vs. time profiles were relatively smooth for about 25 days after injection of the thienorphine loaded PLGA microspheres to beagle dogs. In vitro and in vivo correlation was established.     

Effects of alginate coated on PLGA microspheres for delivery tetracycline hydrochloride to periodontal pockets

The effects of alginate coated on tetracycline (Tc) loaded poly (D, L-lactic-co-glycolic acid) (PLGA) microspheres fabricated by double emulsion solvent evaporation technique for local delivery to periodontal pocket were investigated. Alginate coated PLGA microspheres showed smoother surface but enlarged their particle sizes compared with those of uncoated ones. In addition, alginate coated microspheres enhanced Tc encapsulation efficiency (E.E.) from 11.5?±?0.5% of uncoated ones to 17.9?±?0.5%. Moreover, all of the coated PLGA microspheres even fabricated at different conditions could prolong Tc release from 9–12 days with 50% or higher in cumulative release of Tc compared with those of uncoated ones. The swelling ratios of PLGA microspheres for alginate coated or uncoated ones, one of the possible mechanisms for enhancing Tc release for the coated ones, were measured. The results showed that 20% or higher in swelling ratio for the coated microspheres at the earlier stage of hydration (e.g.?≤?24?h) could be an important factor to result in high Tc release compared to the uncoated ones. In conclusion, alginate coated Tc loaded PLGA microspheres could enhance Tc delivery to periodontal pocket by enhancing drug encapsulated efficiency, released quantities and sustained release period compared with uncoated ones.     

Heparin Immobilized Porous PLGA Microspheres for Angiogenic Growth Factor Delivery

Purpose Heparin immobilized porous poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres were prepared for sustained release of basic fibroblast growth factor (bFGF) to induce angiogenesis.Materials and Methods Porous PLGA microspheres having primary amine groups on the surface were prepared using an oil-in-water (O/W) single emulsion method using Pluronic F-127 as an extractable porogen. Heparin was surface immobilized via covalent conjugation. bFGF was loaded into the heparin functionalized (PLGA-heparin) microspheres by a simple dipping method. The bFGF loaded PLGA-heparin microspheres were tested for in vitro release and in vivo angiogenic activity.Results PLGA microspheres with an open-porous structure were formed. The amount of conjugated amine group onto the microspheres was 1.93 ± 0.01 nmol/mg-microspheres, while the amount of heparin was 95.8 pmol/mg-microspheres. PLGA-heparin microspheres released out bFGF in a more sustained manner with a smaller extent of initial burst than PLGA microspheres, indicating that surface immobilized heparin controlled the release rate of bFGF. Subcutaneous implantation of bFGF loaded PLGA-heparin microspheres in mice significantly induced the formation of new vascular microvessels.Conclusions PLGA microspheres with an open porous structure allowed significant amount of heparin immobilization and bFGF loading. bFGF loaded PLGA-HP microspheres showed sustained release profiles of bFGF in vitro, demonstrating reversible and specific binding of bFGF to immobilized heparin. They also induced local angiogenesis in vivo in an animal model.     

Improved bioavailability of orally delivered insulin using Eudragit-L30D coated PLGA microparticles

Large porous microparticles of PLGA entrapping insulin were prepared by solvent evaporation method and evaluated in diabetes induced rat for its efficacy in maintaining blood sugar level from a single oral dose. Incorporation of Eudragit L30D (0.03% w/v) in the external aqueous phase resulted in formation of pH responsive enteric coated polymer particles which release most of the entrapped insulin in alkaline pH. At acidic pH, release of insulin from uncoated PLGA microparticles and Eudragit L30D coated PLGA microparticles was 31.62?±?1.8% and 17.5?±?1.29%, respectively, for initial 30 min. However, in 24 h, in vitro released insulin from uncoated PLGA and Eudragit coated particles was 96.29?±?1.01% and 88.30?±?1%, respectively. Released insulin from composite polymer particles were mostly in monomer form without aggregation and was stable for a month at 37°C. Oral administration of insulin loaded PLGA (50 : 50) and Eudragit L30D coated PLGA (50 : 50) microparticles (equivalent to 25 IU insulin/kg of animal weight) in alloxan induced diabetic rats resulted in 37.3?±?11% and 62.7?±?3.8% reduction in blood glucose level, respectively, in 2 h. This effect continued up to 24 h in the case of Eudragit L30D coated PLGA microparticles. Results demonstrate that use of stabilizers during PLGA particle formulation, large porous particle for quick release of insulin and coating with Eudragit L30D resulted in a novel oral formulation for once a day delivery of insulin.     

