Imports/importers excipients

In many products it seems highly probable that there exists a narrow range of optimum moisture contents that should be maintained. More specifically, the effect of moisture on MCC-containing tablets has been the subject of an investigation that demonstrates the sensitivity of this important excipient to moisture content [10]. These researchers found that differences exist in both the cohesive nature and the moisture content to two commercial brands of MCC. A very useful report on the equilibrium moisture content of some 30 excipients has been compiled by a collaborative group of workers from several pharmaceutical companies and appears in the Handbook of Pharmaceutical Excipients [11,12],... 

Second, there is the possibility that the drug or some important excipients may interact with constituents of fecal matter or material fluid present in the rectum. This may reduce the drug absorption and diminish effectiveness. 

Formulation Clinical use Active ingredients and important excipients... 

CeUnlose ethers are widely nsed as important excipients for designing matrix tablets. On contact with water, the cellulose ether swells and forms a hydrogel layer around the dry core of the tablet. The hydrogel presents a diffusional barrier for water molecules penetrating into the polymer matrix and the drug molecules being released. ... 

Microemulsions are transparent systems of two immiscible fluids, stabilized by an interfacial film of surfactant or a mixture of surfactants, frequently in combination with a cosurfactant. These systems could be classified as water-in-oil, bicontinuous, or oil-in-water type depending on their microstructure, which is influenced by their physicochemical properties and the extent of their ingredients. - SMEDDSs form transparent microemulsions with a droplet size of less than 50 nm. Oil is the most important excipient in SMEDDSs because it can facilitate self-emulsification and increase the fraction of lipophilic drug transported through the intestinal lymphatic system, thereby increasing absorption from the gastrointestinal tract. Long-chain and medium-chain... 

Over the past few years, increasing attention has been given to drug delivery using nanoparticles and micelles. Positively charged nanoparticles have been known as important excipients in different pharmaceutical... 

The most important excipients in parenteral nutrition solutions are emulsifying agents. Lecithin and phosphatides are mostly used. The emulsifying capacity of phosphatides correlates with their ionisation rate and thereby the pH of the emulsion. The pH also influences the stability of the hpid droplets [58]. If the pH decreases below 3, the droplet surfaces are no longer negatively charged and the droplets coalesce (see Sect. 18.4.1). If necessary, the pH is adjusted with an aqueous solution of sodium hydroxide or hydrochloric acid. 

Although, the oil phase and the emulsifiers are the most important excipients in the design process of a specific nanoemulsion formulation, additives are further needed to adjust to physiological pH and tonicity, to protect nanoemulsions from oxidation and phase separation or drug degradation and sometimes from microbial contamination (preservatives) if nanoemulsion is intended for ocular administration. All ingredients used should be pharmaceutical grade materials. 

Local and state forensic laboratories generally do not engage ia excipient testing. Most provide quaUtative and quantitative analysis of the evidence to determine if an Ulegal substance is present and if so, the amount of the dmg present. The quantity of dmg seized by the authorities may be important ia jurisdictions which give enhanced sentences for larger amounts of the pure dmg, or ia some cases the total weight on the dmg and diluent ia possession of the defendant. 

The selection of excipient ingredients is important. These must be both chemically and physically compatible with the dmg moiety and cannot negatively affect product stabihty or therapeutic performance, ie, bio avadabihty. A comprehensive hst of various types of excipient ingredients, with comment upon usage, is available (16). 

Comprehensive physicochemical characterization of any raw material is a crucial and multi-phased requirement for the selection and validation of that matter as a constituent of a product or part of the product development process (Morris et al., 1998). Such demand is especially important in the pharmaceutical industry because of the presence of several compounds assembled in a formulation, such as active substances and excipients, which highlights the importance of compatibility among them. Besides, variations in raw materials due to different sources, periods of extraction and various environmental factors may lead to failures in production and/or in the dosage form performance (Morris et al., 1998). Additionally, economic issues are also related to the need for investigating the physicochemical characteristics of raw materials since those features may determine the most adequate and low-cost material for specific procedures and dosage forms. 

