Preparation and evaluation of novel blend microspheres of poly(lactic‐co‐glycolic)acid and pluronic F68/127 for controlled release of repaglinide (original) (raw)
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European Journal of Pharmaceutics and Biopharmaceutics, 2008
Taking ABT627 as a hydrophobic model drug, poly-(lactic-co-glycolic acid) (PLGA) microspheres were prepared by an emulsion solvent evaporation method. Various process parameters, such as continuous phase/dispersed phase (CP/DP) ratio, polymer concentration, initial drug loading, polyvinyl alcohol concentration and pH, on the characteristics of microspheres and in vitro drug release pattern of ABT627 were investigated. Internal morphology of the microspheres was observed with scanning electron microscopy by stereological method. CP/DP is a critical factor in preparing microspheres and drug loading increased significantly with increasing CP/DP ratios accompanied by a remarkably decreased burst release. At CP/DP ratio 20, microspheres with a core-shell structure were formed and the internal porosity of the microspheres decreased with increasing CP/DP ratio. Increase in PLGA concentration led to increased particle sizes and decreased drug release rates. ABT627 release rate increased considerably with increasing PVA concentrations in the continuous phase from 0.1% to 0.5%. The maximum solubility of ABT627 in PLGA was approximately 30%, under which ABT627 was dispersed in PLGA matrix in a molecular state. Increase in initial drug loading had no significant influence on particle size, drug encapsulation efficiency, burst release and internal morphology. However, drug release rate decreased at higher drug loading. Independent of process parameters, ABT627 was slowly released from the PLGA microspheres over 30 days, by a combination of diffusion and polymer degradation. During the first 13 days, ABT627 was mainly released by the mechanism of diffusion demonstrated by the unchanged internal morphology. In contrast, a core-shell structure of the microspheres was observed after being incubated in the release medium for 17 days, independent of drug loading, implying that the ABT627/PLGA microspheres degraded by autocatalytic effect, starting from inside of the matrix. In conclusion, hydrophobic drug release from the PLGA microspheres is mainly dependent on the internal morphology and drug distribution state in the microspheres.
Sustained Release Delivery of Repaglinide by Biodegradable Microspheres
Journal of Drug Delivery and Therapeutics, 2017
The primary objective of the present study was to prepare repaglinide microspheres for the sustained delivery of the drug for better patient care in the management of diabetics. The biodegradable microspheres of repaglinide is prepare using poly (lactic-co-glycolic acid) (PLGA) by emulsion solvent evaporation technique. The microspheres are prepared with different drug-to-carrier ratios and considering other variables (i.e. solvent, surfactant and stirrer speed) as well. The evaluation of microspheres prepared are perform on the basis of various parameters like particle size, percentage yield, drug entrapment efficiency, surface morphology, drug-polymer interaction (FT-IR study), in vitro drug release kinetics and stability studies. SEM reveals that microspheres are spherical and has nearly smooth surface morphology. The percentage yield and drug entrapment efficiency is quite well for all the formulations. FT-IR spectra show that there is no chemical interaction between the drug a...
Journal of Biomedical Materials Research, 2004
This article describes the effects of six processing parameters on the release kinetics of a model drug Texas red dextran (TRD) from poly(propylene fumarate)/poly(lacticco-glycolic acid) (PPF/PLGA) blend microspheres as well as the degradation of these microspheres. The microspheres were fabricated using a double emulsion-solvent extraction technique in which the following six parameters were varied: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) in the internal aqueous phase, and poly-(vinyl alcohol) concentration in the external aqueous phase. We have previously characterized these microspheres in terms of microsphere morphology, size distribution, and TRD entrapment efficiency. In this work, the TRD release profiles in phosphate-buffered saline were determined and all formulations showed an initial burst release in the first 2 days followed by a decreased sustained release over a 38day period. The initial burst release varied from 5.1 (Ϯ1.1) to 67.7 (Ϯ3.4)% of the entrapped TRD, and was affected most by the viscosity of the polymer solution used for micro-sphere fabrication. The sustained release between day 2 and day 38 ranged from 7.9 (Ϯ0.8) to 27.2 (Ϯ3.1)% of the entrapped TRD. During 11 weeks of in vitro degradation, the mass of the microspheres remained relatively constant for the first 3 weeks after which it decreased dramatically, whereas the molecular weight of the polymers decreased immediately upon placement in phosphate-buffered saline. Increasing the PPF content in the PPF/PLGA blend resulted in slower microsphere degradation. Overall, this study provides further understanding of the effects of various processing parameters on the release kinetics from PPF/PLGA blend microspheres thus allowing modulation of drug release to achieve a wide spectrum of release profiles.
