Particle Size Of Microspheres Research Articles

Synchronic release of two hormonal contraceptives for about one month from the PLGA microspheres: In vitro and in vivo studies

A controlled drug release system based on the injectable PLGA microspheres loaded with gestodene and ethinyl estradiol was prepared and evaluated for the feasibility of monthly synchronic delivery of the two hormonal contraceptives. The scanning electron microscopy, light-scattering analyzer and gel permeation chromatography were used to study the morphology, particle size and molecular weight of the polymer microspheres, respectively. HPLC was utilized to determine the drug loading and the drug released, while a LC-MS-MS system was employed to analyze the plasma drug concentration. Result indicated that the PLGA particles obtained were spherical and appropriate in size. The formulation was stable during the test period. In vitro drug release from the microspheres for both drugs was sustained for about 30 days mostly by the diffusion mechanism. The plasma drug concentration-time profiles of the drug-loaded microspheres were relatively smooth after subcutaneous injection to rats for about 1-month, compared with that for drug suspension. In vitro and in vivo correlation was established. One of the most important facts is the synchronicity of the two contraceptives both in the release kinetics in vitro and the pharmacokinetic behaviors in vivo. Therefore, the synchronic delivery of two contraceptives is achieved for about 1 month by using the injectable PLGA-based microspheres.

Controlled Synthesis of Optically Active Polyaniline Nanorods and Nanostructured Gold Microspheres Using Tetrachloroaurate as an Efficient Oxidant of Aniline

Optically active polyaniline nanorods and hierarchically structured gold microspheres are synthesized using tetrachloroaurate as an efficient oxidant of aniline in the presence of a chiral inducing agent camphorsulfonic acid. The chiral organization of the resultant polyaniline nanorods is strongly affected by the ratio of aniline to AuCl4−, with the highest optical activity being observed for the ratio around 5:2. The particle size and size distributions of the gold microspheres are influenced by the concentration of the oxidant tetrachloroaurate.

Characterization Of Glipizide-Loaded Polymethacrylate Microspheres Prepared By An Emulsion Solvent Evaporation Method

Purpose: The purpose of the present investigation was to formulate and evaluate microencapsulated glipizide produced by the emulsion – solvent evaporation method, Method: Microspheres were prepared using polymethacrylate polymers (Eudragit® RS 100 and RL 100) by solvent evaporation method and characterized for their micromeritic properties and drug loading, as well as by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy. In vitro release studies were performed in phosphate buffer (pH 7.4). Result: The resulting microspheres obtained by solvent evaporation method were white and free flowing in nature. The mean particle size of microspheres ranged from 420 - 660 μm and the encapsulation efficiencies ranged from 40.27 - 86.67 %. The encapsulation efficiency was also found to be dependant on nature of polymer used in the formulation. The infrared spectra confirmed the stable character of glipizide in the drug-loaded microspheres. Scanning electron microscopy revealed that the microspheres were spherical in nature. From the in vitro drug dissolution studies it was found that the sustaining effect of microspheres depended on the polymer concentration, amount of dispersant used and the type of polymer used in the formulation. The mechanism of drug release from the microspheres was found to be non-Fickian type. Conclusion: Eudragit® microspheres containing glipizide could be prepared successfully by using an emulsion solvent evaporation technique using polymethacrylate polymers, which will not only sustain the release of drug but also manage the complicacy of the diabetes in a better manner. Keywords: glipizide, Eudragit®, microspheres, controlled release, polymethacrylate.Tropical Journal of Pharmaceutical Research Vol. 7 (1) 2008: pp. 879-885

Application of a Novel Approach to Prepare Biodegradable Polylactic-co-glycolic Acid Microspheres: Surface Liquid Spraying

A novel approach which had foreground of industrialization, surface liquid spraying, was studied in this paper to prepare biodegradable polylactic-co-glycolic acid (PLGA) microspheres for controlled release drug delivery system. To compare with the normal methods, the microspheres prepared by this approach were characterized by particle size distribution and photograph of microscope. The relationship between the particle size and the instrument parameters of novel method was set up for the first time. The central composite design (CCD) was applied to study the main effects and interactions of three instrument factors on preparation of microspheres. The particle size of microspheres was below 200 mum and the shape of microspheres was spherical in nature evidenced by microscope photographs. Vinpocetine was used as the model drug to prepare the vinpocetine PLGA microspheres (VIN-PLGA-MS), and then drug loading, entrapment efficiency, scanning electron microscopy (SEM), Differential Scanning Calorimetry (DSC) and in vitro drug release behavior were examined. The results indicated that the drug loading and entrapment efficiency were increased using the novel method. The drug released slowly more than 30 days. The release behavior was fit for four kinds of kinetic model. The result indicated that release behavior was fitted by Zero-order kinetic model before release 72 hours, and was fitted with First-order kinetic model after release 72 hours. The novel method developed in our paper can give a promising way for industrialization, and the foreground was also proved by the scale-up batch experiment.

