Excipients in parenteral formulations: selection considerations and effective utilization with small molecules and biologics

Excipients form a major component of pharmaceutical formulations and are classified as any ingredient other than the active ingredient which is included within the product formulation to improve drug product performance. Functional uses of excipients include improving solubility and stability, safety and efficacy, as bulking agents in lyophilized formulations, tonicity agents, and aiding in controlled or prolonged drug delivery. Parenteral formulations are sterile, pyrogen-free; free of particulate matter and by-pass the body’s natural defense mechanisms. Excipients may demonstrate a synergistic effect when combined with an active ingredient but may also lead to unwanted reactions with the drugs and packaging components. Ideal excipients are required to be considered safe, inert and multifunctional. Contrary to the past, safety of excipients needs to be well established in order for their use in the pharmaceutical formulations. Therefore, careful consideration should be given while selecting an excipient. This review article provides an overview of the excipients used exclusively in small molecule and biological parenteral products including solutions, suspensions, and lyophilized formulations, information on the possible drug-excipient and drug-packaging interactions and the regulatory requirements for the use of pharmaceutical excipients. The readers will be able to have a comprehensive understanding of the excipients used in parenteral formulations.     

Electrical and Thermal Properties of Twin-Screw Extruded Multiwalled Carbon Nanotube/Epoxy Composites

This paper presents the experimental results of dispersing multiwalled carbon nanotubes (MWNTs) into epoxy (space grade structural adhesive) nanocomposites using co-rotating twin screw extrusion process. Two sets of specimens were prepared; set 1 with ultrasonication for predispersing MWNT before extrusion and set 2 direct dispersion of MWNT in the extruder. MWNT was loaded up to 8 vol.% in both the sets. The specimens were characterized for room temperature volume and surface resistivities as per ASTM D257 using Keithley Model 6517 and for thermal conductivity in the temperature range ?50 to 150 °C as per ASTM E 1530 using Thermal Conductivity Instrument (TCI) 2022 SX211. The volume resistivity of sets 1 and 2 decreased to an extent of 10¹¹ and 10⁹ respectively. The surface resistivity drop was of the order of 10⁹ for both the sets. These drops corresponded to the maximum MWNT loading of 8 vol.%. Electrical conductivity values of the specimens were fitted into the Power Law Model to evaluate the critical exponent. Both sets 1 and 2 showed increase in thermal conductivity with increase in temperature in the testing range. Thermal conductivity increased with increase in filler loading and the maximum increase was 60% at 150 °C in case of 8 vol.% MWNT nanocomposites for set 1. The corresponding value for the set 2 was 25%. Thermal conductivity values were predicted using Lewis Nielson model. DSC of the specimens showed increase in glass transition temperature with increase in filler loading. The dispersion of the nanofillers was studied using SEM and the surface morphology using AFM.     

A risk management approach to safety assessment of trenchless technologies for culvert rehabilitation

Proper functioning of culverts is not only critical to protecting the transportation system from flooding but also critical to maintaining the expected service life of the overall transportation system. During the service life of culverts, they deteriorate due to many reasons such as corrosion caused by road salt, blockage by debris and sediment, poor construction techniques, etc. Trenchless technologies have been used by several State Departments of Transportation (DOTs) to rehabilitate deteriorated drainage structures without disrupting the traffic and within a relatively short span of time. These technologies provide many benefits in terms of cost, time, quality, and expected service life. However, the safety aspects of these techniques have not been discussed and documented in detail probably due to the complexity and the lack of safety standards and specifications directly associated with the techniques. This paper discusses the application of a risk assessment framework to assess potential safety issues of currently available trenchless technologies for culvert rehabilitation. The findings of the study will provide additional information to improve the decision making process in selecting and planning culvert rehabilitation projects.     

Heat-induced Maillard reaction of the tripeptide IPP and ribose: Structural characterization and implication on bioactivity

Maillard reaction products (MRPs) were prepared from aqueous model mixtures containing 60 g L^? 1 ribose and 30 g L^? 1 of the bioactive tripeptide IPP (Ile-Pro-Pro), heated at 98 °C. MRP and associated reactions with changes in IPP were observed within one hour of heat-treatment. The pH of MRPs decreased significantly during the heat treatment of IPP–ribose mixtures from 9.0 to 7.6 after one hour. The amino group content, IPP and ribose concentration decreased significantly during heat treatment. The fluorescence intensity of the IPP–ribose MRPs reached the maximum within 2 h. Modification of the UV/vis spectra for IPP–ribose MRPs was mainly due to a condensation reaction of IPP with ribose. Compounds with molecular weight between 300 and 650 Da were dominant while compounds smaller than 250 Da were also produced during the reactions, as characterized by size exclusion chromatography. Mass spectrometry revealed that IPP was conjugated to ribose at the N-terminal (m/z of 458.3) upon heat-treatment. The presence of ribose also promoted peptide degradation to dehydrated IP (m/z of 211.1). IPP–ribose MRPs lost the known angiotensin-I-converting enzyme (ACE) inhibitory activity of IPP; however, strong antioxidant properties were detected.     

Measuring cellular structure at submicrometer scale with lightscattering spectroscopy

We present a novel instrument for imaging the angular distributions of light backscattered by biological cells and tissues. The intensities in different regions of the image are due to scatterers of different sizes. We exploit this to study scattering from particles smaller than the wavelength of light used, even when they are mixed with larger particles. We show that the scattering from subcellular structure in both normal and cancerous human cells is best fitted to inverse power-law distributions for the sizes of the scattering objects, and propose that the distribution of scattering objects may be different in normal versus cancerous cells     

Binding of organic anions by synthetic supramolecular metallopores with internal Mg2+-aspartate complexes

We report that cation-selective transmembrane pores formed by synthetic p-octiphenyl beta barrels with internal aspartate residues can be transformed into anion-permeable metallopores with internal Mg(2+)-aspartate complexes. These metallopores are shown to be useful for fluorimetric sensing of a broad variety of organic anions of biological relevance such as phytate, heparin, thiamine phosphates, and adenosine triphosphate. The negligible flippase activity measurable for Mg(2+)-free pores indicates that transmembrane p-octiphenyl beta barrels do not disturb the lipid bilayer suprastructure, in other words, they form barrel-stave rather than toroidal pores.     

Secure electronic markets for private information

Technological advances in the collection, storage, and analysis of data have increased the ease with which businesses can make profitable use of information about individuals. Some of this information is private, and individuals are simultaneously becoming more aware of the value of the information and how the loss of control over this information impacts their personal privacy. As a partial solution to these concerns, this paper presents a mechanism that serves two purposes. The first enables the use of private, numerical data in the answering of queries while simultaneously providing a security feature that protects the data owners from a loss of privacy that could result from an unauthorized access. The second develops a compensation model for the use of the data that allows individuals to dynamically redefine their security requirements. The compensation model is built on the information-security mechanism to create the foundation of a market for private information. This paper illustrates how compensation models like the one presented here could be used in a self-regulating market for private information. Additionally, the compensation component of an intermediated market for private information is developed and extensively analyzed. Finally, this paper provides insights and draws several important conclusions on markets for private information.