Microencapsulation microparticle

The steroid-loaded formulations are prepared by a patented solvent evaporation process (45,46). Basically, the wall-forming polymer and the steix>id are added to a volatile, water-immiscible solvent. The dispersion or solution is added to an aqueous solution to form an oil-in-water emulsion. The volatile solvent is then removed to afford solid microparticles. The microparticles are usually subd vided with sieves to isolate fractions of the desired diameters. It is i nper-ative that a reliable and reproducible microencapsulation procedure be used to fabricate long-acting formulations. 

A composition based on diketopiperazine derivatives (3,6-bis (N-fumaryl-N-(n-butyl) amino-2, 5-diketopiperazine) has been investigated as a pulmonary drug delivery system, termed Technospheres (Pharmaceutical Discovery Corp., Elmsford, NY) (Pohl et al. 2000 Steiner et al. 2002). The diketopiperazine derivatives self-assemble into microparticles at low pH with a mean diameter of approximately 2 pm. During self-assembly, diketopiperazine derivatives microencapsulate peptides present in the solution. Insulin incorporated in diketopiperazine derivatives (TI) was administered to five healthy humans by the use of a capsule-based inhaler with a passive powder deagglomeration mechanism. Relative and absolute bioavailability of TI in the first 3 hours (0-180 min) were 26 12% and 15 5%, and for 6 hours (0-360 min) 16 8% and 16 6%, respectively (Steiner et al. 2002). The time to peak action for glucose infusion rates was shorter with both IV (14 6 min) injection and inhalation (39 36 min), as compared to SC administration (163 25 min). This rapid absorption of insulin would be beneficial for diabetic patients who need to rapidly affect their glucose levels. 

Yeh, M. K. (2000), The stability of insulin in biodegradable microparticles based on blends of lactide polymers and polyethylene glycol,/. Microencapsul., 17, 743-756. 

Kim, H. K., and Park, T. G. (2001), Microencapsulation of dissociable human growth hormone aggregates within poly(o,i.-lactic-co-glycolic acid) microparticles for sustained release, Int. J. Pharm., 229,107-116. 

Yeh, M. K., and Chiang, C. H. (2004), Inactive Vibrio cholerae whole-cell vaccine-loaded biodegradable microparticles In vitro release and oral vaccination, J. Microencapsul.,... 

Ezpeleta, I. Irache, J.M. Gueguen, J. Orecchioni, A.M. Properties of glutaraldehyde cross-linked vicilin nano- and microparticles. J. Microencapsulation 1997,14 (5), 557-565. 

Microencapsulation technology has been used from 1930s in packaging flavors and vitamins. Since the first commercial product was introduced for the carbonless copying paper, the technology has advanced to a new level. Various microencapsulation techniques are available nowadays, and the microencapsulated products are widely used in pharmaceutical, biomedical, agricultural, food, consumer products, and cosmetic industries. Representative applications of microparticles in the pharmaceutical and biomedical industries include ... 

With the recent advance of biotechnology and polymer chemistry, the use of microparticle systems will continue to grow for a variety of applications. The objective of this article is to provide a review of the technical aspects of the microencapsulation techniques that have been widely used in the pharmaceutical industry and recent advances of the technology so that the pharmaceutical scientists can take full advantage of the existing assets of this area in developing new microparticle systems. 

The coacervation method is one of the earliest microencapsulation techniques, which has been used for various consumer products. This method is based on separation of a solution of hydrophilic polymer(s) into two phases, which are small droplets of a dense polymer-rich phase and a dilute liquid phase. Coacervation can be divided into simple and complex coacervation depending on the number of polymers that are involved in the formation of microparticles. 

Despite the extensive use of PLGA polymers in the microencapsulation arena, it has been found through decades of research that the PLGA microparticle systems are not universally suited for different applications. One of the limitations in the prevalent PLGA systems is that bulk hydrolysis of the polymer induces acidification of microenvironment of the microparticles, which can be detrimental to various payloads such as proteins and nucleic acids. In addition, their drug release kinetics are not readily tunable and, thus, are inappropriate for specific applications.f ... 