Synthesis of raspberry-like magnetic polystyrene microspheres

Raspberry-like magnetic polystyrene microspheres were prepared via soap-free emulsion polymerization using 2,2′-azobis(2-methylpropionamidine) dihydrochloride (V50) as initiator. The effect of polymerization parameters, such as initiator type, initiator content and the feeding sequence on the particle size and morphology of magnetic polystyrene microspheres, were examined. The final magnetic polystyrene microspheres were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), vibrating sample magnetometer (VSM) and thermogravimetric analysis (TGA). The experimental results showed that V50 was a suitable initiator for preparation of raspberry-like magnetic polystyrene microspheres.

Poly(Lactic-co-glycolic Acid) Microspheres for the Controlled Release of Huperzine A: In Vitro and in Vivo Studies and the Application in the Treatment of the Impaired Memory of Mice

Huperzine A loaded poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared by an oil/water (o/w) solvent evaporation technique. With a decrease of the ratio of o/w from 1 : 100 to 1 : 50, the encapsulation efficiency was reduced about 4%. Increasing the PVA concentration from 0.5 to 2% reduced the percentage encapsulation efficiency of huperzine A from 60.7 to 47.4% and the particle size of microspheres from 84.2 to 26.2 microm. The addition of stearic acid improved the encapsulation efficiency, but also accelerated the in vitro release of hupezine A from microspheres. After i.m. administration of huperzine A loaded microspheres in mice, huperzine A was sustained released from the PLGA microspheres up to 12 d with a low initial burst. Passive avoidance test of mice showed that the microspheres formulation offered an improved therapeutic efficiency in the treatment of the impaired memory of the mice superior to injection gastric (i.g.) administration of huperzine A suspension at the same dose, whose therapeutic efficiency was similar as that of a 50% reduced dose of the microspheres formulation.

Development and characterization of floating microballoons for oral delivery of cinnarizine by a factorial design

Cinnarizine (CN) is a pipperazine derivative with anti-histaminic activity and high affinity to H1 receptors. The objective of this study was to produce floating microspheres (FM) of CN by diffusion solvent evaporation technique to increase drug solubility and hence its bioavailability. The effect of process variables such as: Eudragit type, stirring rate and time of stirring after addition of oily phase to the aqueous phase were evaluated on the yield, particle size, loading, release and floating behaviors of microspheres using a factorial design. Release of CN from microspheres was studied in pHs: 1.2 and 7.2 using paddle technique. The samples of dissolution test were analysed spectrophotometrically at 256.1 nm and 256.5 nm respectively. particle size of microspheres was studied using microscopic method and their floating behavior was studied in HCl (0.1 N, pH 1.2) medium with Tween 20 (0.5% w/v). Eight formulations were produced by changing 3 variables each at 2 levels: Eudragit S100 (Ps) or a combination of two Eudragits S100:RLPO (1:3) (PSR), stirring rate of 200 (R2) or 300 rpm (R3) and stirring time after addition of oily phase to the aqueous phase 0 (T0) or 1 hr (T1). The average size of microspheres was 300 µm. The highest yield efficiency (94%) was seen in PSRR3T0 formulation and the greatest loading percentage was 8.5% in PSRR2T1 formulation. The microspheres containing just Eudragit S100, didn't show suitable releasing profile during 8 hours in pH 1.2 but those containing combination of Eudragit S100:RL released approximately whole amount of CN during 10 hours (8 hours in pH 1.2 and 2 hours in pH 7.2). The highest floating percentage up to 6 hours was 77.5% in PSR2T1 formulation. The type of Eudragit used seems to play an important role in producing sustained release floating microspheres. PSRR3T0 formulation containing both types of Eudragit S100:RL (1.3) that releases 99.1% of the drug after 10 hours and 65% floating after 6 hr seems suitable for oral sustained delivery of CN.

The preparation of regenerated silk fibroin microspheres.

