Microencapsulation by solvent evaporation: state of the art for process engineering approaches (original) (raw)
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Microencapsulation technique by solvent evaporation method (Study of effect of process variables
INTERNATIONAL JOURNAL OF PHARMACY & LIFE SCIENCES , 2011
The preparation of microsphere by solvent evaporation method has been studied extensively to prepare a microsphere using biodegradable polymer. The properties of biodegradable microsphere of poly (lactic acid) (PLA) and (acid lactic-co-glycolic) (PLGA) have been extensively investigated. The encapsulation of highly water soluble compounds including proteins and peptides is providing challenges to the pharmaceutics person. The successful encapsulation of such entities requires high drug loading in the microsphere, prevention of protein degradation by the encapsulation method, and predictable release of the drug compound from the microsphere. Multiple emulsion techniques and some other innovative modifications have been made to the conventional solvent evaporation process. A several process variable affecting the quality of product has been studies in this review.
Solvent Evaporation Techniques as Promising Advancement in Microencapsulation
2013
In recent times solvent evaporation techniques have gained prominence in microencapsulation process. Solvent evaporation techniques are broadly classified into emulsification solventevaporation and extraction methods. Several variations have been developed recently based on this technology. Using solvent evaporation methods we can regulate microsphere morphology and other characteristics to the desired level for the targeted delivery of bioactives like peptides and vaccines using various biomaterials as carriers. Several methods of solvent evaporation, core and coat materials used, emulsion stabilizers, and process variables were discussed in detail with due interest of recent advancements in this area of research. This technology is showing a promising future for drug targeting and throwing challenges to pharmaceutical scientist such as: scale-up problems, use of non-organic solvents, use of alternative biodegradable polymers, and the application of a viable hybrid technology by amalgamating various techniques of microencapsulation to overcome the problems of peptide degradation during the process and stability of microspheres after the process.
Discussion and outlook 145 Curriculum Vitae 149 Publications 149 [2] A. Smith, I.M. Hunneyball, Evaluation of poly(lactic acid) as a biodegrad¬ able drug delivery system for parenteral administration, Int. J. Pharm. 30 (1986)215-220. Background and purpose 3 [3] J.M. Anderson, M.S. Shive, Biodegradation and biocompatibility of PLA and PLGA microspheres, Adv. Drug. contribution to over¬ coming the problem of residual solvents in biodegradable microspheres prepared by coacervation, Eur. irradiation for terminal sterilization of 17ß-estradiol loaded poly-(D.L-lactide-co-glycolide) microspheres, J. Control. Release 61 (1999) 203-217. [7] A. Hausberger, R. Kenley, P.P. De Luca, Gamma irradiation effects on molecular weight and in vitro degradation of poly(D,L-lactide-coglycolide) microparticles, Pharm. Res. 12 (1995) 851-856. 4 Background and purpose Abstract 5 Abstract
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.
Journal of Controlled Release, 2005
The therapeutic benefit of microencapsulated drugs and vaccines brought forth the need to prepare such particles in larger quantities and in sufficient quality suitable for clinical trials and commercialisation. Very commonly, microencapsulation processes are based on the principle of so-called bsolvent extraction/evaporationQ. While initial labscale experiments are frequently performed in simple beaker/stirrer setups, clinical trials and market introduction require more sophisticated technologies, allowing for economic, robust, well-controllable and aseptic production of microspheres. To this aim, various technologies have been examined for microsphere preparation, among them are static mixing, extrusion through needles, membranes and microfabricated microchannel devices, dripping using electrostatic forces and ultrasonic jet excitation. This article reviews the current state of the art in solvent extraction/evaporation-based microencapsulation technologies. Its focus is on process-related aspects, as described in the scientific and patent literature. Our findings will be outlined according to the four major substeps of microsphere preparation by solvent extraction/evaporation, namely, (i) incorporation of the bioactive compound, (ii) formation of the microdroplets, (iii) solvent removal and (iv) harvesting and drying the particles. Both, well-established and more advanced technologies will be reviewed.
