Parenteral application

Unfortunately, the relatively low solubility of /8-cyclodextrin has precluded its widespread use as a solubilizing agent. To enhance the solubility of /8-cyclodextrin, much work has been carried out on possible derivatizations of the /8-cyclodextrin skeleton. 2-Hydroxypropyl-/3-cyclodextrin has been found to exhibit the desired enhanced solubility, while still retaining the optimal binding characteristics of underivatized /8-cyclodextrin. In addition, this derivative is relatively nontoxic and may even be used in parenteral applications [63],... 

Biological considerations No limitations. Preferable to water in parenteral applications... 

Besides parenteral application of microspheres and nanoparticles for cell selective delivery of drugs, they have more recently been studied for their application in oral delivery of peptides and peptidomimetics [30]. Immunological tolerance induction against beta-lac-toglobulin could be achieved by application of this protein in a poly-lactic-glycolide microsphere formulation [31]. 

Engelhart, K., Jentzsch, A. M., Eiirst, P., and Biesalski, H. K. (1998). Short-term parenteral application of a-tocopherol leads to increased concentration in plasma and tissues of the rat. Free Rad. Res. 29, 421 26. 

Prodrug, fosphenytoin rapidly converted to phenytoin in vivo minimal activity before conversion water soluble, thus more suitable for parenteral applications does not require cardiac monitoring can be administered at faster rate no IV filter required compatible with both saline and dextrose mixtures requires refrigeration... 

Clinical use Diflunisal (Brogden et al., 1980) is a nonsteroidal anti-inflammatory drug used in the treatment of mild to moderate pain including osteoarthritis, rheumatoid arthritis and primary dysmenorrhoea. It is used as base or lysine- or arginine-salt for oral or parenteral application. 

There are certain limitations with cosolvent approach, as with any other approaches, as poor tasting cosolvent (PG), adverse physiological effects (e.g., alcohol) and potential of cosolvent on metabolic enzymes, transporters, and distribution and hence unintentionally altering drug pharmacokinetic properties. For solubilized parenteral application, choice of cosolvents is further limited by physiological acceptance, as well as precipitation on injection and pain on administration. However, the approach remains popular both for oral as well as parenteral application as demonstrated by numerous commercial products. In addition, application of newer cosolvents is increasing to overcome some of these barriers. 

Microemulsions, and Lipid-Based Drug Delivery Systems for Drug Solubilization and Delivery—Part I Parenteral Applications... 

In addition to the concepts such as emulsions, submicron emulsions, and microemulsions introduced in Chapter 10 (Part I Parenteral Applications), the following concepts and background information are important for oral formulations. 

As mentioned, hydrolysis is the other important mechanism by which some lipids (glycerides and phosphoglycerides) degrade and can lead to a reduction in pH due to liberation of free fatty acids this was discussed in Chapter 10 (Part I Parenteral Application). This phenomenon is less important for oral formulations when compared to parenteral products, since the former generally have low amounts of water in the formulation. Hydrolysis could occur on storage if water is absorbed from or through the gelatin shell. 

Historically, the administration of crystalline APIs has mainly found use in parenteral applications associated with intramuscular and subcutaneous injections as well as topical applications of suspensions containing micronized APIs. Commercially marketed pharmaceuticals categorized as suspensions for parenteral administration are illustrated in Table 17.3. Many of these products utilize drug substance size reduction in order to promote dissolution following administration. The degree... 

Drug Solubilization and Delivery-Part I Parenteral Applications. 195... 

ME systems intended for parenteral application have to be formulated using nontoxic and biocompatible ingredients. The o/w ME systems would be suitable to improve the solubility of poorly water soluble drug molecules whereas w/o ME systems would be best suited for optimizing the delivery of hydrophilic drug molecules that are susceptible to the harsh GI conditions. Moreover, w/o systems can serve to prolong the release and mask any potential tissue irritation and site toxicity that are caused by intramuscular (i.m.) administration of hydrophilic drug molecules. 

Jahnke, M. and Kuhn, K.D. (2003), Use of Hazard Analysis and Critical Control Points (HACCP) Risk Assessments on a Medical Device for Parenteral Application, PDA Journal of Pharmaceutical Science and Technology, 57(1), January/February. 

In aqueous alcoholic solutions, it very readily solubilizes essential oils. Aqueous solutions of hydrophobic drugs (e.g. miconazole, hexetidine, clotrimazole, benzocaine) can also be prepared with Cremophor EL. Cremophor EL has also been used as a solubilizing agent for drugs like cyclosporin A, paclitaxel, and cisplatin. Cremophor LLP is manufactured by purifying Cremophor EL and is therefore suitable for parenteral applications, e.g. Taxol preparations. In oral formulations, the taste of polyoxyl 35 castor oil (Cremophor EL) can be masked by a banana flavor. 

Other lipid compositions with synthetic lipids, hydrogenated SPC (HSPC) and PEG-modified phospholipids are often used, especially for liposome formulations intended for parenteral applications use (long circulating or stealth liposomes) (41). Several analytical methods to follow loss of lipids during the preparation steps are available. Radioactively labeled lipids ( H-DPPC, C-DPPC) or cholesterol ( H-cholesterol) or H-cholesteryl hexadecyl ether (NEN Life Science Products, Boston, MA, USA) or lipophilic fluorescence dyes (e.g. lipophilic BODIPy derivatives. Molecular Probes) are added at appropriate amounts to the initial lipid mixtures. 

Plastics are used in virtually every pharmaceutical application (oral, topical, ophlthalmic, parenteral applications), either as a single material or in combination with other materials, as coatings or laminations. 

The scientific goal of Working Group 1 (a) has been the development and updating of quality control methods to assure safety of Tc pharmaceuticals for parenteral application in nuclear medicine. Scientific institutions in 12 European countries have contributed their experience and results for comparison of the available methods. The Eu-... 

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