Excipient Binder

To demonstrate the ability to evaluate intersample variations, an over-the-counter (OTC) pain relief medication from two different manufacturers was compared. The samples contain three APIs each acetaminophen, aspirin and caffeine. Pure acetaminophen, aspirin and caffeine samples are obtained in either tablet form or powder compact and included within the same FOV as the tablets to provide simultaneous reference materials for the tablet samples. The tablets and pure components were arranged as shown in Plate 8.1a. Measurements on all samples were collected simultaneously. Tablet A samples from one manufacturer have a reported label concentration of 37%, 37%, and 10%, for the three API components, respectively. Tablet B samples from the second manufacturer contain the same three APIs, at label concentrations of 39%, 39%, and 10 %, respectively. In addition to these samples, tablet C samples are included in the array of tablets. These samples contain only acetaminophen as the API with a reported label concentration of 79%, and are made by the manufacturer who produces tablet A. The remaining mass of all three tablet types represents the excipient (binder, disintegrant, and lubricant) materials. 

The concentrations of the active ingredients as reported from the manufacturer s label are 37% acetaminophen, 37% aspirin, and 10 % caffeine. The remainder of the tablet mass represents the excipient (binder, disintegrant, and lubricant) materials. Pure acetaminophen, aspirin and caffeine samples are obtained in either tablet form or powder compact and used to obtain reference specua of pure components. 

A simple foam generation apparatus is used to incorporate air into a conventional water-soluble polymeric excipients binder such as METHOCEL hypromeUose (hydroxypropyl methylcellulose). The resulting foam has a consistency like shaving cream. HypromeUose polymers are ideal candidates for this technology because they are excellent film formers and create exceptionally stable foams. 

In many pharmaceutical products, the formulated end products contain dyes, additives, excipients, binders, active materials, and an identification mark. The active materials are often crystalline with a high Raman-scattering cross section, whereas the excipients generally have a lower Raman cross section and many exhibit low levels of fluorescence. In addition, the dyes and the identification mark tend to fluoresce under visible excitation. Thus, FT-Raman spectroscopy has proved itself in formulated product analysis, whereas dispersive Raman spectroscopy with visible excitation can be successfully employed for monitoring active-material manufacturing. 

Common excipients diluents, disintegrators, binders, and lubricants (gUdants). 

The Cadila system [13] has been designed to formulate tablets for drugs based on their physical (solubility, hydroscopicity, etc), chemical (functional groups), and biologically interrelated (dissolution rate) properties. The system first identifies the desirable properties for optimum compatibility with the drug, selects those excipients that have the required properties, and then recommends proportions based on the assumption that all tablet formulations comprise at least one binder, one disintegrant, and one lubricant. Other... 

Incompatibilities have also been observed in solid dosage forms. A typical tablet contain binders, disin-tegrants, lubricants and fillers. Compatibility screening for a new drug should consider two or more excipients from each class. Serajuddin et al. have developed a drug-excipient compatibility screening model to predict interactions of drug substances with excipients [49],... 

The USP/NF provides a listing of excipients by categories in a table according to the function of the excipient in a dosage form, such as tablet binder, disintegrant, and such. An excellent reference for excipient information is the APA s Handbook of Pharmaceutical Excipients (1994). 

Excipients are sub-divided into various functional classifications, depending on the role that they are intended to play in the resultant formulation, for example, fillers, disintegrants, binders, lubricants and glidants. An added complexity is the fact that certain excipients can have different functional roles in different formulation types. Thus, lactose is widely used as a filler or diluent in solid oral dosage forms, for example, tablets and capsules [2] and as a carrier for inhalation products [3]. 

Hartauer et al. [58] reported that peroxide residues in povidone (binder) and crospovidone (disintegrant) were attributable to the formation of the A-oxide oxidation product of raloxifene. The authors correlated residual levels of peroxide in the excipients with A-oxide formation and thereby gained understanding of the degradation mechanism. A radical-initiated oxidation mechanism would be expected to show a typical S -shaped autocatalytic curve, whereas these curves showed fickian kinetics that is, rapid initial formation of the A-oxide followed by a plateauing of the rate, with consumption of the peroxides, leading to a slowing of the reaction rate. 

Huang et al. [59] evaluated some common excipients for residual levels of hydrogen peroxide. They found levels of H2O2 in the range 0-244 ppm, but perhaps of more concern, they showed quite pronounced differences between different batches of the same vendor and between different vendors of the same excipient. For example, although there is some variability of residual peroxide levels in PEG 400 (polyethylene glycol) from vendor B (5-16 ppm), the differences were small, in contrast with those seen from vendor C (2-59 ppm). Similarly, the differences in residual peroxide in the binder PVP (polyvinyl pyroli-done) from two different vendors were quite marked (73 vs 244 ppm). Formulations optimised for excipients from specific sources could well be sub-optimal if the... 

In this section a study is described in which tablets prepared with binary blends of a filler-binder and a disintegrant are evaluated, with respect to their physical stability after storage under tropical conditions. With the results of this study a selection from the excipients can be made, which are suitable for use in tropical countries. Tablet formulations can be developed with the thus selected excipients. 

Also the influence of the adjustable variables (disintegrant concentration and storage temperature and relative humidity), on the SIR of disintegration time (SIR(D)) was calculated for each combination of disintegrant and filler-binder. This was expressed as in equation (10). The coefficients of the equations for the different combinations of excipients are given in Table 8.9. 

Native starches are used as disintegrants, diluents, and wet binders. However, their poor flow and high lubricant sensitivity make them less favorable in direct compression. Different chemical, mechanical, and physical modifications of native starches have been used to improve both their direct compression and controlled-release properties (Sanghvi, 1993 van Aerde and Remon, 1988). Schinzinger and Schmidt (2005) used potato starch as an excipient and compared its granulating behavior with a-lactose-monohydrate and di-calcium phosphate anhydrous in a laboratory fluidized bed granulator using statistical methods. 

Polyelectrolytes (most notably ionic cellulose derivatives and crosslinked polyacid powders) are also commonly used as matrices, binders and excipients in oral controlled release compositions. In these applications, the polyelectrolytes provide hydrophilicity and pH sensitivity to tablet dosage forms. Acidic polyelectrolytes dissociate and swell (or dissolve) at high pH values whereas basic polyelectrolytes (for instance, polyamines) become protonated and swell at low pH. In either case, swelling results in increased permeability [290], thereby allowing an incorporated drug to be released. 

The batch size ranged from 3.75 up to 60 kg. To obtain precise scale-up measurements, the excipients which were used belonged to identical lots of primary material [10% (W/W) corn starch, 4% (W/W) polyvinylpyrrolidone as binder, and 86% (W/W) lactose]. As can be seen from Figure 4, the amount of granulating liquid is linearly dependent on the batch size. During the scale-up exercise, the rate of addition of the granulation liquid was enhanced in proportion to the larger batch size. Thus the power profile, which was plotted... 

Dry blending of the primary powder material, i.e., active substance and auxiliary substances in a mixer. Preference should be given to demineralized water as granulating liquid and the excipients and the drug should show relatively low water solubility with the exception of the binder. The binder should be preferably added in a dry state as part of the powder components. 

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