A Heterogeneously Structured Composite Based on Poly(lactic-co-glycolic acid) Microspheres and Poly(vinyl alcohol) Hydrogel Nanoparticles for Long-Term Protein Drug Delivery

Purpose. To prepare a heterogeneously structured composite based on poly (lactic-co-glycolic acid) (PLGA) microspheres and poly(vinyl alcohol) (PVA) hydrogel nanoparticles for long-term protein drug delivery. Methods. A heterogeneously structured composite in the form of PLGA microspheres containing PVA nanoparticles was prepared and named as PLGA-PVA composite microspheres. A model protein drug, bovine serum albumin (BSA), was encapsulated in the PVA nanoparticles first. The BSA-containing PVA nanoparticles was then loaded in the PLGA microspheres by using a phase separation method. The protein-containing PLGA-PVA composite microspheres were characterized with regard to morphology, size and size distribution, BSA loading efficiency, in vitroBSA release, and BSA stability. Results. The protein-containing PLGA-PVA composite microspheres possessed spherical shape and nonporous surface. The PLGA-PVA composite microspheres had normal or Gaussian size distribution. The particle size ranged from 71.5 m to 282.7 m. The average diameter of the composite microspheres was 180 m. The PLGA-PVA composite microspheres could release the protein (BSA) for two months. The protein stability study showed that BSA was protected during the composite microsphere preparation and stabilized inside the PLGA-PVA composite microspheres. Conclusions. The protein-containing PLGA-PVA composite may be suitable for long-term protein drug delivery.     

Enhanced oral bioavailability of salmeterol by loaded PLGA microspheres: preparation,in vitro,and in vivo evaluation

The objective of the current study was to prepare microspheres of salmeterol (SM) using poly (lactide-co-glycolide) (PLGA) and assess its viability to enhance the oral bioavailability. Microspheres of SM were prepared by oil-in-water emulsion-solvent evaporation method. The formulations were characterized in encapsulation efficiency, particle size, zeta potential, and in vitro release. The prepared microspheres were found to be spherical in shape with smooth surface. The size of microspheres ranged from 14.7 to 16.5?µm. The polydispersity index (PDI) was 0.12?±?0.05 and the zeta potential was ?33.2?±?1.4?mV. In vitro release profile, SM was graduated released from the microspheres as time lapsed, suggesting that SM was well entrapped in SM-loaded PLGA microspheres. The model that fitted best for SM released from the microspheres was Higuchi equation. In vivo study, SM-loaded PLGA microspheres are thought to have the potential to maintain SM concentration within target ranges for a long time, decreasing side effects caused by concentration fluctuation, ensuring the efficiency of treatment and improving patient compliance by reducing dosing frequency.     

β-methasone-containing biodegradable poly(lactide-co-glycolide) acid microspheres for intraarticular injection: effect of formulation parameters on characteristics and in vitro release

A sustained drug release system based on the injectable poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with β-methasone was prepared for localized treatment of rheumatic arthritis. The microscopy and structure of microspheres were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR). The effects of various formulation parameters on the properties of microspheres and in vitro release pattern of β-methasone were also investigated. The results demonstrated that increase in drug/polymer ratio led to increased particle size as well as drug release rate. Increase in PLGA concentration led to increased particle size, but decreased burst release. The drug encapsulation efficiency increased sharply by increasing polyvinyl alcohol (PVA) concentration in the aqueous phase from 1.5 to 2.0%. β-methasone release rate decreased considerately with decreasing OP (organic phase)/AP (aqueous phase) volume ratio. Stirring rate had significantly influence on the particle size and encapsulation efficiency. Independent of formulation parameters, β-methasone was slowly released from the PLGA microspheres over 11 days. The drug release profile of high drug loaded microspheres agree with Higuchi equation with a release mechanism of diffusion and erosion, that of middle drug loaded microspheres best agreed with Hixcon-Crowell equation and controlled by diffusion and erosion as well. The low drug loaded microspheres well fitted to logarithm normal distribution equation with mechanism of purely Fickian diffusion.     

