Microparticles injectable

Nakatani, K. and Sekine, T, Single-microparticle injection and microabsorptiometry Direct analysis of sorption processes, J. Colloid Interf. Sci., 225, 251, 2000. 

The next paper we will comment on in this section is a letter by Nakatami et al. [147] in which they describe a microscale technique to study the dynamics of adsorption. This technique, the single-microparticle injection, is basically an optical method that uses Lambert-Beer law to follow the concentration of methylene blue on the surface of a silica gel microparticle. Their main conclusions are that equilibrium is attained within 20 min, Langmuir equation describes the experimental adsorption isotherm, methylene blue molecules penetrate into the pores and the whole process is controlled by adsorbate diffusion in water. 

Preliminary biological tests showed the compatibility of Im Hb with blood and the theoretical possibility of intravenous injection and functioning in the organism. The use of microparticles of Im Hb with a covalently bonded marker permitted the determination of the time of microparticle circulation in the blood channel of rats. After 7 h. of observation, up to 30% of the introduced amount of Im Hb was retained in the blood of the animals. 

Tice, T. R., Lewis, D. H., Cowsar, D. R., and Beck, L. R., Stolle Research and Development Co., Injectable, long-acting microparticle formulation for the delivery of antiinflammatory agents, Eur. Patent Appl. 102265 A2, March 7, 1984. 

W Im-Emsap, GA Brazeau, JW Simpkins, R Bodmeier. Sustained drug delivery of 17-/1 estradiol from injectable biodegradble in situ forming microparticles (ISM) system. AAPS PharmSci Supplement 2(4), AAPS Annual Meeting Abstracts, 2000. 

Jiang W, Gupta RK, Deshpande MC et al (2005) Biodegradable poly(lactic-co-glycolic acid) microparticles for injectable delivery of vaccine antigens. Adv Drug Deliv Rev 57 391 —410... 

Lipid microparticles and nanopellets for oral use were first described by Speiser [11]. Nanopellets are prepared by dispersing melted lipids with high-speed mixers or via ultrasound techniques. Lipospheres developed by Domb are also prepared from dispersed lipids by stirring and sonication [12]. These preparations may contain a high degree of microparticles, which thus excludes an intravenous injection. For other routes of application (e.g., peroral administration), these microparticles might not be a serious problem. Furthermore, the dispersions may be contaminated by metal shed. With optimized conditions, however, mean particles sizes of 1(X) to 200 nm are possible [13]. 

Another example of a delivery system based on microbubbles and ultrasound is the delivery of circulating microparticles (polymer latex beads) or fluorescent red blood cells outside of the capillaries into the surrounding tissues by the action of ultrasound on the co-injected Optison microbubbles [79]. Interestingly, polymer beads and red blood cells could be detected tens of micrometers away from the capillaries where the bubble destruction took place. This may imply that during rapid destruction of a microbubble in a very strong ultrasound field, adjacent microsphere beads in the bloodstream can be propelled deep into the surrounding tissues. 

The biodistribution of particles with different sizes of 290 nm ( nanoparticles ) and 1.7 pm ( microparticles ) was investigated in rats by Li et al. [36] following i.v. injection at doses of 50 mgl kg Both types of particles were taken... 

Although widely perceived as being innocuous, studies on the intravenous use of gelatin as a blood expander showed a number of unexpected toxicides in clinical practice. For this reason, injected gelatin microparticles might be anticipated to suffer from the same effects and should not be regarded as being completely innocuous. 

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. 

As reported later in Chapter 9.9 of this book, active-ingredient-containing polymeric micro-particles are widely used in technological and medical applications. For example, these particles are suitable as drug-delivery devices and can control the pharmaceutical release-rate over time. The particle size is absolutely important when dealing with drug-delivery devices. Very small particles can be inhaled, while larger ones can be injected into the blood stream. Therefore, it is important to control the microparticle size in the production. 

From Table 8.3-3 it is evident that the recycled CO2 (stream C02IN1) is not pure. To assure a THF flow rate of 5.76 kg/h in the precipitator, the THF make-up has to be less than this amount. As a consequence, the polymer solution injected in the precipitator is more concentrated than was tested in the pilot plant [4], In this particular case, the different inlet concentration should not make any difference in the precipitate morphology. However, in general, changing the polymer concentration can lead to the formation of either microparticles of small size or to polymer fibres [5]. 

Chromatographic System (See Chromatography, Appendix IIIA.) Set up the system with reference to High-Performance Liquid Chromatography. The chromatograph has a 254-nm detector and a 15-cm x 4.6-mm column that contains 5-to 10-mm porous microparticles of silica bonded to octylsilane (Zorbax 8, or equivalent). Set the flow rate to about 2 mL/ min. Chromatograph three replicate injections of the Standard Preparation, and record the peak responses as directed under Procedure. The relative standard deviation is not more than 2.0%, and the resolution factor between nitrilotriacetic acid and Calcium Disodium EDTA is not less than 4.0. 

Procedure (See Chromatography, Appendix IIA.) Use a high-performance liquid chromatograph equipped with an ultraviolet detector that measures absorption at 254 nm and a 25- to 30-cm x 4-mm (id) stainless-steel column, or equivalent, packed with octadecyl silane chemically bonded to porous silica or ceramic microparticles 5 to 10 pun in diameter, or equivalent. Maintain the mobile phase at a pressure and flow rate capable of giving the required resolution (see below). Inject a volume, up to 25 pL, of the System Suitability Solution in a similar manner. Calculate the resolution, R (>3.6), between calcium formyltetrahydrofolate and Folic Acid by the equation... 

IdUrd loaded microparticles within the tumor might increase the lethal effects of y-radiation of malignant cells having incorporated IdUrd. The particles can be administered by stereotactic injection, a precise surgical injection technique [207]. This approach requires microparticles of 40-50 pm in size releasing in vivo their content over 6 weeks, the standard period during which a radiotherapy course must be applied. 

Masters and Domb [250] reported on an injectable drug delivery system that uses liposomes [251] to release the local anesthetic, bupivacaine, from a liposomal matrix that is both biodegradable and biocompatible to produce SLAB. Bupivacaine due to its minimum vasodilating properties was preferred to other local anesthetics (e.g., lidocaine) allowing the released drug to remain at the site of injection longer [252]. Lipospheres are an aqueous microdispersion of water insoluble, spherical microparticles (0.2 to 100 pm in diameter), each consisting... 

---