When acidic or latent acidic excipients (anhydrides) are incorporated into the polymer to control erosion rate, the polymers become quite sensitive to moisture and heat and must be processed in a dry environment. A rigorous exclusion of moisture is particularly important with materials that are designed to erode in less than 24 hr. Such materials may contain up to 5 wt% of an acidic catalyst and are analogous to a "loaded gun" in that even the slightest amount of moisture will initiate hydrolysis at the elevated processing temperatures. ... 

It should again be emphasized that at the onset of a new drug program, there are only small amounts of drug substance at hand. One of the first tasks for the preformulation scientist is to establish the framework within which the first clinical batches can be formulated. To this end it is important to know with which common excipients the drug is compatible. Below, the distinction will be made between solid and liquid dosage forms. 

It is important for the formulator of a new drug substance to know with which excipients he can work and with which he cannot. Some pharmaceutical incompatibilities are known to the formulator, e.g., magnesium stearate/aspirin, and glucose/amines [53],... 

With transdermal dosage forms being of great importance of late, it is advisable to test for compatibilities with ointment excipients and with polymers (e.g., ethylvinyl polymer, if that is the desired barrier). 

Often these design criteria involve competitive requirements. What is best for meeting one criterion may be counterproductive in meeting another. For example, certain excipients such as the hydrophobic stearate lubricants are important for efficient manufacture, yet they have the potential to retard the release of drug from an immediate-release formulation. The design of a dosage form thus frequently requires the optimization of formulation and process variables in a way that best meets all design criteria. 

The dose of the drug and its solubility are important considerations in the design of the formulation. The amount and type of active ingredient influences capsule size and the nature and amount of excipients to be used in the formulation. Larger-dose drugs that must be granulated to produce tablets may be more easily direct-filled into hard shell capsules with proper choice of excipients. 

The moisture uptake models we have discussed have been concerned with pure components. The deliquescing material could be a drug substance or an excipient material. In pharmaceuticals, however, mixtures of materials are also important. One possible situation involves mixing nondeliquescing and deliquescing materials that are formed into a porous tablet or powder blend. The obvious question is, Do the models for pure components apply to porous heterogeneous materials For pure components we have assumed that the mass and heat limiting transport... 

Second, P-gp differs from other transporters in that it recognizes its substrates when dissolved in the lipid membrane [52], and not when dissolved in aqueous solution. The site of recognition and binding has been shown to be located in the membrane leaflet facing the cytosol [53, 54], This implies that the membrane concentration of the substrate, Csm, determines activation [57]. Since the nature of a molecular interaction is strongly influenced by the solvent, the lipid membrane must be taken into account as the solvent for the SAR analysis of P-gp. Under certain conditions, the effect of additional solvents or excipients (used to apply hydrophobic substrates or inhibitors) on the lipid membrane and/or on the transporter must also be considered. Lipophilicity of substrates has long been known to play an important role in P-gp-substrate interactions nevertheless, the correlation of the octanol/water partition coefficients with the concentration of half-maximum... 

The interaction between drug compounds and excipients, as these influence drug dissolution, can be successfully studied by means of reflectance spectroscopy. In one study concerning probucol and indomethacin, it was deduced that hydrogen bonding and van der Waals forces determined the physisorption between the active and the excipients in several model formulations [36]. Chemisorption forces were found to play only minor roles in these interactions. These studies indicated that surface catalytic effects could be important during the selection of formulation excipients. 

The topics of polymorphism and pseudopolymorphism dominate the majority of publications that deal with utilizing infrared spectroscopy for the physical characterization of pharmaceutical solids. Typically, in each of the publications, IR spectroscopy is only one technique used to characterize the various physical forms. It is important to realize that a multidisciplinary approach must be taken for the complete physical characterization of a pharmaceutical solid. Besides polymorphism, mid- and near-IR have been utilized for identity testing at the bulk and formulated product level, contaminant analysis, and drug-excipient interactions. A number of these applications will be highlighted within the next few sections. 

Plastic deformation is the permanent change in shape of a specimen due to applied stress. The onset of plastic deformation is seen as curvature in the stress—strain curve. Plastic deformation is important because it allows pharmaceutical excipients and drugs to establish large true areas of contact during compaction that can remain on decompression. In this way, good, intact, tablets can be prepared. 

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