J. Braz. Chem. Soc, 2010
Foi desenvolvida uma nova técnica que possibilita o monitoramento da liberação de fármacos encapsulados, sem a separação das partículas do meio de liberação, usando espectroscopia de refletância difusa. Foram realizados estudos de liberação do cloro(5,10,15,20-tetrafenilporfirinato) de índio(III) (InTPP) a partir de micro e nanoesferas do copolímero do ácido lático-co-glicólico (PLGA). A liberação do InTPP foi bifásica, com uma liberação rápida inicial seguida por uma segunda fase mais lenta de liberação. Modelos matemáticos aplicados aos perfis de liberação mostraram que a liberação do InTPP a partir das nanoesferas foi controlada por difusão, o que é esperado para uma substância homogeneamente dispersa dentro da esfera. Contudo, devido a larga distribuição de tamanho das microesferas carregadas com InTPP, os perfis de liberação foram irregulares, dificultando o adequado ajuste dos nossos modelos matemáticos. Análise confocal das micropartículas mostrou que o InTPP aparenta ser homogeneamente distribuído dentro das microesferas e nenhuma distribuição preferencial do InTPP foi observada em direção ao interior ou a zona superficial da esfera.
International Journal of Pharmacy and Pharmaceutical Sciences, 2017
Objective: The purpose of this research work was to develop and evaluate microspheres appropriate for controlled release of zidovudine (AZT). Methods: The AZT loaded polylactide-co-glycolide (PLGA) microspheres were prepared by W/O/O double emulsion solvent diffusion method. Compatibility of drug and polymer was studied by Fourier-transform infrared spectroscopy (FTIR). The influence of formulation factors (drug: polymer ratio, stirring speed, the concentration of surfactant) on particle size encapsulation efficiency and in vitro release characteristics of the microspheres was investigated. Release kinetics was studied and stability study was performed as per ICH guidelines. Results: Scanning electron microscopy (SEM) images show good reproducibility of microspheres from different batches. The average particle size was in the range of 216-306 μm. The drug-loaded microspheres showed 74.42±5.08% entrapment efficiency. The cumulative percentage released in phosphate Buffer solution (PBS) buffer was found to be 55.32±5.89 to 74.42±5.08 %. The highest regressions (0.981) were obtained for zero order kinetics followed by Higuchi (0.968) and first order (0.803). Conclusion: Microsphere prepared by double emulsion solvent diffusion method was investigated and the results revealed that 216-306 μm microsphere was successfully encapsulated in a polymer. FT-IR analysis, entrapment efficiency and SEM Studies revealed the good reproducibility from batch to batch. The microspheres were of an appropriate size and suitable for oral administration. Thus the current investigation show promising results of PLGA microspheres as a matrix for drug delivery and merit for In vivo studies for scale up the technology.
Colloids and Surfaces B-biointerfaces, 2009
Biodegradable polymeric microspheres are ideal vehicles for controlled delivery applications of drugs, peptides and proteins. Amongst them, poly(lactic-co-glycolic acid) (PLGA) has generated enormous interest due to their favorable properties and also has been approved by FDA for drug delivery. Insulin-loaded PLGA microparticles were prepared by our developed single phase oil in oil (o/o) emulsion solvent evaporation technique. Insulin, a model protein, was successfully loaded into microparticles by changing experimental variables such as polymer molecular weight, polymer concentration, surfactant concentration and stirring speed in order to optimize process variables on drug encapsulation efficiency, release rates, size and size distribution. A 2 4 full factorial design was employed to evaluate systematically the combined effect of variables on responses. Scanning electron microscope (SEM) confirmed spherical shapes, smooth surface morphology and microsphere structure without aggregation. FTIR and DSC results showed drug-polymer interaction. The encapsulation efficiency of insulin was mainly influenced by surfactant concentration. Moreover, polymer concentration and polymer molecular weight affected burst release of drug and size characteristics of microspheres, respectively. It was concluded that using PLGA with higher molecular weight, high surfactant and polymer concentrations led to a more appropriate encapsulation efficiency of insulin with low burst effect and desirable release pattern.
