Pharmaceutical applications studies

The final part, on pharmaceutical applications, consists of five chapters and includes topics such as drugs at liquid interfaces, NMR studies, and drugs and gene delivery. 

Thermodynamics of adsorption at liquid interfaces has been well established [22-24]. Of particular interest in view of biochemical and pharmaceutical applications is the adsorption of ionic substances, as many of biologically active compounds are ionic under the physiological conditions. For studying the adsorption of ionic components at the liquid-liquid interface, the polarized liquid-liquid interface is advantageous in that the adsorption of ionic components can be examined by strictly controlling the electrical state of the interface, which is in contrast to the adsorption studies at the air-water or nonpolar oil-water interfaces [25]. 

Recently, many studies have focused on self-assembled biodegradable nanoparticles for biomedical and pharmaceutical applications. Nanoparticles fabricated by the self-assembly of amphiphilic block copolymers or hydrophobically modified polymers have been explored as drug carrier systems. In general, these amphiphilic copolymers consisting of hydrophilic and hydrophobic segments are capable of forming polymeric structures in aqueous solutions via hydrophobic interactions. These self-assembled nanoparticles are composed of an inner core of hydrophobic moieties and an outer shell of hydrophilic groups [35, 36]. 

NIRSy stems, Inc., Application Note, Following the progress of pharmaceutical mixing studies using near-infrared spectroscopy, Silver Spring, Md. 

The study of fine particles in pharmaceutical applications involves a number of different techniques. Micromeritic investigations involve surface areas, particle sizes and their distributions, the nature of solid surfaces, and particle shapes [4]. Scientists working in this field realize that a number of techniques are necessary to fully investigate a system and that an interdisciplinary approach is essential. This ability to correlate data from different techniques allows a more thorough understanding of the system, process, or problem being investigated. 

One can conclude that PVA hydrogels represent an efficient encapsulation vehicle for the studied porphyrins, both water soluble and non-water soluble. Their biocompatible, biodegradable, non-toxic, and non-carcinogenic nature makes them especially effective for pharmaceutical applications, but also for environmental uses, such as advanced wastewater... 

Pristine CNTs are hydrophobic and cause a lack of solubility in biological aqueous fluids such as blood. The poor solubility of CNTs in blood stream poses a major challenge to in vivo studies making behavior of CNTs difficult to predict and control (Kam et al., 2005 Zheng et al., 2003a, b). Therefore, modification of CNT surface to introduce hydrophilic, functional groups has been utilized in pharmaceutical applications (Lacerda et al., 2006). However, insufficient in vivo evaluation of both pristine and surface-modified CNTs has been performed to answer essential questions on CNT toxicology. Additional in vivo studies also required to devise the best method of administration, means of uptake, metabolism, and elimination of CNTs. The in vivo studies on CNTs performed to date are presented in Table 12.2. 

The effects of size surface area, shape, purity method of synthesis, charge, surface coating, functionalized groups, and aggregation need to be carefully considered when assessing potential risks of CNT toxicity. Toxicology studies on CNTs should be accompanied by improved control in manufacturing and improved analysis before CNTs can be successfully used for pharmaceutical applications. 

In an overview on CE for pharmaceutical applications, Altria describes the analysis of ionic salts, organic acids, and also water purity, which may have deleterious effects on synthetic processes. In her review, Natishan " also included indirect UV detection when performing pharmacokinetic studies. 

J.O. Waltersson, Factorial designs in pharmaceutical preformulation studies. I. Evaluation of the application of factorial designs to a stability study of dmgs in suspension form. Act. Pharm. Suec., 23 (1986) 129. 

Studies on the potential of the electrochemical approach to pyrazolotriazoles 117 showed that under the conditions of bicycle synthesis from 3-amino-4-hydrazonopyrazoles the N-l-unsubstituted triazole ring of 117 was further oxidized in a one-electron peak, followed by proton removal to yield the bis-(l,l )-2-phenylpyrazolo[3,4-i/][l,2,3]triazoles 118. This observation is significant, since in spite of pronounced pharmaceutical applications of pyrazoles, the redox characteristics of substituted pyrazoles have received limited attention (Scheme 13) <2001MI1022>. 

Strong Public Health Protection Information on pharmaceutical development studies in new drug applications is generally limited and varies from application to application. This creates an uncertain environment and curtails FDA reviewers ability to make risk-based decisions and inhibits their ability to recognize and assess how quality was built in. Risk communication between review and inspection staff is also inhibited. Appropriate pharmaceutical development information can improve public health by improving FDA s risk-based decisions and by facilitating continuous improvement. 

Jenke [73] studied the extractabihty of aniline, diphenylguanidine, dedenzyl-amine, and triisopropanolamine from a synthetic polyisoprene rubber similar to the material used in pharmaceutical applications. Rubber samples were autoclaved (121 °C) in contact with water or NaCl 0.9% solution for lh.Table 33 presents the concentration of each compound in solution after the extraction procedure using 2g rubber material. Extraction profiles ranged between 1.64 and 3.73 mg/L, with the exception of diphenylguanidine, whose extraction yield reached 11.76 mg/L. 

In studies of analogs of the redox cofactor pyrroloquinoline quinone (PQQ), synthetic efforts have focused initially on isosteric, isomeric structures that reflect on important mechanisms of electron-transfer catalysis mediated by PQQ. These studies provide insight into the choice of PQQ as an electron-transfer catalyst in nature, and bear directly on pharmaceutical applications of this vitamin-like nutritional factor. 

Several complexes have been tested for potential pharmaceutical applications and some of them have been introduced into practice.84,126 Isolation of antibiotics of boron complex type (Section 24.3.3.2) and results obtained with carboxyborane complexes that are analogues of amino acids (Section 24.2.2) are likely to stimulate further studies. Quite a few boron complexes have found application in 10B neutron capture therapy based on the 10B(n, a)7Li nuclear reaction.84,126,172... 

In addition to the binding constant and safety considerations, economics, and quality control issues also play a role in considering which ligands to use. Because of the difLculty in selectively derivatizing a speciLc hydroxyl or family of hydroxyls, most modiLed CDs of pharmaceutical interest are likely to be complex mixtures (Stella and Rajewski, 1997). Methods to characterize these mixtures, therefore, need to be in place to assure lot-to-lot reproducibility. The costs of acute and chronic safety studies required to evaluate any new CD derivatives are very high, and this prohibits them from being widely evaluated for pharmaceutical applications. 

---