5-Fluorouracil-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(lactide-co-glycolide) polymers: Characterization and drug release

5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47?±?11 and 67?±?12?µg 5-FU?mg^?1 microspheres and the percentage of entrapment efficiency was between 52?±?12 and 74?±?13. Microspheres were of small size (average diameter: 0.9?±?0.4–1.4?±?0.8?µm microspheres without drug; 1.1?±?0.5–1.7?±?0.9?µm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger T_g. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of T_g of the polymer of the microspheres. The presence of 5-FU did not modify the T_g values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28–129?h) was in the order PLA?>?PLGA 75/25?>?PLGA 50/50. A burst effect (17–20%) was observed during the first hour and then a period of constant release rate (3.52?±?0.82–1.46?±?0.26?µg 5-FU?h^?1 per milligram of microspheres) up to 8 or 13?h, depending on the polymer, was obtained.     

Sustained release nanoparticulate formulation containing antioxidant-ellagic acid as potential prophylaxis system for oral administration

The aim of the present work was to develop ellagic acid (EA) loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for oral administration. PLGA nanoparticles were prepared by a method based on the concept of emulsion–diffusion–evaporation by using polyethylene glycol (PEG) 400 as a cosolvent for solubilizing the drug. While developing this method, didodecyldimethylammomium bromide (DMAB) and polyvinyl alcohol (PVA), alone and in combination with chitosan (CS) were employed. DMAB stabilized particles were the smallest of all the formulations with a particle size of 148.5 nm. PVA alone gave particles of 269.7 nm but a blend with CS (80:20) resulted in an increase in particle size (359.6 ± 23.6 nm). Initial release of EA from nanoparticles in pH 7.4 phosphate buffer was rapid, followed by a slower sustained release. Release rates followed the order PVA > PVA–CS > DMAB. Release rate from the PLGA–DMAB particles was slowest, which is attributed to higher hydrophobicity of DMAB as compared to PVA, preventing diffusion of drug out of polymeric matrix. Insolubility of CS at alkaline pH could have retarded the release in case of PVA–CS system. In situ intestinal permeability study of pure drug and the drug encapsulated in nanoparticles prepared using PVA, PVA–CS blend and DMAB as stabilizer in rats showed 66, 75, 73 and 87% permeation, respectively. EA showed good free radical scavenging effect in a yeast cell culture model as well as in a cell free system.     

Release optimization of epidermal growth factor from PLGA microparticles

Abstract

The objective of this study was to prepare poly lactic-co-glycolic acid (PLGA)-based microparticles as potential carriers for recombinant human epidermal growth factor (rhEGF). In order to optimize characteristic parameters of protein-loaded microspheres, bovine serum albumin (BSA) was selected as the model protein. To reduce burst release as a common problem of microspheres, a proper alteration in the particle composition was used, such as addition of poly vinyl alcohol and changes in initial drug loading. The effects of these parameters on particle size, encapsulation efficiency and in vitro release kinetics of BSA in PLGA microspheres were investigated using a Box–Behnken response surface methodology. The biological activity of the released rhEGF was assessed using human skin fibroblasts cell proliferation assay. The prepared rhEGF-loaded microspheres had an average size of 6.44?±?2.45?µm, encapsulation efficiency of 97.04?±?1.13%, burst release of 13.06?±?1.35% and cumulative release of 22.56?±?2.41%. The proliferation of human skin fibroblast cells cultivated with rhEGF releasate of microspheres was similar to that of pure rhEGF, indicating the biological activity of released protein confirming the stability of rhEGF during microsphere preparation. These results are in agreement with the purpose of our study to prepare rhEGF-entrapped PLGA microparticles with optimized characteristics.     