The objective of the present study is to investigate the possibility of preparing pure protein microspheres from regenerated silk fibroin (RSF). It is found that RSF microspheres, with predictable and controllable sizes ranging from 0.2 to 1.5 µm, can be prepared mild self-assembling of silk fibroin molecular chains. The merits of this novel method include a rather simple production apparatus and no potentially toxic agents, such as surfactants, initiators, cross-linking agents, The results show that the particle size and size distribution of RSF microspheres are greatly affected by the amount of ethanol additive, the freezing temperature and the concentration of silk fibroin. Finally, the mechanism of RSF microspheres formation is also discussed based on our experimental results.

Mucoadhesive microspheres of propranolol hydrochloride for nasal delivery

Gelatin A microspheres of propranolol hydrochloride for intranasal systemic delivery were developed with the aim to avoid first pass metabolism, to improve the patient compliance, to use an alternative therapy to conventional dosage form, to achieve controlled blood level profiles, and to improve the therapeutic efficacy of propranolol hydrochloride in the treatment of various cardiovascular disorders and as a prophylactic for migraine. Gelatin A microspheres were prepared by emulsion crosslinking method using glutaradehyde as a crosslinking agent. Gelatin and chitosan were used as polymer and co polymer respectively. All the prepared microspheres were evaluated for physical characteristics, such as particle size, incorporation efficiency, swelling index, in vitro bioadhesion using rat jejunum and in vitro drug release in pH 6.6 phosphate buffer. Average particle size of microspheres was found to be in the size range 1-50 mm. Increase in drug and polymer concentration in the formulation increased incorporation efficiency. All the microsphers showed good bioadhesive properties and swelling indices and good sustained release of drug. The data indicates that propranolol hydrochloride release followed Higuchi's matrix and Peppa's model. Stability studies showed stability of formulation at all the conditions to which they were subjected.

Synthesis and Characterization of Magnetic Polymer Microspheres

In this study, amino group–modified magnetic polymer microspheres were synthesized in a well‐shaped spherical form with a size range of 0.6 μm to 0.8 μm by mini‐emulsion polymerization. The morphology, composition, and thermal properties of the magnetic polymer microspheres were characterized by infrared (IR) spectra, transmission electron microscopy (TEM) photographs, particle size analysis, and thermogravimetric analysis (TGA) spectra. The results demonstrate that acrylic acid used for stabilizing the reaction system greatly affects the particle size, magnetite contents, and thermal stability of magnetic polymer microspheres.

Preparation of porous carbon microspheres

AbstractPorous carbon microspheres with good morphology, high yield, and controllable particle size were prepared from phenolic resin. The particle size and pore structure of the carbon microspheres were mainly inherited from their precursors, resol microspheres, which were made through curing emulsified resol in water at 120°C under saturated pressure. The average particle size and specific surface area of the porous carbon microspheres was related to the concentration of resol and polyvinyl alcohol along with the heating program. The carbonization yield to 700°C was 55 wt %. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 798–803, 2006

Drug Release Kinetics of Spray-Dried Chitosan Microspheres

The aim of this article was to investigate the drug release kinetics of spray-dried chitosan microspheres using various kinetic models. The mean particle size and encapsulation efficiency of cross-linked chitosan microspheres was between 3.8 and 4.2 μm and 96.3 and 98.7%, respectively. Spray-dried chitosan microspheres were spherical in shape with smooth surface. The surface morphology of spray-dried chitosan microspheres was affected by the crystallinity of the loaded drug and cross-linking agent. The release data of the spray-dried chitosan microspheres were treated with zero-order, first-order, Higuchi, Korsmeyer, and Kopcha kinetic models and best fit was observed with Higuchi model, indicating the release of drug from spray-dried chitosan microspheres followed Fick's law of diffusion.

Pharmacokinetics and in vitro and in vivo correlation of huperzine A loaded poly(lactic-co-glycolic acid) microspheres in dogs

The purpose of this study was to investigate the pharmacokinetics and in vitro/ in vivo correlation (IVIVC) of huperzine A loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in dogs. Several huperzine A loaded PLGA microspheres were prepared by an O/W method and three of them (single dose) were injected intramuscularly (i.m.) or subcutaneously (s.c.) to five beagle dogs, respectively. With the increase of the molecular weight of PLGA and the particle size of microspheres, the in vitro and in vivo release periods of huperzine A were prolonged. After s.c. injection, the release of huperzine A from microspheres was faster than that after i.m. injection. The IVIVC models of huperzine A loaded PLGA microspheres were established successfully and after i.m. administration the linear relationship between the in vitro and the in vivo releases was better than that after s.c. administration. It was also found when the particle size of the microspheres was smaller; the values of correlation coefficient were higher.