Debenedetti and coworkers (88,89) provided one of the first examples of microencapsulation of a drug in the polymeric matrix. Richard and coworkers (90) provided a recent example of the microencapsulation process when they produced microparticles with the encapsulated model protein that showed sustained release. Foster and coworkers (87) also reported precipitation of copper-indomethacin by PVP with a 96-fold enhancement in the dissolution rate of indomethacin. These examples clearly demonstrated the advantages of using supercritical fluid processing for the preparation of polymer-drug formulations with potentially improved therapeutic properties. 

Bleich J, Mueller BW. Production of drug loaded microparticles by the use of supercritical gases with the aerosol solvent extraction system (ASES) process. J Microencapsul 1996 13 131-139. 

Esposito, E. et al., Biodegradable microparticles for sustained delivery of tetracycline to the periodontal pocket formulatory and drug release studies, J. Microencapsul., 14, 175, 1997. 

The simplest procedure of microencapsulating Cl by polycondensation consists of the following operations. One of the monomers is dissolved in an organic solvent and the other in water. A Cl dispersion is introduced into one of the phases. The organic and water phases should not mix and the solvent should be compatible with the polymer formed at polycondensation. Polycondensation is initiated slowly (accelerated by dissolved catalysts) on the surface of Cl microparticles by joining the phases in the dispersion nozzle. The microcapsules are separated from the reaction blend by either floating or dipping. 

In the microencapsulation of probiotics, matrices used in the formula cannot be cytotoxic or antimicrobial. When microparticles go through the stomach, bacteria have to continue retained and protected from the external acid environment, and they should be released only in the intestines, where immunological signaling will occur (Cook et al., 2012). Little is known about the effect of microencapsulation with lipid matrices on probiotic survival. However, it is known than fat/oils are barriers against oxygen and moisture. 

Gamboa et al. (2011) also microencapsulated vitamin E using spray chilling. However, their aim was to microencapsulate tocopherol using chemically interesterified low trans fat. Besides characterizing the microparticles, the authors used the tocopherol-loaded microparticles in a food matrix and analyzed the sensory acceptance of the product. It was observed that microparticles obtained by spray chilling presented satisfactory release profile. The use of microparticles loaded with tocopherol did not compromise the sensory characteristics of the product. In both studies (Albertini et al., 2008 Gamboa et al., 2011), there was no description of the oxidative stability of vitamin E after the encapsulation. 

In terms of drug microencapsulation, DSC results alone are not enough to determine the physical state of the bioactive compound in the microparticles. Although the analysis may identify and quantify thermal events, it does not show the cause of the event. Then, in order to investigate these aspects in greater detail, HTM, and XRD are recommended (Passerini et al 2003). 

Ilic et al. (2009) used a mixture of acetonitrile and water (80 20, v/v) as the solvent for the extraction of the drug from the microparticles. Then, the drug was quantified by high efficiency liquid chromatography—HPLC. In a study of insulin microencapsulation, the authors proposed that microparticles were initially stirred in a vortex with chloroform, and then insulin was extracted with HCl 0.01 M. After that, the solution was centrifuged and, in the end, insulin was quantified by HPLC (Maschke et al., 2007). 

Takka, S. and Acarturk, E. Calcium alginate microparticles for oral administration I Effect of sodium alginate type on drug release and drug entrapment efficiency. J. Microencapsul. 16 (1999) 275-290. 

Salauen, F. Bedek, G. Devaux, E. Dupont, D. Gengembre, L. Microencapsulation of a cooling agent by interfacial polymerization Influence of the parameters of encapsulation on poly(urethane-urea) microparticles characteristics. Journal of Membrane Science (2011), 370(1-2), 23-33. 

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