Preparation and characterization of poly(D,L-lactic-co-glycolic Acid) microspheres containing flurbiprofen sodium

This study aimed to prepare biodegradable microspheres containing flurbiprofen sodium, a nonsteroidal anti-inflammatory drug (NSAID), as the drug delivery system to the periodontal pocket. Microspheres were prepared from biodegradable copolymers of poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation method. The effects of the different copolymers and amounts of polyvinyl alcohol (PVA) as a dispersing agent on characteristics of the microspheres were evaluated. Although there was no correlation between microsphere size and amount of PVA, an optimum PVA concentration was essential to achieve narrower size distributions of microspheres. As the concentration of PVA increased, the drug loading of the microspheres increased. The effect of PVA on drug loading was found to be statistically significant for those microspheres prepared from PLGA 50:50 (p < 0.05). Regarding copolymer composition, PLGA 85:15 provided higher drug loading into the microspheres than PLGA 50:50 (p < 0.05). The recoveries of microspheres (60-80%) were affected neither by different PVA concentrations nor by copolymer compositions (p > 0.05). According to the first-order release rate constants of the microspheres, the microspheres of PLGA 50:50 released the drug at the highest rate consistently, with the highest hydrophilicity of this copolymer.     

In vitro characterization of methotrexate loaded poly(lactic-co-glycolic) acid microspheres and antitumor efficacy in Sarcoma-180 mice bearing tumor

Methotrexate (MTX) loaded poly (lactic-co-glycolic) acid (PLGA) microspheres were prepared by emulsion solvent evaporation technique. The mean diameter of the microspheres was affected by the type of emulsion stabilizer, polymer concentration, aqueous and organic phase volume and stirring speed. The in vitro release was triphasic and was dependent on copolymer composition and molecular weight of the polymer. Antitumor efficacy in Sarcoma-180 tumor bearing mice exhibited increased volume doubling time (18 ± 2.7 days) compared to plain subcutaneous injection of methotrexate (8 ± 0.7 days). Preliminary pharmacokinetic studies following subcutaneous administration of MTX loaded PLGA microspheres illustrated the controlled release of the drug. The studies demonstrated the feasibility of employing PLGA as an effective carrier for antineoplastic drug like methotrexate.     

Sodium fusidate-poly(D,L-lactide-co-glycolide) microspheres: Preparation,characterisation and in vivo evaluation of their effectiveness in the treatment of chronic osteomyelitis

Purpose: The aim of this study was to prepare poly(D,L-lactide-co-glycolide) (PLGA) microspheres containing sodium fusidate (SF) using a double emulsion solvent evaporation method with varying polymer:drug ratios (1:1, 2.5:1, 5:1) and to evaluate its efficiency for the local treatment of chronic osteomyelitis.

Methods: The particle size and distribution, morphological characteristics, thermal behaviour, drug content, encapsulation efficiency and in vitro release assessments of the formulations had been carried out. Sterilized SF-PLGA microspheres were implanted in the proximal tibia of rats with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. After 3 weeks of treatment, bone samples were analysed with a microbiological assay.

Results: PLGA microspheres between the size ranges of 2.16–4.12?µm were obtained. Production yield of all formulations was found to be higher than 79% and encapsulation efficiencies of 19.8–34.3% were obtained. DSC thermogram showed that the SF was in an amorphous state in the microspheres and the glass transition temperature (T_g) of PLGA was not influenced by the preparation procedure. In vitro drug release studies had indicated that these microspheres had significant burst release and their drug release rates were decreased upon increasing the polymer:drug ratio (p?<?0.05). Based on the in vivo data, rats implanted with SF-PLGA microspheres and empty microspheres showed 1987?±?1196 and 55526?±?49086 colony forming unit of MRSA in 1?g bone samples (CFU/g), respectively (p?<?0.01).

Conclusion: The in vitro and in vivo studies had shown that the implanted SF loaded microspheres were found to be effective for the treatment of chronic osteomyelitis in an animal experimental model. Hence, these microspheres may be potentially useful in the clinical setting.     