Microencapsulation techniques, factors influencing encapsulation efficiency: a review
The Internet Journal of …, 2009
Microencapsulation is one of the quality preservation techniques of sensitive substances and a method for production of materials with new valuable properties. Microencapsulation is a process of enclosing micron-sized particles in a polymeric shell. There are different techniques available for the encapsulation of drug entities. The encapsulation efficiency of the microparticle or microsphere or microcapsule depends upon different factors like concentration of the polymer, solubility of polymer in solvent, rate of solvent removal, solubility of organic solvent in water, etc. The present article provides a literature review of different microencapsulation techniques and different factors influencing the encapsulation efficiency of the microencapsulation technique.
Molecular Pharmaceutics, 2006
A new microencapsulation technique based on the solvent exchange method was implemented using an ultrasonic atomizer system to encapsulate a protein drug in mild conditions. The reservoir-type microcapsules encapsulating lysozyme as a model protein were prepared by inducing collisions between the aqueous droplets containing lysozyme and the droplets of organic solvent with dissolved poly(lactic acid-co-glycolic acid) (PLGA).The main focus of the study was to examine formulation variables on the size and the encapsulation efficiency of the formed microcapsules. The formulation variables examined were concentrations of mannose in the aqueous cores, NaCl in the aqueous collection medium, and PLGA in organic solvent. The mean diameter of the microcapsules ranged from 40 µm to 100 µm. Smaller microcapsules showed lower encapsulation efficiencies. The resulting microcapsules released native lysozyme in a sustained manner, and the release rate was dependent on the formulation conditions, such as the concentration and molecular weight of the polymer used. The solvent exchange method does not induce lysozyme aggregation and loss of its biological activity. The solvent exchange method, implemented by the ultrasonic atomizer system, provides an effective tool to prepare reservoir-type microcapsules for delivering proteins. . † Present address: Department of Advanced Polymer and Fiber Materials, Kyung Hee University, Gyeonggi-do 449-701, South Korea. (1) Bartus, R. T.; Tracy, M. A.; Emerich, D. F.; Zale, S. E. Sustained delivery of proteins for novel therapeutic agents. Science 1998, 281, 1161-1162. (2) Sinha, V. R.; Trehan, A. Biodegradable microspheres for protein delivery. J. Controlled Release 2003, 90, 261-280. (3) Tamber, H.; Johansen, P.; Merkle, H. P.; Gander, B. Formulation aspects of biodegradable polymeric microspheres for antigen delivery.
Biological & Pharmaceutical Bulletin, 2007
The microencapsulation techniques are widely used in the pharmaceutical field. 1) Among them, emulsion solvent evaporation method has taken considerable attention in recent years, and numerous methods to manipulate a drug release behavior have been reported. 2) Several preparation variables influencing on the properties of microspheres have been identified, including solvent type, solvent removal rate, preparation temperature, composition and viscosity of polymer, and drug loading amount. In a previous study, we illustrated the effect of temperature-increase rate in the solvent evaporation process (referred to as the temperature-increase method hereafter) on the drug release property of the microspheres. 3) In this method, the preparative vessel was heated up at the constant rate in order to evaporate the dispersed solvent. By means of the temperature-increase method, microspheres showing constant drug release were prepared over a short period of time. Although a variety of studies has been conducted, the effects of poor solvent in the dispersed phase on the physical properties and drug release characteristics are not well-documented. The aim of the current work was to evaluate the effects of poor solvent in the dispersed phase on drug release from the microspheres when the temperature-increase method was employed for the emulsion solvent evaporation process. In this study, model microspheres were prepared from theophylline (TH) and hydrophobic dextran derivative (PDME). TH was used as a representative drug since sustained-release formulations are desirable because of the short elimination half-life in humans. PDME was selected as a water-insoluble polymer; it is used for contact lenses in the industrial field. Mixtures