Preparation, characterization and in vitro drug release properties of polytrimethylene carbonate/polyadipic anhydride blend microspheres

AbstractPolyadipic anhydride (PAA), an aliphatic polyanhydride, and polytrimethylene carbonate (PTMC), an aliphatic polycarbonate, were synthesized via ring opening polymerization of oxepan‐2,7‐dione and melt‐condensation of trimethylene carbonate (1,3 dioxan‐2‐one), respectively. PTMC–PAA blend microspheres containing different ratios of buprenorphine HCl (2, 5, and 10%) were prepared by an oil‐in‐oil emulsion solvent removal method. Microspheres with different ratios of PTMC–PAA (85/15, 70/30, and 55/45) containing 5% buprenorphine HCl were prepared. Microspheres were spherical with visible cracks and pores on the surface. The average particle size of microspheres was around 200 μm for all microspheres. Drug loading efficiency of PTMC–PAA microspheres (85/15, 70/30, and 55/45) was 97.2, 95.2, and 70.2%, respectively. With the increase in the PTMC ratio, the melting point and the enthalpy of melting were both decreased. The mechanism for drug release from PTMC–PAA blend microspheres were generally a combination of drug diffusion through polymers and biodegradation of the polymers. In first three days, the release from microspheres followed zero order kinetics and was dependent on the PAA content. After three days the drug release from microspheres followed first order kinetics. In conclusion it was demonstrated that buprenorphine HCl release from microspheres could be successfully controlled by using different ratios of PTMC–PAA blends. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2377–2383, 2006

Characterization of biodegradable chitosan microspheres containing vancomycin and treatment of experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus with prepared microspheres

The biodegradable chitosan microspheres containing vancomycin hydrochloride (VANCO) were prepared by spray drying method with different polymer:drug ratios (1:1, 2:1, 3:1 and 4:1). Thermal behaviour, particle size and distribution, morphological characteristics, drug content, encapsulation efficiency, in vitro release assessments of formulations have been carried out to obtain suitable formulation which shows sustained-release effect when implanted. Sterilized VANCO loaded microspheres were implanted to proximal tibia of rats with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. Intramuscular (IM) injection of VANCO for 21 days was applied to another group for comparison. After 3 weeks of treatment, bone samples were analysed with a microbiological assay. According to the results, encapsulation efficiency and yield of microspheres in all formulations were higher than 98% and 47%, respectively. Particle sizes of microspheres were smaller than 6 μm. All microsphere formulations have shown sustained-release effect. In vitro drug release rate decreased due to the increase in polymer:drug ratio but no significant difference was seen between these results ( p > 0.05). Based on our in vivo data, rats implanted VANCO-loaded chitosan microspheres and administered IM injection showed 3354 ± 3366 and 52500 ± 25635 colony forming unit of MRSA in 1 g bone samples (CFU/g), respectively. As a result, implanted VANCO-loaded microspheres were found to be more effective than IM route for the treatment of experimental osteomyelitis.

Influence of aluminum tristearate and sucrose stearate as the dispersing agents on physical properties and release characteristics of Eudragit RS microspheres.

The purpose of this research was to investigate the effects of different concentrations of polymer and sucrose stearate, aluminum tristearate as dispersing agents on microsphere properties and performance. The yield values of microspheres were over the 78%, and the encapsulation efficiencies were found to be ∼735. Particle sizes of microspheres prepared with aluminum tristearate were between 76 and 448 μm, while that of the microspheres containing sucrose stearate were between 521 and 2000 μm. Morphological and physicochemical properties of microspheres were investigated by scanning electron micrography and differential scanning calorimetry (DSC). DSC analysis indicated that verapamil hydrochloride formed a solid solution with acrylic polymers. In vitro release studies were performed using the flow-through cell method. While ∼80% of drug was released from the microspheres containing aluminum tristearate in 480 minutes, the same amount of drug was released from microspheres containing sucrose stearate in only 60 minutes. Chemical structures and concentrations of the dispersing agents were clearly effective on the physical properties of microspheres and their drug-release characteristics.