白藜芦醇PLGA长效注射微球的制备及工艺考察

目的采用乳化溶剂挥发法制备白藜芦醇聚乳酸羟基乙酸[poly(lactic-co-glycolic acid),PL-GA]长效微球,评价各因素对微球性质的影响。方法以微球的包封率、载药量、突释和粒径作为微球的质量评价指标,研究分散相与连续相的体积比、PLGA浓度、聚乙烯醇(polyvinyl alcohol,PVA)浓度、搅拌速度对微球性质的影响,并优化白藜芦醇PLGA微球的制备工艺。结果分散相与连续相的体积比为1∶50时,包封率高,但4 h突释量达到76%,当分散相与连续相体积比由1∶50提升到1∶150时,突释降低了22%;随着聚合物浓度的增加粒径明显增大,突释显著降低;理论载药量对粒径影响不大,在高载药量时突释显著减少;搅拌速度的增加使粒径减小,突释增加;PVA浓度的增加对粒径没有明显的影响,但当PVA的质量浓度从1 g.L-1增加到5 g.L-1时,包封率从93.57%降低到80.31%。结论分散相与连续相的体积比、PLGA浓度、PVA浓度、搅拌速度对微球性质有很大的影响。优化条件下制备的微球形态完整,载药量为(27.86±1.00)%,包封率为(93.57±2.87)%,平均粒径约为21.12μm。白藜芦醇PLGA微球体外释放25 d的累积释药率达(94.04±4.94)%,有望研制成1个月给药1次的给药系统。     

Preparation and Characterization of Poly (D,L-Lactide-Co-Glycolide) Microspheres for Controlled Release of Poly(L-Lysine) Complexed Plasmid DNA

Purpose. To produce and characterize controlled release formulations of plasmid DNA (pDNA) loaded in poly (D,L-lactide-co-glycolide) (PLGA) microspheres both in free form and as a complex with poly (L-lysine). Methods. Poly (L-lysine) (PLL) was used to form pDNA/PLL complexes with complexation ratio of 1:0.125 and 1:0.333 w/w to enhance the stability of pDNA during microsphere preparation and protect pDNA from nuclease attack. pDNA structure, particle size, zeta potential, drug loading, in vitro release properties, and protection from DNase I were studied. Results. The microspheres were found to be spherical with average particle size of 3.1-3.5 m. Drug loading of 0.6% was targeted. Incorporation efficiencies of 35.1% and 29.4-30.6% were obtained for pDNA and pDNA/PLL loaded microspheres respectively. Overall, pDNA release kinetics following the initial burst did not correlate with blank microsphere polymer degradation profile suggesting that pDNA release is convective diffusion controlled. The percentage of supercoiled pDNA in the pDNA and pDNA/PLL loaded microspheres was 16.6 % and 76.7-85.6% respectively. Unencapsulated pDNA and pDNA/PLL degraded completely within 30 minutes upon the addition of DNase I. Encapsulation of DNA/PLL in PLGA microspheres protected pDNA from enzymatic degradation. Conclusions. The results show that using a novel process, pDNA can be stabilized and encapsulated in PLGA microspheres to protect pDNA from enzymatic degradation.     

A novel approach to stabilization of protein drugs in poly(lactic-co-glycolic acid) microspheres using agarose hydrogel

A novel approach has been taken to stabilize protein drugs in poly(lactic-co-glycolic acid) (PLGA) microspheres. This approach creates a new protein drug delivery system, which is based on the combination of agarose hydrogel particles and PLGA microspheres. This combination produces a heterogeneously structured polymeric composite. The protein drug molecules are encapsulated in the agarose hydrogel particles and the drug-containing agarose hydrogel particles are further dispersed in the PLGA microspheres. One PLGA microsphere may contain many agarose hydrogel particles to form a PLGA–agarose composite microsphere. The PLGA–agarose composite microspheres have spherical shape and a smooth surface. They possess a normal or Gaussian size distribution and an average diameter of 150 μm. The PLGA–agarose composite microspheres have higher protein loading efficiency than that of the conventional PLGA microspheres. The hydration of the PLGA–agarose composite microsphere matrix is faster than that of the conventional PLGA microspheres. Protein drugs can be slowly released from the PLGA–agarose composite microspheres. The agarose hydrogel particles can stabilize protein drugs in the PLGA matrix, which is the major advantage of this novel protein drug delivery system over the conventional PLGA microspheres.     