of acetone and water were used as the dispersed phase and liquid paraffin as the continuous phase. The microspheres were characterized by their size and drug loading efficiency. The morphology of the microspheres was then observed by scanning electron microscopy. In addition, drug release was examined and its kinetics were analyzed. MATERIALS AND METHODS Materials TH as an anhydrous form was purchased from Sigma Chemical Co. (St. Luis, MO, U.S.A.) and was used after sieving through a 200-mesh sieve (less than 75 mm). PDME was kindly donated by Meito Sangyo Co., Ltd. (Nagoya, Japan) and was used without further purification. PDME is prepared from dextran (Mw 40000) by substitution of 0.58 mol acetyl, 0.81 mol propionyl, 1.42 mol butyryl and 0.16 mol methacryloyl per anhydroglucose unit of dextran. Acetone was purchased from Wako Pure Chemical Industry, Ltd. (Osaka, Japan). Liquid paraffin conforming to JP standard was obtained from Iwaki Seiyaku Co., Ltd. (Tokyo, Japan). Sucrose-ester (DKF-10) was generously supplied by Dai-ichi Kogyo Seiyaku Co., Ltd. (Kyoto, Japan) and was used as an emulsifier. Polyoxyethylene (20) sorbitan monolaurate (Tween 20) was purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). Ultra purified water generated by Direct-Q (Nihon Millipore Ltd., Tokyo, Japan) was used for preparation of the dispersed phase. All other chemicals were of special reagent grade and were used as received. Preparation of Microspheres PDME (6.75 g) was dissolved into 15 ml of a mixture of acetone and water. TH (2.25 g) was then suspended in the PDME solution by stirring with a magnetic stirrer. The resultant suspension was poured into 150 ml of liquid paraffin containing 0.75 g of DKF-10 in a vessel settled into a water bath under agitation (400 rpm, 1 propeller) at 20°C. Following emulsification for 30 min at this temperature in the water bath, the system was heated up to 60°C at the temperature-increase rate of 30°C/h. In order to remove the organic solution completely,
Aspirin dissolution profiles from different particle size ranges of Eudragit RS100 microcapsules were studied in relation to the studied microcapsule structures. The results showed that there is no burst effect and the total amount of drug released from different particle size ranges prepared with the same or different TDC are more than 80% during 12 hr. The release data indicated the closest of the dissolution profile in every case. The values of standard deviation at every time unit were also used as an indication for the release data distribution around the mean of drug release. The model independent methods were used to prove the dissolution profile similarity of Aspirin from different particle size ranges microcapsules prepared by using the same theoretical drug content. Accordingly the mean dissolution profile of Aspirin from different particle size ranges of Eudragit RS100 prepared by using the same TDC was used to represent the drug release profile and also to study the effect of increasing TDC. The mean release data showed the closest of the dissolution profiles from different products prepared by using different TDC. Again the independent models were used to prove the similarity of the dissolution profile of Aspirin from different Eudragit RS100 microcapsules prepared on using different TDC. Accordingly it was concluded that the overall Aspirin dissolution profile can be used to represent the drug release profile from different particle size ranges of Eudragit RS100 microcapsules prepared by using the same or different TDC.
2015
Irin Dewan *1, , Swarnali Islam Khandaker 2 and Md. Sohel Rana 1 Department of Pharmacy , Jahangirnagar University, Savar, Dhaka, Bangladesh Pharmaceutical Technology Research Laboratory , Department of Pharmacy, University of Asia Pacific, Dhanmondi, Dhaka-1209, Bangladesh ABSTRACT: Glibenclamide is an oral anti-hyperglycemic agent designed intended for the management of non-insulin-dependent diabetes mellitus (NIDDM). In certain conditions conventional drug release pattern is not suitable similar to Diabetes mellitus, cardiovascular diseases and many more diseases, this present study has taken a challenge to formulate controlled release microspheres by using different polymers. An effort has been given to prepare controlled release microspheres along with Ethyl cellulose, Eudragit RS/RL100 and Methocel K15, 100M by using non-aqueous emulsion solvent evaporation method. UV-Spectrophotometric was applied to assay the drug content and in vitro dissolution studies according to USP pad...