DESIGN AND CHARACTERIZATION OF POLYMERIC MICROSPHERES FOR ORAL ADMINISTRATION
An appropriately designed sustained or controlled release drug delivery system can be a major advance towards solving the problem associated with the existing drug delivery system. Microspheres as a novel drug delivery system for oral administration are having the feasibility of carrying the drug. These are the monolithic spheres or therapeutic agent distributed throughout the matrix as a molecular dispersion of particles. Rational behind the drug encapsulation into microspheres is preparation of suitable formulation with longer duration of action for control release thereby sustaining the role of release of core material by rupture of polymeric wall. This will also reduce the dosing frequency and helps to improve the patient compliance. The aim of present work was to produce and characterize Repaglinide (Rg) polymeric microspheres by solvent evaporation method, in an attempt to obtain a delivery system adequate for the treatment of diabetes. Batches were prepared with different ratios of drug and polymer. Polymeric microspheres of Repaglinide were successfully prepared using Eudragit RSPO as polymer by emulsion solvent evaporation method. The prepared microspheres were evaluated for percentage yield, particle size, and drug entrapment efficiency, scanning electron microscopy, micromeritic studies and in vitro drug release study. From all the evaluation parameters the batch which is considered to be optimized batch, the final formulation i.e. tablet were prepared from the microspheres prepared in that optimized batch.
AAPS PharmSciTech, 2003
The objective of this research was to optimize the processing parameters for poly(D,L-lactide-coglycolide) (PLGA) microspheres of 5-fluorouracil (5-FU) and to mathematically relate the process parameters and properties of microspheres. Microspheres were prepared by a water-in-oil-in-water emulsion solvent evaporation technique. A 3 2 factorial design was employed to study the effect of the volume of the internal phase of the primary emulsion and the volume of the external phase of the secondary emulsion on yield, particle size, and encapsulation efficiency of microspheres. An increase in the volume of the internal phase of the primary emulsion resulted in a decrease in yield and encapsulation efficiency and an increase in particle size of microspheres. When the volume of the external phase of the secondary emulsion was increased, a decrease in yield, particle size, and encapsulation efficiency was observed. Microspheres with good batch-to-batch reproducibility could be produced. Scanning electron microscopic study indicated that microspheres existed as aggregates.
The Open Conference Proceedings Journal, 2012
Many existing pharmaceuticals are rendered ineffective in the treatment of central nervous system (CNS) diseases due to the highly challenging aspects of drug delivery to the most delicate organ namely brain. In order to overcome the problems of delivering neuroprotective agents to the CNS, numerous strategies have been proposed. Among the developed drug carrier to the CNS, poly lactic-co-glycolic acid (PLGA) microspheres have shown desirable outcomes because of their biocompatibility, biodegradability, convenient processability and resorbability through natural pathways. Meanwhile, a comprehensive understanding of the factors affecting drug release mechanisms from microspheres is critical to the design of optimal drug-loaded microparticles. In the present study, we investigated the physicochemical and emulsifying properties of synthesized L-dopa-loaded microsphere. A series of microspheres of different compositions were prepared by varying the salt (NaCl) content, stabilizer content and homogenizer speed. The prepared microspheres were loaded with L-dopa and characterized by SEM techniques to gain insights into the structural and morphological features. The microspheres size was also determined to elucidate the influence of varying formulation and dynamic properties on the drug release pattern. After evaluating morphology and size of the microspheres, the optimum formulation and process parameters including speed of stirring applied for emulsification, drug concentration, amounts of surfactant and NaCl content in the solvent, were revealed using taguchi software according to the prolonged drug release pattern of microspheres.