Preparation of micron‐size monodispersed PS/P(St/MAA) microspheres by seeded dispersion polymerization

AbstractUniform polystyrene (PSt) particles with the size of 1.9 μm were first prepared via dispersion polymerization, and then used as the seeds in a second‐stage dispersion copolymerization of styrene (St) and methacrylic acid (MAA) to produce carboxyl‐carrying microspheres. The PSt seed particles were swollen by monomer mixture of St and MAA, including an oil‐soluble initiator 2,2′‐azobisiso‐butyronitrile (AIBN), before polymerization. Finally, uniform PS/P(St/MAA) (polydispersity index, PDI = 1.02) microspheres with the size of 2.2 μm were obtained. The average particle size and size distribution of the final microspheres were investigated. MAA contents between 54 and 97 mg/g were detected from the PS/P(St/MAA) particles produced under different conditions. Dispersion medium has great influence on the kinetics of polymerization, due to its effect on the partitioning of monomers, solvents, and initiator in the particle phase, probably as well as on the conformation of the dispersion agent on the surface of the particles. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 99: 3586–3591, 2006

Preparation of microspheres with silicone oil cores and poly(N-isopropylacrylamide) shells by physical coating

Surfactant-free thermoresponsive microspheres with a silicone oil cores surrounded by poly(N-isopropylacrylamide) shells have been successfully prepared by physical coating method for the first time. The influences of reaction temperature, N-isopropylacrylamide (NIPAM) dosage, and stirring rate on the formation, morphology, particle size, and monodispersity of microspheres were experimentally studied. In the preparation of microspheres, when reaction temperature was above the lower critical solution temperature of poly(N-isopropylacrylamide), products had higher yield of particles and narrower size distribution. With increasing NIPAM dosage, the particle diameter became larger and the shell layer thickened and the monodispersity became better. With increasing stirring rate, the particle diameter and the monodispersity decreased obviously. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102:5571–5576, 2006

Characteristics of vitamin C encapsulated tripolyphosphate-chitosan microspheres as affected by chitosan molecular weight

In this paper, the effect of chitosan molecular weight on the characteristics (size, encapsulation efficiency, zeta potential, surface morphology and release rate) of vitamin C encapsulated tripolyphosphate cross-linked chitosan (TPP-chitosan) microspheres. The molecular weight of chitosan had a noticeable influence on the size, encapsulation efficiency, zeta potential, surface morphology and controlled release behaviour of the vitamin C encapsulated TPP-chitosan microspheres. The mean particle size and encapsulation efficiencies of TPP-chitosan microspheres were 3.1, 4.9 and 6.7 µm and 67.25, 60.43 and 52.74% for the microspheres prepared using low, medium and high molecular weight chitosan, respectively. All the TPP-chitosan microspheres (low, medium and high molecular weight) had positive charge on their surface. The zeta potential of the TPP-chitosan microspheres prepared using low, medium and high molecular weight chitosan was 41.25, 40.84 and 39.13 mV, respectively. The particle sizes of TPP-chitosan microspheres increased with increases in chitosan molecular weight. Molecular weight of chitosan did not affect significantly the % yield of TPP-chitosan microspheres prepared by spray-drying. The influence of chitosan molecular weight on the surface morphology of vitamin C encapsulated TPP-chitosan microspheres was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It was observed that, as the molecular weight of chitosan increases, TPP-chitosan microspheres with uniform spherical shape could be obtained. The physical state of vitamin C (amorphous or crystalline) in TPP-chitosan matrix was studied by X-ray diffraction (XRD) and it was found that vitamin C is dispersed at the molecular level (amorphous) in the TPP-chitosan matrix. Release rate of the vitamin C from TPP-chitosan microspheres was significantly affected by the chitosan molecular weight. The release rate decreased with increase in the chitosan molecular weight. The release of vitamin C from TPP-chitosan microspheres followed Fick's law of diffusion.

Effects of reaction temperature and reaction time on positive thermosensitivity of microspheres with poly(acrylamide)/poly(acrylic acid) IPN shells

We have successfully prepared monodispersed positively thermoresponsive core-shell hydrogel microspheres with poly(acrylamide- co-styrene) [P(AAM- co-St)] cores and IPN(interpenetrating polymer network)-based shells composed of poly(acrylamide)/poly(acrylic acid). The submicron-sized monodispersed P(AAM- co-St) core seeds were prepared by using a surfactant-free emulsion polymerization method, and the IPN-based shell layers were fabricated onto the core seeds by using a method of sequential IPN synthesis. Effects of reaction time and reaction temperature during preparation of IPN on the particle size, monodispersity, and thermoresponsive characteristics of microspheres were investigated. The results show that the sizes of particles with IPN shell layer are smaller than that of seeds, and the change of monodispersity among them is not obvious and the monodispersity of particles prepared under higher reaction temperature is higher than that of seeds and those particles prepared under lower reaction temperature. With increasing reaction time, thermoresponsive characteristics of microspheres increases. While thermoresponsive characteristics of microspheres decreases sharply with increasing reaction temperature. The results display preparation of IPN-structured microspheres is so careful to need longer reaction time and lower reaction temperature.