Preparation and testing of cefquinome-loaded poly lactic-co-glycolic acid microspheres for lung targeting

The aim of this study was to prepare cefquinome-loaded poly lactic-co-glycolic acid (PLGA) microspheres and to evaluate their in vitro and in vivo characteristics. Microspheres were prepared using a spry drier and were characterized in terms of morphology, size, drug-loading coefficient, encapsulation ratio and in vitro release. The prepared microspheres were spherical with smooth surfaces and uniform size (12.4?±?1.2?μm). The encapsulation efficiency and drug loading of cefquinome was 91.6?±?2.6 and 18.3?±?1.3%, respectively. In vitro release of cefquinome from the microspheres was sustained for 36?h. In vivo studies identified the lung as the target tissue and the region of maximum cefquinome release. A partial lung inflammation was observed but disappeared spontaneously as the microspheres were removed through in vivo decay. The sustained cefquinome release from the microspheres revealed its applicability as a drug delivery system that minimized exposure to healthy tissues while increasing the accumulation of therapeutic drug at the target site. These results indicated that the spray-drying method of loading cefquinome into PLGA microspheres is a straightforward method for lung targeting in animals.     

Compressed biodegradable matrices of spray-dried PLGA microspheres for the modified release of ketoprofen

A spray-drying technique was used to prepare poly(lactide-co-glycolide) (PLGA) drug loaded microspheres. Ketoprofen was chosen as a model NSAID drug. The microspheres were characterized in terms of morphology, drug content and release behaviour. The spray-dried particles were subject to a direct compression process for the preparation of biodegradable matrix tablets. The spray-dried powders were found to have good compaction properties. Tablets were also prepared from a mixture of microspheres and microcrystalline cellulose, mannitol and hydroxypropylmethylcellulose or sodium alginate. The release of ketoprofen in phosphate buffer (pH 7.4) was significantly sustained, indicating the suitability of using tabletted spray-dried PLGA microspheres for controlled drug delivery. The results show that spray-dried PLGA particles have promising properties as direct compression and release controlling excipients in matrix tablets for oral administration.     

Evaluation of enzyme stability during preparation of polylactide-co-glycolide microspheres

This work was aimed at studying enzyme prolidase stability and its interactions with the reagents and the process conditions involved in preparation, by an emulsification process, of prolidase loaded poly(lactide-co-glycolide) (PLGA) microparticulate systems. Enzyme stability was tested with respect to contact with methylene chloride, ethyl acetate, PLGA polymers, and several agents used as emulsifiers such as polyvinyl alcohol (PVA), polyvinyl pyrolidone (PVP), carboxymethyl cellulose (CMC) and sodium oleate (NaOl). Enzyme stability to temperature and mechanical stirring was also evaluated. Prolidase-loaded PLGA microspheres were prepared and evaluated in terms of protein activity. The results obtained showed that the prolidase-loaded PLGA microspheres can be prepared only upon eyzyme stabilization by addition of both BSA and MnCl 2 into its TRIS solution. Methylene chloride was the suitable organic solvent to be used in the double emulsion process, together with PVA as dispersing agent in the outer aqueous phase. Low temperatures during the emulsification step and very short process times are recommended, in order to maintain enzyme activity at its maximum. In these conditions spherical microspheres were obtained, releasing active prolidase for up to 15 days.     

Influence of drying processes on the structures,morphology and in vitro release profiles of risperidone-loaded PLGA microspheres

The purpose of this study was to investigate the influences of drying methods on the risperidone (RIS) release profiles of RIS-loaded PLGA microspheres. These microspheres were fabricated with an O/W emulsion solvent evaporation method. The wet microspheres were dried with freeze drying and vacuum drying methods. The microspheres were mono-dispersed spheres with an average diameter of 100?μm. Studies found that drying methods had great influence on the porosity, morphology, and release profiles of RIS-loaded PLGA microspheres. Specifically, the freeze-dried microspheres had higher porosity (78.46?±?1.64%) than those vacuum-dried ones (52.45?±?2.68%), and they showed higher RIS release rates (p?<?0.05). In the accelerated release tests (45?°C), these microspheres dried under the pressures of 700?mmHg and 200?mmHg gave faster release rates than those ones dried under the pressure of 450?mmHg. Importantly, the accelerated release test (45?°C) had a high correlation with the real-time test (37?°C) (R²?>?0.99). These studies exhibited a significance in the precise preparation of RIS-loaded PLGA microspheres.